ArticleLiterature Review

Oxidative Stress in the Pathogenesis of Preeclampsia

January 2000
Proceedings of The Society for Experimental Biology and Medicine 222(3):222-35

January 2000
222(3):222-35

DOI:10.1046/j.1525-1373.1999.d01-139.x

Source
PubMed

Authors:

The etiology and pathogenesis of the pregnancy syndrome preeclampsia remain poorly understood. There is substantial evidence to suggest that the diverse manifestations of preeclampsia, including altered vascular reactivity, vasospasm, and discrete pathology in many organ systems, are derived from pathologic changes within the maternal vascular endothelium. With the theme of endothelial cell dysfunction emphasized, this review focuses on the role of oxidative stress (an imbalance favoring oxidant over antioxidant forces) in the pathogenesis of preeclampsia. Data are summarized regarding 1) the role of the placenta in preeclampsia; 2) evidence and mechanisms of oxidative stress in the preeclampsia placenta; 3) markers of oxidative stress in the maternal circulation; and 4) the potential role of maternal dyslipidemia in generation of oxidative stress. A recurrent theme is that free radical reactions, promoted by "cross-talk" between the diseased placenta and maternal dyslipidemia, promote a vicious cycle of events that make cause and effect difficult to distinguish but likely contribute to the progression of preeclampsia.

Difference of Frap Levels Between Preeclamptic and Normotensive Women: A Cross-Sectional Analysis from a Tertiary Care Hospital, Pakistan

Article

Jul 2022

Objective: To determine the association between FRAP levels and preeclampsia Methodology: A case control study was conducted at Social Security Teaching Hospital Multan Road, Lahore between September 2019 March 2020. A total of 309 women were enrolled in the study using the non-probability convenience sampling technique. Women at 28 weeks or higher gestation, equal to or older than 18 years of age were included in the study. Those with a history of hypertensive issues before 20 weeks of gestation or other comorbidities were excluded from the study. For antioxidative analysis, the serum FRAP was measured using colorimetric assay. Patients sociodemographic, clinical, and reproductive history were recorded. For data analysis, SPSS version 24 was used and a p-value of 0.05 or less was considered as statistically significant. Results: Preeclampsia was found in 40 (13%) pregnant women in our study. The mean age + SD for the group with pre-eclampsia was 21.56 + 4.2 years while the mean age + SD for the normotensive group was 22.12 +5.6 years. The mean + SD FRAP levels were significantly higher in women with preeclampsia than the normotensive control group (p=0.01); 684.2 + 21.2 μmole/L in the preeclampsia group and 603.1 + 15.6 μmole/L in the control group. Conclusion: The FRAP levels were significantly higher in women with preeclampsia than the normotensive women indicating a correlation between high oxidative stress and risk of developing threatening pregnancy related issues. Keywords: antioxidant, FRAP, gestational, oxidative stress, preeclampsia

Preeklampsili Gebelerde Serum Dinamik Tiyol-Disülfit Dengesinin Değerlendirilmesi ve TNF-α ve Düşük Doğum Ağırlığı ile İlişkisi

Article

Dec 2023

Amaç: Preeklampsi gebeliğin 20. Haftasından sonra ortaya çıkan ve hipertansiyon ile karakterize bir gebelik komplilkasyonudur. Hastalığın patogenezinde uterovasküler yetmezliğe bağlı gelişen doku iskemisi ve buna ortaya çıkan oksidatif stres rol oynar. Vücutta oksidatif dengenin korunmasında dinamik tiyol-disülfit dengesi önemli bir rol oynar. Bu çalışmada preekalmpsili gebelerde serum dinamik tiyol-disülfit dengesi ve TNF-α ve düşük doğum ağırlığı ile ilişkisinin belirlenmesi amaçlanmıştır. Yöntemler: Preeklampsi tanısı almış 30 gebe ile yaş ve cinsiyet olarak eşitlenmiş 30 sağlıklı gebe kontrol grubu olarak çalışmaya dahil edildi. Tüm gebelerden 2.veya 3. Trimesterlerde sabah açlık kanları toplandı. Tüm örnekler 1500 x g'de 10 dakika santrifüj edildikten sonra serum örnekleri porsiyonlara ayrıldı ve -80 °C'de saklandı. Serum total tiyol ile native tiyol düzeyler kolorimetrk yöntemle otoanalizörde ölçüldü ve disülft değerleri “disülfit miktarı= (Total Tiyol – Native Tiyol)/2” formülü ile hesaplandı. Serum TNF-α düzeyleri ise ELISA yöntem ile ölçüldü. Bulgular: Preeklampsili gebelerde sistolik ve diyastolik kan basınçları kontrol grubuna göre anlamlı derecede yüksekti (p

A Novel Dual-Function Redox Modulator Relieves Oxidative Stress and Anti-Angiogenic Response in Placental Villus Explant Exposed to Hypoxia-Relevance for Preeclampsia Therapy

Article

Full-text available

Sep 2023

Background: Preeclampsia (PE) is a severe, life-threatening complication during pregnancy (~5-7%), and no causative treatment is available. Early aberrant spiral artery remodeling is associated with placental stress and the release of oxygen radicals and other reactive oxygen species (ROS) in the placenta. This precedes the production of anti-angiogenic factors, which ultimately leads to endothelial and trophoblast damage and the key features of PE. We tested whether a novel dual-function redox modulator-AKT-1005-can effectively reduce placental oxidative stress and alleviate PE symptoms in vitro. Method: Isolated human villous explants were exposed to hypoxia and assessed to determine whether improving cell-redox function with AKT-1005 diminished ROS production, mitochondrial stress, production of the transcription factor HIF1A, and downstream anti-angiogenic responses (i.e., sFLT1, sEng production). MitoTEMPO was used as a reference antioxidant. Results: In our villous explant assays, pretreatment with AKT-1005 reduced mitochondrial-derived ROS production, reduced HIF-1A, sFLT1, and sEng protein expression, while increasing VEGF in hypoxia-exposed villous trophoblast cells, with better efficiency than MitoTEMPO. In addition, AKT-1005 improved mitochondrial electron chain enzyme activity in the stressed explant culture. Conclusions: The redox modulator AKT-1005 has the potential to intervene with oxidative stress and can be efficacious for PE therapy. Future studies are underway to assess the in vivo efficacy of HMP.

Preeclampsia Affects Lipid Metabolism and HDL Function in Mothers and Their Offspring

Article

Full-text available

Mar 2023

Preeclampsia (PE) is linked to an overall increased cardiovascular risk for both the mother and child. Functional impairment of high-density lipoproteins (HDL) may contribute to the excess cardiovascular risk associated with PE. In this study, we investigated the effects of PE on maternal and neonatal lipid metabolism, and the parameters of HDL composition and function. The study cohort included 32 normotensive pregnant women, 18 women diagnosed with early-onset PE, and 14 women with late-onset PE. In mothers, early-and late-onset PE was associated with atherogenic dyslipidemia, characterized by high plasma triglycerides and low HDL-cholesterol levels. We observed a shift from large HDL to smaller HDL subclasses in early-onset PE, which was associated with an increased plasma antioxidant capacity in mothers. PE was further associated with markedly increased levels of HDL-associated apolipoprotein (apo) C-II in mothers, and linked to the triglyceride content of HDL. In neonates of early-onset PE, total cholesterol levels were increased, whereas HDL cholesterol efflux capacity was markedly reduced in neonates from late-onset PE. In conclusion, early-and late-onset PE profoundly affect maternal lipid metabolism, potentially contributing to disease manifestation and increased cardiovascular risk later in life. PE is also associated with changes in neonatal HDL composition and function, demonstrating that complications of pregnancy affect neonatal lipoprotein metabolism.

Heat Shock Proteins (HSP) in Cellular Communication and Signaling

Book

Jan 2023

Cerebrovascular disease is an important cause of global morbidity and mortality. Inflammatory processes have been implicated in macro-vascular disease and has an important role in the development of intracranial atherosclerosis, plaque progression, and the rupture of brain aneurysms and ischemic stroke. Heat shock protein 27 (HSP27) is an intracellular chaperone that is expressed by many cell types, including cardiac myocytes and endothelial cells. Its expression is increased in response to cellular stress which includes oxidative stress. Studies have shown that in the normal brain, expression of HSP27 is low, but increasing the expression of HSP27 can protect against subsequent ischemia by stabilizing the cytoskeleton and increasing glutathione levels, inhibiting apoptosis-inducing factors, and reducing pro-inflammatory cytokines. HSP27 protects against cell damage in various human disorders in which reactive oxygen species are involved, including stroke. It mediates its neuroprotective signaling pathway by suppressing apoptosis, oxidative stress, and the inflammatory response to cell injury. HSP27 effects nuclear factor kappa B (NF-kB) activation and is considered to have anti-inflammatory effects. The effects of HSP27 have led to the proposal that it is a biomarker in the pathophysiological status of cerebrovascular diseases and as a therapeutic target after cerebrovascular disorder. This narrative review has revealed a potential relationship between HSP27 and cerebrovascular disease.

Biological Repercussions of HSP60’s Moonlight Properties in Female Reproduction

Chapter

Jan 2023

Heat shock protein 60 (HSP60) is highly conserved in evolution, from bacteria to animals. Its first described function was to assist the folding and refolding of denatured proteins, in association with HSP10. HSP60 was found mainly in mitochondria, but it can also be found in the cytosol, plasma membrane, peroxisomes, endoplasmic reticulum and blood. Apparently, the presence of the HSP60 in different cellular compartments is related to its mitochondrial import signal but also to its conformational structure. Besides protein folding, HSP60 was later recognised as a moonlighting protein, with multiple biological roles depending on its cellular location, the molecules with which it interacts, its oligomeric form and whether it is in its native or mature state, participating in multiple cellular processes, such as apoptosis, oxidative stress, immune alerting, senescence and steroidogenesis. Its participation is of relevance in the female reproductive system, given the importance for the general health and well-being during pregnancy and delivery, and because many clinical complications during pregnancy are related to several of the cellular processes mentioned above. Even more, several studies have found high levels of HSP60 in serum of pregnant women with different clinical complications, suggesting that HSP60 is playing a role in these clinical complications. Further research on the molecular and biochemical basis could explain whether the HSP60 participates with or without the signal peptide in the different cellular locations, or if the oligomeric conformation is responsible for specific activities, and whether they are related to the mechanism that translocates it from mitochondria to the cytosol or outside the cells. Therefore, this review aims to describe the moonlighting properties of HSP60 and its relationship with the female reproductive system in the processes mentioned above, highlighting the areas that require more focus to have a clear perspective of HSP60’s relevance in the female reproductive health field.

Puerariae lobatae Radix Alleviates Pre-Eclampsia by Remodeling Gut Microbiota and Protecting the Gut and Placental Barriers

Article

Full-text available

Nov 2022

Pre-eclampsia (PE) is a serious pregnancy complication, and gut dysbiosis is an important cause of it. Puerariae lobatae Radix (PLR) is a medicine and food homologous species; however, its effect on PE is unclear. This study aimed to investigate the efficacy of PLR in alleviating PE and its mechanisms. We used an NG-nitro-L-arginine methyl ester (L-NAME)-induced PE mouse model to examine the efficacy of preventive and therapeutic PLR supplementation. The results showed that both PLR interventions alleviated hypertension and proteinuria, increased fetal and placental weights, and elevated the levels of VEGF and PlGF. Moreover, PLR protected the placenta from oxidative stress via activating the Nrf2/HO-1/NQO1 pathway and mitigated placental damage by increasing intestinal barrier markers (ZO-1, Occludin, and Claudin-1) expression and reducing lipopolysaccharide leakage. Notably, preventive PLR administration corrected gut dysbiosis in PE mice, as evidenced by the increased abundance and positive interactions of beneficial bacteria including Bifidobacterium, Blautia, and Turicibacter. Fecal microbiota transplantation confirmed that the gut microbiota partially mediated the beneficial effects of PLR on PE. Our findings revealed that modulating the gut microbiota is an effective strategy for the treatment of PE and highlighted that PLR might be used as an intestinal nutrient supplement in PE patients.

Coenzyme A Restriction as a Factor Underlying Pre-Eclampsia with Polycystic Ovary Syndrome as a Risk Factor

Article

Full-text available

Mar 2022
INT J MOL SCI

Pre-eclampsia is the most common pregnancy complication affecting 1 in 20 pregnancies, characterized by high blood pressure and signs of organ damage, most often to the liver and kidneys. Metabolic network analysis of published lipidomic data points to a shortage of Coenzyme A (CoA). Gene expression profile data reveal alterations to many areas of metabolism and, crucially, to conflicting cellular regulatory mechanisms arising from the overproduction of signalling lipids driven by CoA limitation. Adverse feedback loops appear, forming sphingosine-1-phosphate (a cause of hypertension, hypoxia and inflammation), cytotoxic isoketovaleric acid (inducing acidosis and organ damage) and a thrombogenic lysophosphatidyl serine. These also induce mitochondrial and oxidative stress, leading to untimely apoptosis, which is possibly the cause of CoA restriction. This work provides a molecular basis for the signs of pre-eclampsia, why polycystic ovary syndrome is a risk factor and what might be done to treat and reduce the risk of disease.

Effect of Synbiotic Supplementation on Maternal and Neonatal Outcomes in Pregnant Women With Pre-eclampsia: Study Protocol for a Triple Blind Randomized Controlled Clinical Trial

Article

Full-text available

Jul 2023

Objectives: Background: Preeclampsia is one of the main causes of premature birth, growth restriction, and intrauterine death of fetus. Probiotics has the potential to modulate inflammatory and oxidative stress biomarkers that implicated in the pathophysiology of preeclampsia. The aim of the present study is to establish the impact of synbiotic supplements, comprising of probiotic and prebiotic fructooligosaccharide, in comparison to placebo, on the maternal and neonatal outcome outcomes in women afflicted with mild preeclampsia. Methods: This is a study protocol of a randomized, controlled, phase 3, triple-blind, randomized clinical trial. The classification is based on the gestational age at the time of diagnosis of mild preeclampsia (early-onset or late-onset preeclampsia). Participants will be 128 pregnant women with mild pre-eclampsia (systolic blood pressure between 140-160 mm Hg or diastolic blood pressure between 90-110 mm Hg, along with other preeclampsia symptoms). Participants will divide into two intervention and control groups using a 1:1 random allocation ratio randomly. They will receive one oral capsule (the concentration of 109 CFU) or placebo daily from admission until delivery. Primary outcomes included mean systolic and diastolic blood pressure, mean gestational age from diagnosis to delivery, and mean birth weight. Also, secondary outcomes included proteinuria, serum creatinine level, the incidence of severe PE, the use of antihypertensive drugs, the rate of natural delivery, incidence of serious complications, maternal blood factors such as platelet count, and serum levels of liver enzymes such as ALT, AST, bilirubin, and LDH. Discussion: The present trial can importantly contribute to the selection of an appropriate Synbiotic supplement as safe pharmaceutical adjuvants in the treatment of pregnant women with mild preeclampsia and prevention of maternal and neonatal complications. Trial Registration: IRCT20110606006709N20. Registered on August 13, 2022.

Nitroxide—HMP—Protects Human Trophoblast HTR-8/SVneo Cells from H2O2-Induced Oxidative Stress by Reducing the HIF1A Signaling Pathway

Article

Full-text available

Aug 2023

Preeclampsia (PE) is a pregnancy-specific syndrome affecting 5–7% of patients. There is no effective treatment available. Early abnormal placental development is associated with oxidative stress (OS) and a release of reactive oxygen species (ROS) in the placenta. This phenomenon leads to downstream signaling, Hypoxia Inducible Factor 1A (HIF1A) stabilization and transcription of the anti-angiogenic factors soluble fms-like tyrosine kinase 1 (sFLT1) and soluble endoglin (sEng), which are known to cause endothelial and trophoblast dysfunction and cardinal features of PE: hypertension, proteinuria and, in severe cases, eclampsia. We tested whether 3-(Hydroxymethyl)-1-oxy-2,2,5,5-tetramethylpyrrolidine (HMP)—a nitroxide-type antioxidant molecule—can reduce placental OS and mitigate PE symptoms in vitro. We induced OS in human trophoblast (HTR-8/SVneo) cells with hydrogen peroxide (H2O2) and assessed whether modulating cell redox function with HMP reduces cell injury, mitochondrial stress and HIF1A and sFLT1 production. Pre-treatment with HMP reduced mitochondrial-derived ROS production, restored LC3B expression and reduced HIF1A and sFLT1 expression in H2O2-exposed HTR-8/SVneo trophoblast cells. HMP improved the mitochondrial electron chain enzyme activity, indicating that a reduction in OS alleviates mitochondrial stress and also reduces anti-angiogenic responses. In reducing placental trophoblast OS, HMP presents a potential novel therapeutic approach for the treatment of PE. Future investigation is warranted regarding the in vivo use of HMP.

Involvement of oxidative stress in placental dysfunction, the pathophysiology of fetal death and pregnancy disorders

Article

Jun 2023

In brief Placental oxidative stress contributes to both normal and abnormal placentation during pregnancy. This review discusses the potential consequence of oxidative stress-induced placental dysfunction on pregnancies complicated by fetal death and pregnancies with a high risk of fetal death. Abstract The placenta is a source of reactive oxygen free radicals due to the oxidative metabolism required to meet the demands of the growing fetus. The placenta has an array of efficient antioxidant defense systems to deal with rising oxidative stress created by free radicals during pregnancy. Properly controlled physiological (low-level) free radical production is a necessary part of cellular signaling pathways and downstream activities during normal placental development; however, poorly controlled oxidative stress can cause aberrant placentation, immune disturbances and placental dysfunction. Abnormal placental function and immune disturbances are linked to many pregnancy-related disorders, including early and recurrent pregnancy loss, fetal death, spontaneous preterm birth, preeclampsia and fetal growth restriction. This review discusses the role of placental oxidative stress in both normal and pathological settings. Finally, based on previously published work, this review presents multiple lines of evidence for the strong association between oxidative stress and adverse pregnancy outcomes, including fetal death and pregnancies with a high risk of fetal death.

Myc promotes polyploidy in murine trophoblast cells and suppresses senescence

Article

Full-text available

May 2023
DEVELOPMENT

The placenta is essential for reproductive success. The murine placenta includes polyploid giant cells that are crucial for its function. Polyploidy occurs broadly in nature but the regulators and significance in the placenta are unknown. We discovered that many murine placental cell types are polyploid. We identified factors that license polyploidy using single-cell RNA seq. c-Myc is a key regulator of polyploidy and placental development and is required for multiple rounds of DNA replication, likely via endocycles, in trophoblast giant cells. Furthermore, c-MYC supports the expression of DNA replication and nucleotide biosynthesis genes along with ribosomal RNA. Increased DNA damage and senescence occur in trophoblast giant cells without c-Myc, accompanied by senescence in the neighboring maternal decidua. These data reveal c-Myc is essential for polyploidy to support normal placental development, thereby preventing premature senescence. Our study combined with the literature suggests c-Myc is an evolutionarily conserved regulator of polyploidy.

Estimation of Natural Autoantibodies in Preeclampsia by ELI-P Complex

Article

Full-text available

Jan 2023

Preeclampsia (PE) is one of the most serious complications of pregnancy. Disturbances in immune regulation are one of the most common reasons that negatively influences the gestation process and play an important role in pathogenesis of PE We hypothesize that alteration of serum natural autoantibodies' level, may be associated with PE. Natural autoantibodies were measured by ELI-P complex in maternal sera from preeclamptic subjects in comparison to normal pregnancies. The corresponding peaks of immunoreactivity were selectively affected in approximately 89% of preeclampsia and 12 % control pregnant (p<0,001). This study confirms the high level of immunological activation in patients with PE. The presence of autoantibodies implies that autoimmunity might have a causal role in the pathogenesis of PE.

Preeclampsia and Obesity—The Preventive Role of Exercise

Article

Full-text available

Jan 2023
Int J Environ Res Publ Health

Obesity is now recognized as a worldwide epidemic. An inadequate diet and reduced physical activity are acknowledged as the leading causes of excess body weight. Despite growing evidence that obesity is a risk factor for unsuccessful pregnancies, almost half of all women who become pregnant today are overweight or obese. Common complications of pregnancy in this group of women are preeclampsia and gestational hypertension. These conditions are also observed more frequently in women with excessive weight gain during pregnancy. Preeclampsia is one of the most serious pregnancy complications with an unpredictable course, which in its most severe forms, threatens the life and health of the mother and her baby. The early identification of the risk factors for preeclampsia development, including obesity, allows for the implementation of prophylaxis and a reduction in maternal and fetal complications risk. Additionally, preeclampsia and obesity are the recognized risk factors for developing cardiovascular disease in later life, so prophylaxis and treating obesity are paramount for their prevention. Thus, a proper diet and physical activity might play an essential role in the prophylaxis of preeclampsia in this group of women. Limiting weight gain during pregnancy and modifying the metabolic risk factors with regular physical exercise creates favorable metabolic conditions for pregnancy development and benefits the elements of the pathogenetic sequence for preeclampsia development. In addition, it is inexpensive, readily available and, in the absence of contraindications to its performance, safe for the mother and fetus. However, for this form of prevention to be effective, it should be applied early in pregnancy and, for overweight and obese women, proposed as an essential part of planning pregnancy. This paper aims to present the mechanisms of the development of hypertension in pregnancy in obese women and the importance of exercise in its prevention.

Evaluation of maternal serum lipid profiles and clinical chemistry parameters in the prediction of pre-eclampsia in pregnant women attending ANC and delivery services

Preprint

Full-text available

Dec 2022

Pre-eclampsia (PE) is a pregnancy related metabolic syndrome which adversely influence the mother and their newborn infants. Besides, lack of study in our population, some studies also reporting discrepancies in the association of lipid profiles and clinical chemistry parameters with the risk of PE. Hence, this study was designed to evaluate the diagnostic potential of serum lipid profiles and clinical chemistry parameters with PE. Institution-based case-control study was performed at Bahir Dar city governmental hospitals. The study participants were selected through simple random sampling and the socio-demographic data were collected by interview-administered questionnaire. Five ml of venous blood were collected to evaluate lipid profile and clinical chemistry parameters. Descriptive statistics, chi-squared test, multivariable logistic regression and Mann-Whitney U test were utilized for analysis of variables. ROC and combined ROC curve analysis were executed to check the diagnostic accuracy at 95% CI. A total of 336 study participants (168 cases and 168 controls) were included. The median concentrations of serum triglyceride (229 (180-293.75) vs 194 (158.5–255)), total cholesterol (196 (167.25–224) vs 185.5 (158.5-212.75)), ALT (23(20–32) vs 21 (20–25)) and AST (35 (23.25-45) vs 24 (20–35)) values were significantly increased in cases as compared with normal controls. However, the median concentrations of serum total protein (6.7(6.1–7.4) vs 7.1 (6.7–7.6)) and serum calcium (7.6 (7.1–7.9) vs 7.9(7.5–8.3)) were significantly decreased in cases than controls. Positive correlations were observed between blood pressure and serum levels of triglyceride, total cholesterol, ALT & AST values while negative correlations were shown between blood pressure and HDL-cholesterol, total protein and serum calcium values. The combined ROC curve analysis of serum lipid profiles and clinical chemistry parameters showed a moderate prediction potential of PE. Hence, serum lipid profiles and clinical chemistry parameters were utilized as the diagnostic biomarkers of PE. However, to generate tangible evidence on the roles of lipid profiles and clinical chemistry parameters in PE pathogenesis and to include them as routine diagnostic biomarker multi-center prospective studies will be warranted.

Evaluation of Hemodynamics and Oxidative Stress in the Pathophysiology of L-NAME Induced Preeclampsia in Rats

Article

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Dec 2022

To determine the oxidative stress in pre-ecclampsia

Article

Full-text available

Nov 2022

ntroduction: Although preeclampsia was long referred to be "the disease of theories," research in recent years has led to several interesting discoveries that might help us forecast the condition. The maternal endothelium and the placenta both exhibit preeclampsia-related pathology, which may be significantly influenced by oxidative stress. Objective: Thepresent study aims to analyzethe roleof IMA (ischemia-modifiedalbumin),MDA (malondialdehyde), NO (nitric acid), and CRP (C-reactive protein) in patients with pre-eclampsia. Materials and Methods: The study was performed on 84 pregnant females in the third trimester who attended Hi-Tech Medical College & Hospital (Obstetrician & Gynecology Department), Rourkela, Odisha, India. They have divided into two groups A and B.42 pregnant women in Group A were healthy, whereas 42 pregnant women in Group B had preeclampsia. Physical and biochemical parameters were estimated in all the subjects according to standard protocol. Results: When comparing the pre-eclampsia patients with the control group, biochemical markers such as serum NO, IMA, CRP, and MDA exhibited extremely significant p values.Between IMA, MDA, CRP, and NO, there was a strong association. Conclusion: Evaluation of the oxidative stress biomarkers may be very helpful in predicting the condition since oxidative stress is a major factor in the pathogenesis of pre-eclampsia

Maternal serum uric acid, creatinine and blood urea levels in the prediction of pre-eclampsia among pregnant women attending ANC and delivery services at Bahir Dar city public hospitals, northwest Ethiopia: A case-control study

Article

Full-text available

Oct 2022

Background Pre-eclampsia (PE) is a metabolic disorder that adversely affects the lives of mother and their infants. Even though, several studies have been conducted on PE, no effective diagnostic and therapeutic agents were developed so far. Hence, this study was designed to evaluate serum uric acid, blood urea and creatinine levels in the prediction of PE. Methods A hospital-based case-control study was conducted among pregnant women. A simple random sampling technique was applied to select study participants. The socio-demographic and clinical data were collected using an interview-administered questionnaire. Serum samples were used to determine the maternal uric acid, urea and creatinine levels via an automated chemistry analyzer. Independent sample t-test, Pearson correlation test and receiver operating characteristic (ROC) curve analysis were performed to check the association and diagnostic accuracy of variables to PE. Results The mean ages (in years) of the case and control groups were 27.98 ± 5.64 and 27.33 ± 4.45, respectively. The mean serum uric acid and blood urea levels were significantly higher in pre-eclamptic women than in normotensive pregnant women (6.27 ± 0.20 vs 4.43 ± 0.15, and 8.50 ± 3.99 vs 5.67 ± 2.19), respectively but the serum creatinine level is non-significantly increased in cases as compared to controls (0.70 ± 0.05 vs 0.50 ± 0.01). The areas under the ROC curve of serum uric acid, creatinine and blood urea levels were 0.785, 0.735 and 0.764 (sensitivity: 69%, 60.7%, 67.9%; specificity: 73.8%, 75%, 71.4%) with the cutoff points of ≥5.25 mg/dL, ≥0.565 mg/dL and ≥6.5 mg/dL, respectively. Conclusion In this study, we observed a significantly higher concentration of serum uric acid and blood urea values in pre-eclampsia as compared with normotensive pregnant women. Therefore, this suggested that serum uric acid; blood urea and creatinine values can be associated with PE. Moreover, serum uric acid, blood urea and creatinine levels could be carefully utilized as a diagnostic marker for PE, but their inclusion in routine diagnostic test to PE requires large-scale multi-center prospective studies that corroborate our findings.

Role of microRNAs in trophoblast invasion and spiral artery remodeling: Implications for preeclampsia

Article

Full-text available

Oct 2022

It is now well-established that microRNAs (miRNAs) are important regulators of gene expression. The role of miRNAs in placental development and trophoblast function is constantly expanding. Trophoblast invasion and their ability to remodel uterine spiral arteries are essential for proper placental development and successful pregnancy outcome. Many miRNAs are reported to be dysregulated in pregnancy complications, especially preeclampsia and they exert various regulatory effects on trophoblasts. In this review, we provide a brief overview of miRNA biogenesis and their mechanism of action, as well as of trophoblasts differentiation, invasion and spiral artery remodeling. We then discuss the role of miRNAs in trophoblasts invasion and spiral artery remodeling, focusing on miRNAs that have been thoroughly investigated, especially using multiple model systems. We also discuss the potential role of miRNAs in the pathogenesis of preeclampsia.

Efecto de ácido acetilsalicílico sobre la rigidez arterial en el embarazo en una población colombiana: estudio de cohorte prospectivo

Article

Jul 2022

Objetivo: Estimar el efecto del consumo de ácido acetilsalicílico sobre variables hemodinámicas y de rigidez arterial en diferentes momentos de la gestación y sobre el desarrollo de trastornos hipertensivos. Métodos: Estudio de cohorte prospectivo, incluyó 1800 mujeres con gestaciones de 17 semanas o menos, sin antecedente de hipertensión; 487 (27 %) recibieron 100 mg/día de ácido acetilsalicílico antes de la semana 16. Las variables fueron medidas en cuatro momentos de la gestación. El efecto del consumo se estimó usando el modelo de ecuaciones estimables generalizadas, ajustado por variables de confusión. Resultados: Los niveles basales de las variables fueron mayores en el grupo que recibió ácido acetilsalicílico, pero sin diferencia en la tasa de cambio al ser ajustada. Las diferencias ajustadas del índice de aumento aórtico, velocidad de onda de pulso, presión sistólica aórtica central, presión arterial sistólica y presión arterial media, entre pacientes que consumieron ácido acetilsalicílico y quienes no lo consumieron fue 0,5 % (-0,2; 1,3); 0,1 m/s (-0,02; 0,1), 0,9 mm Hg (-0,1; 1,8) 0,7 mm Hg (-0,2; 1,6) y 0,6 mm Hg (-0,2; 1,4), respectivamente. En las pacientes que recibieron ácido acetilsalicílico y desarrollaron preeclampsia, se encontró un aumento promedio ajustado de 0,3 m/s (IC 95 %: 0,1; 0,5) entre cada medición de la velocidad de onda de pulso. Conclusiones: En mujeres que recibieron ácido acetilsalicílico y desarrollaron preeclampsia, se encontró un aumento en el cambio promedio ajustado de la velocidad de onda de pulso, indicando que el consumo del ácido acetilsalicílico no disminuyó la rigidez arterial. Palabras clave: Aspirina, Rigidez vascular, Preeclampsia, Hipertensión inducida en el embarazo

Efecto de ácido acetilsalicílico sobre la rigidez arterial en el embarazo en una población colombiana: estudio de cohorte prospectivo

Article

Jul 2022

Correlation between Neutrophil elastase, Neutrophil and lymphocytes ratio in endothelial dysfunction of preeclampsia

Preprint

Full-text available

Jul 2022

Background: Preeclampsia (PE) is a serious disorder that is unique to pregnancy marked by hypertension, proteinuria, and other systemic disruptions at or after 20th week of pregnancy leading to maternal and neonatal illness and death. Placental hypoxia leads to increased levels of cytokines and inflammatory syncytiotrophoblast microvillous membrane microparticles (STBM) which activates neutrophils leading to in preeclampsia, oxidative stress and endothelial dysfunction are seen. Methods: The present study includes 40 patients hospitalized at the Department of Obstetrics and Gynaecology, HIMSR & HAHC Hospital, Jamia Hamdard, New Delhi. Nitric oxide (NO), Neutrophil elastase (NE), and Neutrophil to Lymphocyte ratio of 20 healthy pregnant women and 20 pregnant women with PE aged 20-45 years were measured. The blood and biochemical parameters in PE patients were analysed. Results: The neutrophil-to-lymphocyte ratio (NLR) was significantly increased in PE patients as compared to the healthy pregnant women. All the biochemical and hemodynamic parameters were assessed. The serum NO concentrations were lower in PE patients as compared to healthy pregnant women. Endothelial dysfunction markers (NE and vWF) were markedly increased in PE patients. The difference was statistically significant with p value <0.05. Conclusion: NLR has been found to be greatly increased in PE patients as compared to control pregnant. Increase in NLR in PE patients occur due to increase in inflammatory markers and endothelial damage. Hence neutrophil to lymphocyte ratio could act as a novel diagnostic biomarker for depicting PE.

Increased carotid artery stiffness after preeclampsia in a cross‐sectional study of postpartum women

Article

Full-text available

Apr 2022

Preeclampsia (PE) is a hypertensive obstetrical complication associated with increased cardiovascular disease risk. Carotid artery functional assessments allow for identification of subclinical vascular dysfunction. This cross-sectional study measured carotid artery functional indices in healthy women with a recent pregnancy complicated by PE, versus women with a prior uncomplicated pregnancy. Women with a history of PE (N = 30) or an uncomplicated pregnancy (N = 30), were recruited between 6 months and 5 years postpartum. Left and right carotid artery ultrasound measured carotid intima media thickness, plaque burden, peak systolic velocity, end diastolic flow velocity and carotid far-wall circumferential strain (FWCS). Carotid FWCS is inversely related to vessel stiffness, where a decrease in FWCS indicates increased vessel stiffness. Right-side FWCS did not differ between women with a history of PE versus normotensive pregnancy. Left carotid artery FWCS was lower in formerly preeclamptic women after adjustment for diameter, pulse pressure, and heart rate compared to women following an uncomplicated pregnancy (3.35 ± 1.08 × 10-3 vs. 4.46 ± 1.40 × 10-3 ; p = 0.003). Those with prior severe PE had the greatest decrease in FWCS adjusted to diameter, pulse pressure, and heart rate compared to healthy controls (p = 0.02). Adjusted FWCS and total serum cholesterol were independent indicators of PE history when present in a logistic regression model with confounding variables including age, body mass index, and resting blood pressure. Further investigation is needed to elucidate if FWCS can be used as a risk stratification tool for future cardiovascular disease following a pregnancy complicated by PE. A history of PE is associated with decreased left FWCS (increased left carotid artery stiffness).

Placental Exosomes Trigger Maternal Inflammation and Vascular Dysfunction in Preeclampsia

Article

Dec 2021

Preeclampsia is a pregnancy-specific disease associated with inadequate placental formation, chronic inflammation, and maternal vascular dysfunction. Preeclampsia affects about 5-8% of pregnant women and it is a prevalent cause of maternal mortality. The level and composition of exosomes in the maternal circulation are altered in preeclampsia, and studies have shown that the major source of this greater level of exosomes is the placenta. We propose that exosomal contents from the placenta trigger maternal inflammation and vascular dysfunction, thereby exacerbating the disease progression. This mini-review will focus on the content of placental exosomes and how they could contribute to the development of preeclampsia.

Acute Atherosis Lesions at the Fetal-Maternal Border: Current Knowledge and Implications for Maternal Cardiovascular Health

Article

Full-text available

Dec 2021

Decidua basalis, the endometrium of pregnancy, is an important interface between maternal and fetal tissues, made up of both maternal and fetal cells. Acute atherosis is a uteroplacental spiral artery lesion. These patchy arterial wall lesions containing foam cells are predominantly found in the decidua basalis, at the tips of the maternal arteries, where they feed into the placental intervillous space. Acute atherosis is prevalent in preeclampsia and other obstetric syndromes such as fetal growth restriction. Causal factors and effects of acute atherosis remain uncertain. This is in part because decidua basalis is challenging to sample systematically and in large amounts following delivery. We summarize our decidua basalis vacuum suction method, which facilitates tissue-based studies of acute atherosis. We also describe our evidence-based research definition of acute atherosis. Here, we comprehensively review the existing literature on acute atherosis, its underlying mechanisms and possible short- and long-term effects. We propose that multiple pathways leading to decidual vascular inflammation may promote acute atherosis formation, with or without poor spiral artery remodeling and/or preeclampsia. These include maternal alloreactivity, ischemia-reperfusion injury, preexisting systemic inflammation, and microbial infection. The concept of acute atherosis as an inflammatory lesion is not novel. The lesions themselves have an inflammatory phenotype and resemble other arterial lesions of more extensively studied etiology. We discuss findings of concurrently dysregulated proteins involved in immune regulation and cardiovascular function in women with acute atherosis. We also propose a novel hypothesis linking cellular fetal microchimerism, which is prevalent in women with preeclampsia, with acute atherosis in pregnancy and future cardiovascular and neurovascular disease. Finally, women with a history of preeclampsia have an increased risk of premature cardiovascular disease. We review whether presence of acute atherosis may identify women at especially high risk for premature cardiovascular disease.

Assessing Oxidative Stress by Thiol/Disulfide Homeostasis Among Vitamin D-Deficient Patients

Article

Full-text available

Dec 2021

Objective: Thiol/disulfide (T/DS) homeostasis represents a promising new approach to evaluate oxidative stress. Therefore, we aimed to examine T/DS homeostasis in vitamin D (VitD)-deficient patients. Methods: We enrolled 154 patients with VitD deficiency and 154 healthy control subjects in the study. For both groups, native thiol, total thiol, and disulfide values were measured. Additionally, considering the obtained 25-hydroxycholecalciferol [25(OH)D] levels, the patient group was further divided into two subgroups (Group 1: <10 ng/mL, Group 2: 10-20 ng/mL), which were compared in more depth according to the specified parameters. Results: Values of native thiol, total thiol, and disulfide measured in the combination of Groups 1 and 2, comprising individuals with VitD deficiency, proved to be higher in comparison to the control group with statistical significance (p=0.007, p=0.028, and p<0.001, respectively). When subgroups were considered according to VitD classifications, native thiol and total thiol were again higher in Group 1 in comparison to the values obtained for control subjects (p=0.022; p<0.001). While the total thiol level of Group 2 was higher than that of controls (p<0.001), no difference with statistical significance was obtained in the comparison of disulfide levels among the indviduals of Group 1, Group 2, and the controls (p=0.081). Conclusion: In this study, among patients with VitD deficiency, we have confirmed that values of native thiol and total thiol were increased, while the T/DS balance was found to have shifted in favor of the thiol level.

Plasma adenosine deaminase activity and antioxidant status in preeclampsia compared to healthy pregnant and non-pregnant women.

Article

Sep 2021

Oxidative stress-induced senescence in mature, post-mature and pathological placentas

Article

Sep 2021
PLACENTA

Placental Oxidative Stress in the pathogenesis of Hypertensive Disorders of Pregnancy

Article

Full-text available

Jun 2021

Background: Hypertensive disorders of pregnancy are a major complication of pregnancies and can lead to fetal growth retardation, premature delivery and maternal morbidity and mortality. The study aimed at assessing the potential role of the placenta in the pathogenesis of hypertensive disorders of pregnancy. Methods: This study was a case-control study conducted at the Upper East Regional Hospital, Ghana from September, 2016 to March 2017. Twenty (20) pregnant women with hypertensive disorders of pregnancy (i.e., Pregnancy induced hypertension, preeclampsia and eclampsia) as cases and 30 normotensive pregnancies as controls, were included in the study. The placenta was excised after delivery, homogenized and assayed for malondialdehyde, catalase, total peroxide, oxidative stress index, total antioxidant capacity and placental lipid profile. Results: The ages of the two groups were similar, with malondialdehyde (p = 0.001) and Oxidative Stress Index (p < 0.001) being significantly higher in the hypertensive group compared to the control group whereas Total Antioxidant Capacity (p < 0.001) and Catalase (p = 0.011) were significantly higher in the control group compared to the hypertensive group. The proportion of normal, term and livebirth deliveries were significantly higher among controls compared to the hypertensive disorders of pregnancy group. Among the estimated oxidative stress markers, total antioxidant capacity turned out to be the best predictor of the hypertensive disorders of pregnancy. Conclusion: Our findings suggest oxidative stress in women with hypertensive disorders of pregnancy and that placental oxidative stress could be the driving factor for the pathogenesis and severity of these hypertensive disorders of pregnancy.

Study of uterine artery perfusion and total antioxidant capacity in second trimester pregnancy

Article

Jul 2021

A Case-Control Study of Relevance Between NOS2 rs2297518 Polymorphism with Preeclampsia Risk in the Chinese Han women

Preprint

Full-text available

May 2021

Backgroud: Inducible Nitric Oxide Synthase (iNOS) acts on the contraction and expansion of blood vessels by mediating the synthesis of Nitric Oxide (NO), which is implicated in the pathophysiology of preeclampsia (PE) associated with systemic vasoconstriction. The polymorphism of NOS2, the gene of coding iNOS, can affect the function of protein. Therefore, we aimed to explore whether the polymorphism site rs2297518 in NOS2 is associated with susceptibility of PE in a Chinese Han population. Methods and Results:Genotyping the NOS2 rs2297518 polymorphism through TaqMan real-time fluorescence quantitative polymerase chain reaction (PCR) after DNA extraction from blood samples in this case-control study including 979 PE patients and 1187 healthy pregnant women. Using independent sample t-test and chi-square test to analyse clinical data and experimental results. We performed the odds ratios (ORs) and 95% confidence intervals (CIs) to estimate the degree of the association.There was no statistical significance in the genetic distributions for the polymorphism of rs2297518 between the PE and control groups (c²=1.43, p=0.49 by genotype frequency, c²=0.85, p=0.36, odds ratio=1.07, 95% confidence interval 0.92-1.25 by allele frequency), and no differences among early/late-onset or mild/severe PE and controls was seen. Conclusion: Our results indicated that the NOS2 rs2297518 polymorphism may be not play a major role in the susceptibility to PE in the Chinese Han population. Therefore, it is essential to test other polymorphisms of this gene to validate a potential relationship for susceptibility to PE.

INDUCED OXIDATIVE STRESS BY DEFEROXAMINE (DESFERAL) DURING THE PREGNANCY: PRE AND POST-NATAL DEVELOPMENTAL STUDY

Article

Full-text available

Feb 2021

The aim of the study is to evaluate the effect of induced oxidative stress by the deferoxamine (desferal) during the pregnancy on pre and post-natal developmen. One hundred twenty adult female albino rats, 3 months old, with an average weight of 175-200 g, were randomly distributed into two main groups (60 rats/group). The 1st (control group) was injected with 0.3 ml physiological salt solution / animal, and the 2nd group was injected with 100 mg deferral/kg B.W. which was given intraperitoneal once daily for three consecutive weeks (during the pregnancy period). At the end of the treatment, each group in turn was divided into two parts, each section comprising 10 animals, blood samples were collected for biochemical analysis, then uterine and fetal tissues collected to observation the studied parameters. Results showed decrease in the numbers of implantation and blastocysts. The number of alive embryos were significantly reduced with an increasing number of dead and reabsorbed embryos, malformation of fetus increase in uterine of the stressed female group compared with control group. Postnatal observations showed significant variations in postnatal development parameters. Our study suggests that the deferral injection has a pro-oxidant capacity on rats' model at dose of 100 mg/kg, and the oxidative stress plays an important role during pregnancy especially on prenatal development as well as persist up to postnatal life.

Quercetin stimulates trophoblast fusion via the mitochondrial function

Article

Full-text available

Jan 2024

The fusion of mononuclear trophoblasts into multinucleate syncytiotrophoblasts is the critical event in the process of syncytialization, and its dysregulation can lead to pregnancy complications, notably hypertensive disorders of pregnancy (HDP). Oxidative stress may disrupt trophoblast syncytialization in HDP. Specifically, placentas with HDP exhibit impaired mitochondria, giving rise to the generation of reactive oxygen species (ROS) and subsequent oxidative stress. Quercetin, a bioflavonoid known for its antioxidant and anti-aging properties, has the potential to mitigate oxidative stress during trophoblast syncytialization. However, the precise mechanism underlying the action of quercetin in these processes remains to be elucidated. To explore the impact of quercetin on syncytialization, mitochondrial function, and ROS generation, cyclic AMP-stimulated BeWo cells were treated with quercetin. The expression of markers associated with cell fusion, mitochondrial function, and oxidative stress was determined using qPCR and western blotting. Additionally, morphological syncytialization and mitophagy (mitochondrial degradation) were assessed by immunofluorescence analysis. Our results revealed that quercetin increased the expression of syncytialization markers and promoted cell fusion. Furthermore, this compound also upregulated markers associated with mitophagy and mitochondrial fusion, which are corroborated by visual evidence of mitophagy through the fluorescence microscope. Cell fusion naturally stimulated ROS generation, which was attenuated by quercetin. Quercetin downregulated the expression of NRF2 and HO-1 during syncytialization, while increasing the expression of sirtuin1/3/6, which are known to play essential roles in antioxidant responses. In conclusion, quercetin effectively regulates mitochondrial function through its antioxidant properties and the suppression of ROS generation, ultimately promoting trophoblast fusion, suggesting that the flavonoid has the potential to ameliorate pregnancy-related disorder stemming from placental dysplasia.

Oxidative Stress in Pregnancy

Article

Full-text available

Dec 2023

Recent years have seen an increased interest in the role of oxidative stress (OS) in pregnancy. Pregnancy inherently heightens susceptibility to OS, a condition fueled by a systemic inflammatory response that culminates in an elevated presence of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in the circulatory system. The amplified OS in pregnancy can trigger a series of detrimental outcomes such as underdevelopment, abnormal placental function, and a host of pregnancy complications, including pre-eclampsia, embryonic resorption, recurrent pregnancy loss, fetal developmental anomalies, intrauterine growth restriction, and, in extreme instances, fetal death. The body’s response to mitigate the uncontrolled increase in RNS/ROS levels requires trace elements that take part in non-enzymatic and enzymatic defense processes, namely, copper (Cu), zinc (Zn), manganese (Mn), and selenium (Se). Determination of ROS concentrations poses a challenge due to their short half-lives, prompting the use of marker proteins, including malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT), and glutathione (GSH). These markers, indicative of oxidative stress intensity, can offer indirect assessments of pregnancy complications. Given the limitations of conducting experimental studies on pregnant women, animal models serve as valuable substitutes for in-depth research. This review of such models delves into the mechanism of OS in pregnancy and underscores the pivotal role of OS markers in their evaluation.

Low indoleamine 2, 3 dioxygenase (IDO) activity is associated with psycho-obstetric risk

Article

Dec 2023

Mariem Dissertation-Ch-D06122023- LPS and preeclampsia Rat Model

Thesis

Nov 2023

7. Summary This study investigated the effects of chitosan on pregnancy in rats. The injection of LPS into pregnant rats at GD5 resulted in a PE rat model with the main characteristics of PE. Pregnancy complications, such as PE, are a significant cause of morbidity and mortality worldwide. It has been linked to preterm labor, IUGR, IUFD, and embryonic resorption. The exact origin of PE remains unknown, but evidence suggests an aberrant maternal-fetal inflammatory response causing insufficient SA remodeling. Post-conception, the maternal CVS experiences changes, leading to increased UBF. Restricted UBF affects both the mother and fetus during pregnancy, increasing susceptibility to metabolic diseases like diabetes and CVS diseases later in life. This study aimed to evaluate changes in UBF during pregnancy in rats using NICD, study the effects of chitosan in ameliorating LPS effects during early pregnancy, study the effects of chitosan and LPS on the translation of water transporters and angiogenic proteins during pregnancy in preeclamptic rats, and study the ability of chitosan to improve conceptus and fetal parameters intrauterine via enhancing placental functions. The study involved 50 mature female Wistar albino rats aged 8–10 weeks, weighing 130–190 g. A vaginal smear was obtained from the females to determine those in estrus. The rats were caged with male rats for 48 hours, and they were examined for the presence of vaginal plugs every morning (GD1). Starting on GD3, rats were exposed to doppler imaging of the UTA to evaluate changes in UBF noninvasively, and the SBP was measured using tail-cuff plethysmography (BP-98A) every three days during the whole gestational length. The fifty female rats were assigned randomly into five experimental groups (control, Chitosan, LPS, LPS+Ch, and Ch+LPS+Ch) of ten rats each, each receiving doses of different treatments daily from GD5 until GD18. The placentae, ovaries, uteri, fetal liver, fetus, amniotic fluid, urine, and serum were collected for further histopathological, endocrinological, biochemical, and gene expression analysis. Placentas were collected, dissected longitudinally through the center, and half of the obtained placentas were washed in normal saline and fixed. Small pieces of ovaries and placental tissue were also fixed and examined under both light and electron microscopes. RNA extraction from the placental tissue and amniotic fluid was performed using Triazole reagent, and gene expression analysis was conducted against B-actin as a housekeeping gene. The normality of quantitative data was determined using normal probability plots and the Kolmogorov-Smirnov test. The levels of protein in urine increased, and the SBP and DBP increased in the LPS-treated group. The infusion of LPS at GD5 resulted in a significant decrease in the fetal number and the weight of the placentae. Chitosan showed the capability to ameliorate the effects of LPS, either after LPS administration or pre- and post-LPS infusion, that the UBF parameters changed significantly with the progress of gestation until the sacrification day. The LPS-treated group showed decreased GSH levels and increased levels of MDA, NO, and TAC in the placental tissue, the uterine tissue, and the fetal hepatic tissue, while the chitosan-treated groups showed increased GSH levels and decreased levels of MDA, NO, and TAC. Chitosan-treated groups showed increased levels of expression of AQP 3, AQP 4, VEGF, and PGF and decreased levels of expression of CAS3, BAX, and TNF-α1 in both placental tissue and amniotic fluid, considering the AQP 3, AQP 4, VEGF, and PGF decreased expression levels and the CAS3, BAX, and TNF-α1 increased expression levels in the LPS-treated group. In summary, Chitosan demonstrated the ability to diminish the effects of LPS both before and after LPS infusion, as well as after LPS injection. The supplementation of chitosan resulted in an improvement in the general health and well-being of the pregnant rats. These results imply that chitosan might be a useful intervention for controlling IUGR, PE, placental functioning, and enhancing the quality of pregnancies.

Relationship between level of vitamins and Hydatiform Mole in Women: A Systematic Review Study

Article

Full-text available

Jul 2020

Introduction: Hydatidiform mole is one of the emergency risks in pregnancy that can threaten the life of women of childbearing age with risk of death. Various studies have reported different risk factors for this disease. One of these factors is nutritional deficiency, especially vitamin deficiencies, which can lead to this condition. Therefore, this study was performed with aim to systematic review of the relationship between the blood level of vitamins in women and hydatidiform mole. Methods: In this systematic review study, for finding the related articles, the international databases such as: Web of Science, Scopus, PubMed and Embase, Google Scholar and national databases such as: MagIran, SID, IranDoc and IranMedex were evaluated using the keywords of: "Hydatidiform Mole", "Gestational Trophoblastic Disease", "Molar Pregnancy" and "Vitamin" which were combined with the OR and AND Boolean operators without time limitation. Finally, two researchers independently reviewed the articles for assessment of the quality (by using NOS checklist) and data extraction. Results: Finally, 10 articles were included with total sample size of 1134 women. The publication¢s year of papers was from 1988 to 2018 and all studies were case-control. The findings showed that level of vitamins A, D, E, C, B9 and B12 are associated with hydatidiform mole, so that decreasing of these vitamins leads to molar pregnancy. In most of the studies, there was decreased level of these vitamins in both complete and incomplete molar pregnancy. Conclusion: Decreased level of vitamins A, D, E, C, B9 and B12 can increase the risk of molar pregnancy. Therefore, by examining and determining the nutritional deficiencies in women with history of molar pregnancy, we can evaluate the effect and administration of vitamin supplements on recurrence of hydatidiform mole can by designing clinical trials.

The Effect of Liprotide-Encapsulated Vitamin D3 on MDA and SOD in Rats Deficient Vitamin D and Calcium

Article

Full-text available

Feb 2023

Background: Vitamin D deficiency is frequently correlated with elevated malondialdehyde (MDA) levels and decreased superoxide dismutase (SOD) activity. Several studies have demonstrated that vitamin D3 can reverse intracellular oxidative stress. However, vitamin D is prone to deterioration and instability. Liprotides contain lipids and proteins that can prevent vitamin D from oxidating.Objective: This study aims to investigate the effects of liprotide-encapsulated vitamin D3 on MDA concentrations and SOD activity in calcium and vitamin D-deficient rat models.Methods: The experimental post-test-only control group study used 24 Wistar rats randomly in 4 groups. Groups K(-), K(+), and P were fed a vitamin D and calcium-depleted AIN-93M diet for 14 days. Standard feed AIN-93M was received by normal groups (KN). Groups K- were deficient rats in vitamin D and calcium without intervention. The groups of K+ and P were given vitamin D3 (180 IU) which was non-encapsulated and liprotide-encapsulated for 28 days.The SOD activity was quantified with Superoxide Dismutase (SOD) Activity Assay Kit, while MDA levels were determined using Thiobarbituric Acid Reactive Substance (TBARS) method. The statistical analysis used One-way ANOVA test with Least Significant Difference follow-up test.Results: The MDA levels and SOD activity in the K+ and P groups had significant differences (p<0.05) against the control group. Liprotides-encapsulated vitamin D3 significantly reduced MDA levels and enhanced SOD activity compared to non-encapsulated in rats with a deficiency in vitamin D and calcium.Conclusion: Liprotide-encapsulated vitamin D3 has the potential to increase SOD activity and decrease MDA levels.

Inhibition of Angiotensin II Type 1 Receptor Agonistic Autoantibodies by Direct Binding Does Not Impact RUPP Offspring Birth Weight and Blood Pressure at Adulthood

Article

Mar 2023

Background: Preeclampsia (PE), new onset hypertension with end-organ damage in pregnancy, is associated with maternal death and morbidity, low birth weight, and B cells producing agonistic autoantibodies to the angiotensin II type 1 receptor (AT1-AA). AT1-AA is produced during pregnancy, postpartum, and is in the fetal circulation of PE women. AT1-AA is shown to contribute to endothelial dysfunction, renal dysfunction, hypertension, fetal growth restriction, and chronic inflammation in PE women. The Reduced Uterine Perfusion Pressure (RUPP) rat model of PE exhibits these features and we have shown that administration of a seven amino acid sequence peptide ('n7AAc'), which blocks the actions of the AT1-AA, improves PE features in the RUPP rat. However, 'n7AAc's effect on the long-term health of RUPP rat offspring is unknown. Objectives: The objective of this study is to test the hypothesis that inhibition of AT1-AA during pregnancy will improve offspring birth weight and prevent increased cardiovascular risk in offspring at adulthood. Study design: To test our hypothesis, 'n7AAc' (24 ug/day) or vehicle (saline) was given on gestation day 14 via mini-osmotic pumps to sham-operated (Sham) and RUPP Sprague Dawley rat dams. Dams were allowed to deliver naturally and pup weights were recorded within 12 hours of birth. Pups were aged to 16 weeks at which time mean arterial pressure (MAP) was measured and whole blood was collected to measure immune cells by flow cytometry, cytokines by ELISA, and AT1-AA by bioassay. A two-way ANOVA with Bonferroni's multiple comparison post hoc test was used for statistical analysis. Results: There was no significant change in offspring birth weight of 'n7AAc' treated RUPP males (5.63±0.09 g) or females (5.66±0.14 g) compared to vehicle RUPP males (5.51±0.17 g) or females (5.74±0.13 g). Additionally, 'n7AAc' did not affect the birth weight of sham males (5.83±0.11 g) or females (5.64±0.12) compared to vehicle sham males (5.811±0.15 g) or females (5.40±0.24 g). At adulthood, mean arterial pressure was unchanged in 'n7AAc' RUPP males (133±2 mmHg) and females (127±3 mmHg) compared to vehicle RUPP males (142±3 mmHg) and females (133±5 mmHg), 'n7AAc' sham males (133±3 mmHg) and females (135±3 mmHg), as well as vehicle sham males (138±4 mmHg) and females (130±5 mmHg). Circulating AT1-AA was increased in vehicle RUPP males (10±2 ΔBPM) and females (14±2 ΔBPM) and 'n7AAc' RUPP males (11±2 ΔBPM) and females (11±2 ΔBPM) compared to vehicle sham males (1±1 ΔBPM) females (-1±1 ΔBPM) and 'n7AAc' sham males (-2±2 ΔBPM) and females (-2±2 ΔBPM). Conclusions: Our findings indicate that perinatal 'n7AAc' does not negatively impact offspring survival or weight at birth. Perinatal 'n7AAc' did not prevent increased cardiovascular risk in offspring but it did not cause increased risk compared to controls. Furthermore, perinatal 'n7AAc' does not affect endogenous immunological programming as observed by no change in circulating AT1-AA in either sex of adult RUPP offspring.

Evaluation of serum melatonin levels in preeclampsia - a case control study

Article

Full-text available

Feb 2022

Aim: This study aimed to evaluate the association of serum melatonin levels in term pre-eclampsia (PE) subjects and compare it with normotensive healthy term pregnant women. Methodology: The study was conducted between November 2018 and April 2020. As per sample size calculation, 50 cases and 50 controls were enrolled in the study, matched for age, race and gestational age. Ethical clearance was obtained from Institutional Ethical Committee for human research. Night time (2 am) samples were taken. Analysis was done by ELISA test. Day time samples were also taken in cases to compare day and night time serum melatonin levels. Results: Mean value of serum melatonin level was lower in patients with preeclampsia (93.18±61.5pg/mL) in Indian population as compared to controls (109.18±69.86pg/mL), though not statistically significant (p=0.446). On plotting ROC curve for predicting severe PE we found that melatonin level with cut off of 96.9pg/mL had AUC of 0.88 and was statistically significant. Severe PE (47.32±26.88pg/mL) had significantly (p=0.001) lower serum melatonin level when compared to non-severe PE (123.76±59.16pg/mL). Significantly lower value of melatonin was observed (p

Stress-Sensitive Regulators of Fetal Neurodevelopment in HIV and Preeclampsia: An Immunocytochemical Appraisal of Placental OGT and T4 Levels

Article

Dec 2023

Preeclampsia and HIV are a significant burden to maternal health globally, especially in low-middle income countries such as South Africa. In the KwaZulu-Natal province, SA antenatal HIV prevalence is 41.1%, while PE is 12%. PE and HIV infections are maternal stress and inflammation that impact placental function and fetal development. Therefore, this study investigated the impact of the comorbidity of PE and HIV on placental stress and neurodevelopment. Placentae were obtained from four cohorts of pregnant women: normotensive HIV negative, normotensive HIV positive, preeclamptic HIV negative, and preeclamptic HIV positive. The placental tissue sections were immunostained for OGT and T4. Our findings showed that the maternal weight, diastolic, and systolic blood pressures (BP) were higher in PE vs. the normotensive groups, irrespective of HIV status. In addition, significant changes were noticed in the placental weight, fetoplacental ratio, and placental efficiency coefficient. Our findings showed that the maternal weight, diastolic, and systolic blood pressures (BP) were statistically higher in the PE compared to the normotensive. No significant differences were observed between HIV positive and HIV negative groups. In addition, significant changes were noticed in the placental weight, fetoplacental ratio, and placental coefficient. Furthermore, considerable upregulation in the placental expression of OGT in both the conducting and exchange villi of PE and concomitant downregulation in HIV-positive patients compared with Normotensive and HIV-negative individuals, respectively. Our results provide inferential evidence on the dysregulation of OGT in the comorbidity of PE and HIV. This may mediate a compromised programmed outcome of an adverse maternal environment during pregnancy and consequently affect fetal development.

Thrombocytopenia in pregnancy

Chapter

Apr 2006

There are many haematological complications associated with obstetrics, pregnancy and gynaecology, and unfortunately, they often lead to significant morbidity or mortality for both mother and child. As the first comprehensive reference on all aspects of haematological complications of obstetrics, pregnancy and gynaecology this book will be a valuable resource to haematologists, obstetricians, gynaecologists, reproductive medicine specialists, internists, anaesthesiologists and others. The chapters are written by acknowledged experts in the field, and for each condition covered the etiology, pathophysiology, clinical and laboratory diagnosis and management are discussed where appropriate.

Placenta – clinical scenarios

Chapter

Jan 2009

Impact of oxidative stress in response to malarial infection during pregnancy: Complications, histological changes, and pregnancy outcomes

Article

Jun 2022

Background and objectives: Pregnancy malaria is a major underestimated global public health problem. To understand the involvement of oxidative stress (OS) in the pathophysiology of placental malaria, OS biomarkers, malondialdehyde (MDA), uric acid (UA), and superoxide dismutase (SOD) levels were analyzed and correlated to placental histopathological changes and pregnancy outcomes. Methods: A hospital-based study was conducted in Mangaluru, Karnataka, India, to analyze the changes in hematological parameters and the serum OS biomarker levels. Histological analysis of placenta, associated complications, and pregnancy outcomes were compared using Kruskal-Wallis test, and pairwise comparison between two groups was made by Mann-Whitney U-test. Correlations were calculated by Pearson's and Spearman's rank correlations. Results: Among 105 pregnant women, 34 were healthy controls and the infected group comprised of Plasmodium Vivax (Pv) (n = 48), Plasmodium falciparum (Pf) (n = 13), and mixed (n = 10) malaria infections. Of 71 infected cases, 67.6% had mild malaria, whereas 32.4% had severe malaria. The white blood cell and C-reactive protein levels were found to increase, whereas hemoglobin, red blood cell, and platelet levels decreased during both types of malarial infections. The MDA and UA values increased and SOD levels decreased particularly during severe Pf infections. Histological changes such as syncytial knots, syncytial ruptures, and fibrinoid necrosis were observed particularly during Pf infections and leukocyte infiltration was observed in Pv malaria. Conclusion: Evaluation of MDA, UA, and SOD levels can serve as an indicator of OS during pregnancy malaria. The OS during pregnancy may lead to complications such as severe anemia, pulmonary edema, intra uterine growth retardation, premature delivery, and low birth weight, not only during Pf but also in Pv malaria. It is important to create awareness among rural and immigrant population residing in Mangaluru and its surroundings about required preventive measures and free government-supported antenatal care services.

Gadd45 in Preeclampsia

Chapter

May 2022
ADV EXP MED BIOL

Preeclampsia is a pregnancy-induced complex of multiple pathological changes. Numerous stresses during pregnancy, including hypoxia, immune activation, inflammatory cytokines, and oxidative stress were reported as contributing factors to the preeclamptic pathology. Seeking common sensors of various stressors in preeclampsia is of new interest and can potentially benefit in disease prevention and treatment. Recent studies have highlighted the role of the Gadd45a protein as a stress sensor in preeclampsia. In response to various pathophysiological stressors, notably hypoxia, oxidative stress, inflammatory cytokines, and AT1-AAs, Gadd45a activates Mkk3-p38 and or JNK signaling. This, in turn, results in immunological and inflammatory changes as well as triggering the production of circulating factors such as sFlt-1, which are believed to account for many of the pathophysiological-related symptoms of preeclampsia. Activation of inflammatory/immune responses in preeclampsia may function in a feedback loop to maintain elevated expression of Gadd45a protein.

Lipid Profile Changes in Pregnant Women with Pre-Eclampsia and Their Correlation with Severety of Pre-Eclampsia

Article

Sep 2020

Objectives: To find out whether there is a lipid profile changes in pregnant women with preeclampsia and if we can use these lipid profile changes as markers of the severity of preeclampsia (for follow up to avoid leaving the patient reaching ecplamptic stage). Design: A prospective case-control study. Setting: AL- Kadhimiya Teaching hospital/department of Obstetrics and Gynecology. Materials and Methods: The study included 120 pregnant women in the third trimester. They were divided into three groups. The study group consists of 60 preeclamptic and eclamptic women, 25 women had mild pre-eclampsia and 35 women with severe preeclampsia. The control group consists of 60 normotensive pregnant women. Blood sample was drown after 8-10 hours fasting. Triglyceride, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and very low-density lipoprotein cholesterol levels were measured. Results: Triglyceride and VLDL-C level of severe Preeclampsia group and mild Preeclampsia group was higher than the control group, but the difference between the severe PE group and the control group was statistically significant (p<0.05). Serum cholesterol in the severe PE group was significantly higher than in mild PE group and in the control group (p<0.05). LDL-C and HDL-C levels were determined similarly in all groups (p>0.05). A highly significant positive correlation between the level of proteinuria and serum cholesterol levels, LDL-C, TG and VLDL-C levels. While there was significantly negative correlation between proteinuria and HDL-C levels. Also, a significant positive correlation between the systolic-tension and serum cholesterol levels, TG, VLDL-C levels and among the diastolic-tension and with LDL-C, TG, VLDL-C levels. Conclusion: Changes in levels of lipid profile are related with preeclampsia, especially with severe preeclampsia.

Angiogenesis and Preeclampsia

Chapter

Jan 2022

The developing human placenta undergoes extensive angiogenesis (neovascularization from preexisting blood vessels) and vasculogenesis (blood vessel generation from angioblast precursor cells), along with a process of vascular mimicry (pseudo-vasculogenesis) as cytotrophoblasts convert from an epithelial to an endothelial phenotype. Failure of these changes has been linked to the pathogenesis of preeclampsia. Placentas in preeclamptic subjects produce an excess of antiangiogenic factors that enter the maternal circulation and impair vascular endothelial cell signaling of proangiogenic factors. In this chapter we discuss evidence that measurement of circulating angiogenic factors in the plasma accurately reflects the morbidity of severe disease and the risk of adverse outcomes related to preeclampsia. The mechanisms as to how antiangiogenic proteins cause preeclamptic and eclamptic signs and symptoms are reviewed, as are their implications for prevention or cure.

Coenzyme A restriction as a factor underlying pre-eclampsia and other antenatal conditions.

Preprint

Full-text available

Dec 2021

Pre-eclampsia is the most common pregnancy complication affecting 1 in 20 pregnancies, characterized by high blood pressure and signs of organ damage, most often to the liver and kidneys. Metabolic network analysis of published lipidomic data points to a shortage of Coenzyme A (CoA). Gene-expression profile data reveal alterations to many areas of metabolism and, crucially, to conflicting cellular regulatory mechanisms arising from the overproduction of signalling lipids driven by CoA limitation. Adverse feedback loops appear, forming sphingosine-1-phosphate (a cause of hypertension, hypoxia and inflammation), cytotoxic isoketovaleric acid (inducing acidosis and organ damage) and a thrombogenic lysophosphatidyl serine. These also induce mitochondrial and oxidative stress, leading to untimely apoptosis, which is possibly the cause of CoA restriction. This work provides a molecular basis for the signs of pre-eclampsia, why other conditions are risk factors and what might be done to treat and reduce the risk of this and related diseases.

The Antioxidant System Activity during Normal Pregnancy and Pregnancy Followed by Hypoxic Stress

Article

Jul 2021

The Predictive Value of First-trimester Thiol/Disulfide Homeostasis in Preeclampsia

Article

Full-text available

Apr 2021
JCPSP-J COLL PHYSICI

Objective: To investigate the efficacy of first-trimester thiol/disulfide homeostasis (t/dh), a new oxidative stress marker, in predicting preeclampsia. Study design: Prospective cohort study. Place and duration of study: Department of Obstetrics and Gynecology, University of Health Sciences, Zeynep Kamil Women and Children Diseases Training and Research Hospital, Istanbul, Turkey, Department of Obstetrics and Gynecology, Bursa Yüksek Ihtisas Training and Research Hospital, Bursa, Turkey, from March 2016 to February 2019. Methodology: In this multi-centre,serum samples of women with839 singleton pregnancies were collected between 11+0 to 13+6gestational weeks. A total of 215 singleton pregnant women were included in the study. The patient group consisted of 38 women, who were diagnosed with preeclampsia; while the control group consisted of 177 healthy pregnant women without any complication during pregnancy and after delivery. Totalthiol (TT) was estimated by the sum of existing thiol groups and reduced thiol groups (S-S and -SH). After the native thiols (-SH) and (TT) were determined, the disulfide (-SS) amounts, disulfide/total thiol percent ratios (-SS/-SH + -SS), disulfide/native thiol percent ratios (-SS/-SH), and native thiol/total thiol percent ratios (-SH/-SH + -SS) were calculated. Results: There were no statistically significant differences between the groups in terms of[(-SH), (TT), (-SS), (-SS/-SH), (-SS/-SH + -SS), and (-SH/-SH + -SS)] six t/dh variables(p>0.05).The first-trimester body mass index (BMI) was statistically different between the two groups (p<0.001). In the receiver operating characteristic curve analysis, none of the concentrations of thiol levels and ratios was found to have a significant predictive value for preeclampsia. The BMI was a significant predictor for preeclampsia (area under curve: 0.749, p<0.001). Conclusion: Maternal serum t/dh at 11+0 to 13+6 weeks of gestation does not predict preeclampsia and t/dh may be the consequence rather than a cause in the pathogenesis of preeclampsia. Key Words: First-trimester, Preeclampsia, Sulfhydrylcompounds, Thiols.

Role of nitric oxide in obstetrics

Article

Full-text available

Jan 1996

Patients with preeclampsia develop agonistic autoantibodies against the angiotensin AT1 receptor

Article

Full-text available

May 1999

Immune mechanisms and the renin–angiotensin system are implicated in preeclampsia. We investigated 25 preeclamptic patients and compared them with 12 normotensive pregnant women and 10 pregnant patients with essential hypertension. Antibodies were detected by the chronotropic responses to AT1 receptor–mediated stimulation of cultured neonatal rat cardiomyocytes coupled with receptor-specific antagonists. Immunoglobulin from all preeclamptic patients stimulated the AT1 receptor, whereas immunoglobulin from controls had no effect. The increased autoimmune activity decreased after delivery. Affinity-column purification and anti–human IgG and IgM antibody exposure implicated an IgG antibody directed at the AT1 receptor. Peptides corresponding to sites on the AT1 receptor's second extracellular loop abolished the stimulatory effect. Western blotting with purified patient IgG and a commercially obtained AT1 receptor antibody produced bands of identical molecular weight. Furthermore, confocal microscopy of vascular smooth muscle cells showed colocalization of purified patient IgG and AT1 receptor antibody. The protein kinase C (PKC) inhibitor calphostin C prevented the stimulatory effect. Our results suggest that preeclamptic patients develop stimulatory autoantibodies against the second extracellular AT1 receptor loop. The effect appears to be PKC-mediated. These novel autoantibodies may participate in the angiotensin II–induced vascular lesions in these patients.

Brosens, I. A. Morphological changes in the utero-placental bed in pregnancy hypertension. Clin. Obstet. Gynaecol. 4, 573-593

Article

Full-text available

Jan 1978
Clin Obstet Gynaecol

Ivo A Brosens

Reactive oxygen metabolites cause massive, reversible proteinuria and glomerular sieving defect without apparent ultrastructural abnormality

Article

Full-text available

Nov 1991

To identify the specific in vivo renal effect of reactive oxygen species (ROS), hydrogen peroxide (H2O2) was infused directly into the left renal artery in Munich-Wistar rats. H2O2 (5 to 50 mumol over 1 h) induced a dose-dependent increase in urine protein excretion rate in infused kidneys, reaching a maximum at the dose of 35 mumol (on average, a 60-fold increase from baseline). The H2O2 (35 mumol)-induced proteinuria peaked over 1 h and completely normalized by 24 h after the infusion. Electrophoresis revealed that the urine protein is primarily of glomerular origin. Fractional clearances of graded-size neutral dextran of larger molecular radii, an index of glomerular size selectivity, were significantly and substantially elevated immediately but normalized by 24 h after the infusion. GFR and RPF rate remained unchanged throughout the entire time course examined. The H2O2-induced proteinuria was largely prevented by pretreatment with catalase (20 mg, iv) or deferoxamine (30 mg/100 g body wt, iv). Thus, iron-dependent metabolites of hydrogen peroxide appear to be involved in this proteinuria and glomerular size-selective defect. Light and electron microscopy, including determination of anionic site density at lamina rara externa of glomerular capillary wall by polyethyleneimine staining, did not reveal any appreciable abnormality throughout the study period, including at the peak of proteinuria. Thus, ROS can cause massive, reversible proteinuria by inducing a molecular size-selectivity defect of the glomerular capillary wall without apparent ultrastructural abnormalities. The results raise the possibilities: (1) that persistent proteinuria of a variety of renal diseases may reflect persistence of pathogenic ROS acting on glomeruli because the potent proteinuric effect of ROS can be transient (2) that the light and electron microscopy abnormalities in glomeruli of ROS-induced renal injuries reported thus far may have no direct causal linkage to proteinuria; and, finally, (3) ROS-induced reversible proteinuria may relate to the mechanism of clinical functional proteinuria, which involves increased oxygen and ROS metabolism, e.g., exercise-induced proteinuria.

Morphological Changes in the Utero-Placental Bed in Pregnancy Hypertension

Article

Dec 1977
Clin Obstet Gynaecol

I.A. BROSENS

Cytokines and endothelial cell biology

Article

Apr 1990

Pregnancy-related hypertension

Article

Jan 2004

James M Roberts

Lipoprotein metabolism in pregnancy

Article

Jan 1992

CHEMISTRY OF OXIDATION OF LOW DENSITY LIPOPROTEINS

Chapter

Dec 1991

Vascular Changes in the Decidua Associated with Eclamptogenic Toxemia of Pregnancy

Article

Dec 1950

Patients with preeclampsia develop agonistic autoantibodies against the angiotensin AT(1) receptor.

Article

Sep 1997

Chesley's Hypertensive Disorders in Pregnancy

Book

Jan 2009

Hypertensive disorders remain one the major causes of maternal and fetal morbidity and death. It is also a leading cause of preterm birth now known to be a risk factor in remote cardiovascular disease. Despite this the hypertensive disorders remain marginally studied and management is often controversial. Chesley's Hypertensive Disorders in Pregnancy, remains one of the beacons to guide this field, recognized for its uniqueness and utility. The Third Edition continues this tradition, focusing on prediction, prevention, and management for clinicians, and is an essential reference text for clinical and basic investigators alike. Differing from other texts devoted to preeclampsia, it covers the whole gamut of high blood pressure, and not just preeclampsia. NEW TO THE THIRD EDITION: * New chapters focusing on recent discoveries in angiogenesis, auto-antibodies and other recent immunological findings, imaging in eclampsa, animal models - where considerable progress has emerged since the previous edition * Extensive updates to chapters on epidemiology, etiological considerations, pathophysiology, prediction, prevention, and management * Systematic reviews and metanalysis of trials regarding prediction and antihypertensive treatment * Discussions on the emerging roles of metabolic syndrome and obesity and the increasing incidence of preeclampsia * Epodemiological coverage of preeclampsia as a risk factor for future metabolic and cardiovascular disease that permits early intervention and life style changes

Status of human placental lipid peroxidation, superoxide dismutase and catalase during pregnancy-induced hypertension (PIH)

Article

Jan 1995

The level of lipid peroxidation in terms of malonaldialdehyde formation and free radical scavenging enzymes i.e. superoxide dismutase and catalase were estimated in whole homogenate and subcellular fractions in placental tissue obtained from 15 normal pregnant females and 13 patients of pregnancy induced hypertension (PIH) syndrome. A marked increase in malonaldialdehyde with concomitant decrease in superoxide dismutase and catalase levels was observed. Thereby indicating the involvement of free radicals in PIH.

Preeclampsia-Eclampsia, in Chesley's Hypertensive Disorders in Pregnancy 2nd (eds)

Article

Jan 1999

J.C. Hauth

The discovery of prostacyclin (PGX): A fresh insight into arachidonic acid metabolism

Article

Dec 1977

Rabbit aorta contracting substance (RCS) released from guinea-pig lungs has been identified as a mixture of prostaglandin endoperoxides and thromboxane A 2 . Thromboxane A 2 is a vasoconstrictor and a potent inducer of platelet aggregation. It is sunthesised by an enzyme located in the microsomal fraction of platelets and its generation is inhibited by imidazole.

The relation between hydatid moles, relative ischemia of the gravid uterus, and the placental origin of eclampsia

Article

Jan 1939
AM J OBSTET GYNECOL

E.W. Page

Fasting serum triglycerides, free fatty acids and malondialdehyde are increased in preeclampsia, are positively correlated, and decrease within 48 hours postpartum.

Article

Mar 1996
J Soc Gynecol Investig

C Hubel

Invited Review Free Radicals in Disease Processes: A Compilation of Cause and Consequence

Article

Jan 1993

Lipid peroxidation in biomembranes

Article

Dec 1989
FREE RADICAL BIO MED

Valerian E Kagan

The Placental Bed

Article

Jan 1996

R Pijnenborg

Objectives: To review critically published data concerning fetalmdash;maternal interaction at the placental bed level in normal and complicated pregnancies. Emphasis is placed on the adaptive changes of the uteroplacental vasculature of the placental bed. Methods: Histopathological and immunohistochemical data form the basis of this review. The relevance of recent studies on cultured trophoblast is considered in the light of histological findings. Results: The findings of recent experimental studies on invasive processes and trophoblastmdash;extracellular matrix interaction relate mainly to interstitial trophoblast, since no in vitro model is available for the study of vascular changes. The endovascular pathway of vascular invasion is emphasized, and mechanisms of arterial wall destruction need to be reconsidered since vascular disorganization and disruption may precede trophoblast invasion. There is a need for blood flow studies in relation to histopathological findings. Currently the role of various cytokines in trophoblast-maternal interaction is being intensively investigated, since disturbances in the cytokine network may be responsible for the inhibition of trophoblast invasion in complicated pregnancies. Conclusions: Various new techniques have led to a better insight of trophoblast invasion and its regulation. It is important that these should be interpreted in the context of histological reality as observed in the placental bed.

Fasting Serum Free Fatty Acids and Triglycerides are Increased Before 20 Weeks of Gestation in Women who Later Develop Preeclampsia

Article

Jan 1994

Objective: The null hypothesis of this study was that there was no difference in fasting serum concentrations of free fatty acids (FFA) and triglycerides (TG) before 20 weeks of gestation in women who later develop preeclampsia, compared to women with uneventful pregnancies. Methods: Healthy primigravida, n = 510, provided fasting blood samples at 16-18 weeks of gestation. Nineteen of these later developed preeclampsia. Nineteen matched controls were selected from the remaining 491 individuals. Blood samples were also obtained from 16 patients with manifest preeclampsia and from 16 control women with uncomplicated pregnancies. Concentrations of FFA and TG, and the lipolytic activity in maternal serum were measured. Results: In patients with manifest preeclampsia, serum levels of FFA and TG, and lipolytic activity were significantly increased compared to women with normal pregnancies. The group of 19 women who later developed preeclampsia had higher serum FFA and TG concentrations at 16-18 weeks of gestation compared to a matched control group: FFA 0.50 0.15 vs. 0.34 0.11 mmol/L (P < 0.001) and TG 1.3 0.5 vs. 0.9 0.3 mmol/L (P = 0.003). Conclusion: We provide for the first time evidence that fasting serum free fatty acids and triglycerides are increased before 20 weeks of gestation in women who later develop preeclampsia.

Current topic: pre-eclampsia and the placenta

Article

Jul 1991

Christopher W Redman

An ultrastructural study of utero placental arteries in hypertensive and normotensive pregnancy and fetal growth retardation

Article

Jul 1981
BJOG-INT J OBSTET GY

Uteroplacental spiral arteries in placental bed biopsies and placentas from 80 pregnancies were studied by light and electron microscopy; of these 30 were complicated by fetal growth retardation (less than 10th centile) and 45 by hypertension during pregnancy. The physiological changes of the spiral arteries and the vascular pathology present in hypertensive pregnancy and fetal growth retardation were investigated. In normotensive pregnancies complicated by fetal growth retardation, the physiological changes of pregnancy frequently did not extend beyond the decidual segments of the utero-placental arteries. In pregnancies complicated by pre-eclampsia, the physiological changes of pregnancy were not always restricted to the decidual segments of the utero-placental arteries. Athero-matous-like lesions of similar morphology were found in spiral arteries from both normotensive and hypertensive pregnancies complicated by fetal growth retardation. No arteriopathy was found which was specific for pre-eclampsia.

Low-density lipoprotein size decreases during normal pregnancy in association with triglyceride increases

Article

Sep 1998
J Soc Gynecol Investig

OBJECTIVE: To characterize the changes in low-density lipoprotein (LDL) peak particle diameter (diameter of the predominant LDL subclass) in relation to changes in serum triglyceride concentration during successive stages of normal gestation and postpartum. METHODS: Nonfasting venous blood was obtained longitudinally during and after uncomplicated primiparous pregnancy from 10 nonsmoking women with no history of metabolic disorders. Plasma LDL diameter was determined by nondenaturing polyacrylamide gel electrophoresis. Serum concentrations of total cholesterol, triglyceride, apolipoprotein B, apolipoprotein A-I, and LDL-cholesterol were measured. Gestational changes were analyzed by one-way repeated-measures analysis of variance and the paired multiple comparison Student-Newman-Keuls test. Pearson coefficients were computed for correlation of serum lipids and LDL diameter. Results: Low-density lipoprotein diameter decreased progressively with advancing gestation, evident by 16-20 weeks relative to 5-12 weeks. Seven of 10 cases were subclass pattern B (diameter less than 255 Angstrom or more) by 6-12 weeks with concentrations of serum triglyceride (r = -.61, P < .0001), apo B (r = -.66, P < .0001), cholesterol (r = - .53, P < .001), LDL cholesterol (r = -.45, P < .005), and apo A-I (r = -.39, P < .02). CONCLUSION: Gestational triglyceride increases are accompanied by progressive decreases in LDL diameter in a majority of cases. These changes undergo reversal postpartum and therefore are transient. Small, dense LDL particles have a number of properties capable of altering vascular function. However, the consequences of the gestational LDL size decrease for maternal and fetal metabolism remain unknown. Copyright (C) 1998 by the Society for Gynecologic Investigation.

Women with a history of eclampsia manifest dyslipidemia during later Life

Article

Jan 1998
J Soc Gynecol Investig

Genetic and familial predisposition to eclampsia and preeclampsia in a defined population

Article

Jun 1991

Peroxynitrite production from bovine aortic endothelial cells

Article

Nov 1993
FREE RADICAL BIO MED

Neil W Kooy

Plasma Nitric Oxide Levels in Pregnant Patients with Preeclampsia and Essential Hypertension

Article

Feb 1996
GYNECOL OBSTET INVES

Nitric oxide (NO) production may be an important causal factor in hypertensive disorders during pregnancy. The plasma concentrations of NO2––+NO3––, stable metabolites of NO, were measured in 70 nonpregnant women, 323 normotensive pregnant women, 23 pregnant patients with preeclampsia, and 7 pregnant patients with essential hypertension. The normotensive women had higher plasma concentrations (30.0 ± 0.6 μmol/l) than nonpregnant women (18.3 ± 1.0 μmol/l; p < 0.0001). The plasma concentrations in the patients with preeclampsia (45.6 ± 2.3 μmol/l) were higher than in the normotensive women (30.3 ± 1.0 μmol/l; p < 0.0001) and were correlated with the systolic blood pressure (r = 0.442; p < 0.05). However, pregnant patients with underlying essential hypertension had significantly lower plasma concentrations (19.1 ± 3.0 μmol/l; p < 0.005). These findings suggest that NO contributes to maternal vasodilation, the maintenance of uterine quiescence, and the pathogenesis and clinical features of hypertensive disorders during pregnancy.

Antibodies to Oxidized Low-Density Lipoprotein, Cardiolipin, and Phosphatidyl Serine Fail to Predict the Risk of Preeclampsia

Article

Jul 2009

Objective: In view of the data that high levels of antibodies to oxidized low-density lipoprotein (LDL), cardiolipin, and phosphatidyl serine are present in plasma of women with established preeclampsia, we studied whether the risk of preeclampsia could be predicted by these antibodies. Methods: In our prospective trial, blood samples were drawn from 722 healthy nulliparous women at the first prenatal checkup between 10 and 17 gestational weeks. Twenty of them (2.8%) developed established preeclampsia (blood pressure elevation > 140/100 mm Hg and proteinuria 0.3-8.3 g/24 h). As a control group we studied 42 women who remained normotensive during pregnancy and delivery, and postpartum. Results: The levels of antibodies to oxidized LDL, cardiolipin, or phosphatidyl serine in women later developing preeclampsia did not differ from levels in women who remained normotensive. Conclusion: We conclude that antibodies to oxidized low-density lipoprotein, cardiolipin, and phosphatidyl serine fail to predict the risk of preeclampsia.

Trophoblast function in normal and preeclamptic pregnancy

Article

May 1996
Fetal Matern Med Rev

James C Cross

Preeclampsia (PE) is a common disease of pregnancy that affects women particularly in their first pregnancies. Current estimates suggest that between 7 and 10% of pregnancies may be complicated by PE. Despite considerable research and medical efforts, the incidence of the disease has not changed substantially in the last century. In severe cases the disease may be life-threatening and is associated with high neonatal mortality and morbidity. Furthermore, therapy is often ineffective and at best treats the disease symptoms rather than the aetiology. One reason for the lack of progress may be that while the disease is generally agreed by most to be due to abnormal implantation and development of the placenta (events which happen in the first trimester) most research efforts have focused on managing and understanding the maternal disease. Since the disease typically appears in the last trimester, many weeks after the likely start of the pathology, it has been difficult to understand the progression of events. However, this picture has improved recently. The purpose here is to review how placental development is affected in PE and describe new insights into the causes. It is hoped that an understanding of the pathogenesis of the placental defects in PE will lead to new efforts towards early diagnosis, before the onset of clinical symptoms, as well as new treatments for these lesions.

High Altitude and hypertension during pregnancy

Article

Jan 1995
AM J HUM BIOL

Hypertensive complications of pregnancy are more common at high than low altitudes. Hypertension in pregnancy is associated with increased maternal and fetal morbidity and mortality; thus natural selection may be operating against women who develop the disorder and their infants. It has long been hypothesized that chronic hypoxia due to residence at high altitude predisposes women to develop hypertension during pregnancy. Prior studies indicate that maternal adaptation to pregnancy is altered by residence at high altitude such that some physiological characteristics of women pregnant at high altitude resemble those of women who develop hypertension during pregnancy at low altitude. This paper reviews data from studies, conducted over the past decade, which support a relationship between chronic hypoxia and hypertension during pregnancy. The results suggest that both the requirements for successful adaptation to high altitude, as well as the effect of lowered PO2 during pregnancy, may contribute to the development of hypertension during pregnancy. © 1995 Wiley-Liss, Inc.

Antibodies against copper‐oxidised and malondialdehyde‐modified low density lipoproteins in pre‐eclamptic pregnancies

Article

Oct 1998
BJOG-INT J OBSTET GY

Objective To measure auto-antibodies against oxidatively modified low density lipoprotein (LDL) in pre-eclamptic pregnancies using two different techniques. Design Clinical study comparing pre-eclamptic and normal pregnancies. Setting Tampere University Hospital, Finland. Population Twenty-one primigravidae with pre-eclampsia and 13 healthy, normotensive primigravidae as controls. Methods The serum titers of antibodies against both malondialdehyde-modified and copper-oxidised LDL (MDA-LDL and copper-ox LDL) were analysed and related to parameters reflecting the severity of pre-eclampsia. Results There was a positive correlation (r= 0.58) between antibodies against MDA-LDL and copper-ox LDL in women with pre-eclampsia but not in healthy pregnant controls. The antibody levels against copper-ox LDL, but not against MDA-LDL, were higher in women with pre-eclampsia than in women with a normal pregnancy (P < 0.01). While the antibody titers against copper-ox LDL did not correlate with any parameter reflecting the severity of pre-eclampsia, those against MDA-LDL showed a positive correlation with the level of diastolic blood pressure (r= 0.54) and a negative correlation with platelet count (r= 461) in women with pre-eclampsia. Conclusions There are increased titers of serum autoantibodies against copper-oxidised LDL in pre-eclampsia, which may reflect enhanced lipid peroxidation involving circulating lipoproteins.

Small lowdensity lipoproteins and vascular cell adhesion molecule (VCAM-1) are increased in association with hyperlipidemia in preeclampsia

Article

Oct 1998
METABOLISM

The pregnancy disorder preeclampsa is characterized by endothelial cell dysfunction that may be promoted by abnormal increases in circulating lipids, particularly triglycerides and free fatty acids. Serum triglyceride concentration is a major regulatory determinant of low-density lipoprotein (LDL) size and density distribution. Smaller, denser LDL particles have several intrinsic properties capable of inducing endothelial dysfunction. The present nested, case-control study of gestationally matched preeclamptic and normal pregnant women tested the hypothesis that hypertriglyceridemia in preeclampsia is accompanied by decreases in LDL peak particle diameter (predominant LDL size). Plasma LDL peak particle diameter was determined by nondenaturing 2% to 16% polyacrylamide gel electrophoresis. Correlations of LDL diameter with the concentration of serum triglycerides, free fatty acids, total cholesterol, LDL-cholesterol, and apolipoprotein B (apo B) were determined. In the same individuals, we measured serum concentrations of a marker of vascular dysfunction previously reported to be increasd in preeclampsia, soluble vascular cell adhesion molecule-1 (VCAM-1), and examined the association of VCAM-1 with LDL diameter and serum lipids. LDL peak particle diameter was decreased in preeclampsia relative to normal pregnancy (P < .01). The LDL-cholesterol:apo B ratio, which frequently decreases with decreasing LDL diameter, was also decreased (P < .04). Triglyceride concentrations were increased in preeclampsia (P < .0002), and there was a significant inverse relationship between LDL peak particle diameter and triglycerides (r = −.55, P < .02). Serum soluble VCAM-1 concentrations were markedly increased in preeclampsia (P < .0003). Apo B (P < .004), free fatty acids (P < .01), total cholesterol (P < .01), and LDL-cholesterol (P < .02) were also increased. VCAM-1 correlated with apo B (r = .50, P < .03) and LDL-cholesterol (r = .50, P < .03), but showed no relationship with the LDL diameter, LDL-cholesterol:apo B ratio, or other lipids. We conclude that the predominance of smaller, denser LDL, a potential contributor to endothelial cell dysfunction, is a feature of preeclampsia. However, the serum VCAM-1 level, one indicator of endothelial involvement, may be influenced more by quantitative lipoprotein changes (serum apo B or LDL-cholesterol) than by LDL particle size.

Metabolism of very-low-density lipoprotein triglyceride by human placental cells: The role of lipoprotein lipase

Article

Jun 1992
METABOLISM

Several studies have shown lipoprotein lipase (LPL) activity in human placenta, but the quantitative significance and cellular specificity of LPL in this organ are unknown. The objective of this report is to investigate the metabolism of very-low-density lipoprotein triglycerides (VLDL-TG) by the placenta, the role of LPL in this process, and the types of cells involved. Placental cells were obtained by enzymatic digestion (collagenase, hyaluronidase, and DNA-ase) and separated on a 40% Percoll gradient. The trophoblasts were the predominant cell type (80% to 85% pure) isolated at d = 1.033 to 1.048 and macrophages were predominant at d = 1.077 to 1.100 (greater than 95% pure), as characterized by eight immunocytochemical assays using cell protein-specific monoclonal antibodies. Macrophages represented 50% to 60% of cells isolated, and trophoblasts, 40% to 50%. LPL activity was assessed by VLDL-TG hydrolysis in primary 3- to 4-day tissue culture. In a representative experiment, LPL activity (nmol fatty acids (FA)/mg protein/24 h) was 101.3 +/- 5.3 in macrophages and 29.9 +/- 6.5 in the predominant trophoblast cell types, with approximately 20% of these amounts incorporated and reesterified. VLDL-TG hydrolysis and cell lipid uptake in both placental cell types was essentially abolished by a monoclonal anti-LPL antibody. When compared with a model of hepatocytes (Hep G2 cells), the hydrolysis of VLDL-TG was almost undetectable in these cells. In contrast, free fatty acids (FFA) uptake by Hep G2 cells was fourfold to sixfold greater than that by macrophages and trophoblasts, respectively. In conclusion, macrophages and trophoblasts are the two predominant placental cells isolated by enzymatic digestion.(ABSTRACT TRUNCATED AT 250 WORDS)

Heterogeneous causes constituting the single syndrome of preeclampsia: A hypothesis and its implications

Article

Dec 1996
AM J OBSTET GYNECOL

The cause of preeclampsia remains elusive in spite of many attempts to understand its biologic characteristics and to characterize its predictors. We suggest that there are distinct origins of preeclampsia, each with its own pathologic characteristics and natural history. One genesis is the result of reduced placental perfusion, which we will call placental, and another results from maternal disorders preexisting (but sometimes not evident before) pregnancy. These preexisting maternal disorders comprise predisposing factors for cardiovascular disease such as hypertension, renal disease, overweight, and diabetes. A critical review of the epidemiologic and pathologic literature is presented, which supports the hypothesis that preeclampsia is the result of heterogeneous causes. The implications of this hypothesis are discussed, particularly its impact on the development of rules to predict the occurrence of preeclampsia. (Am J Obstet Gynecol 1996;175:1365-70.)

Increased Ascorbate Radical Formation and Ascorbate Depletion in Plasma from Women With Preeclampsia: Implications for Oxidative Stress

Article

Feb 1997
FREE RADICAL BIO MED

There is evidence that oxidative stress accompanies preeclampsia and plasma ascorbate concentrations are reported to be decreased in the disorder. We tested the hypothesis that an ascorbate-oxidizing activity is increased in plasma from women with preeclampsia relative to normal pregnancy. Electron paramagnetic resonance (EPR) spectroscopy was used to determine (1) plasma functional reserves of ascorbate and total thiols, (2) temporal changes in ascorbate and thiol concentrations during incubation of whole blood in vitro, and (3) ascorbate radical signal kinetics in plasma after equalization of ascorbate concentrations. High-pressure liquid chromatography (HPLC) was used to measure plasma α-tocopherol. Ascorbate concentrations were 50 % lower in preeclampsia relative to normal pregnancy plasma but thiols and α-tocopherol did not differ. The elapsed time prior to half-consumption of plasma ascorbate was decreased approximately three-fold during incubation of whole blood from preeclamptics. No concomitant decrease in thiols was evident. The initial ascorbate radical signal amplitude was greater in preeclampsia plasma and then, in contrast to normal pregnancy plasma, decreased progressively. The iron chelator, deferoxamine had no effect on plasma ascorbate radical formation. We conclude that an ascorbate-oxidizing activity is increased in preeclampsia plasma which might contribute to vascular dysfunction in the disorder.

Lipid hydroperoxides potentiate mesenteric artery vasoconstrictor responses

Article

Apr 1993
FREE RADICAL BIO MED

The aim of this study was to investigate the effects of lipid and organic hydroperoxides on vasomotor activity of isolated rat superior mesenteric arteries. Hydroperoxides did not elicit measurable responses in unstimulated (quiescent) mesenteric arteries. Contractile responses to potassium, however, were significantly potentiated by 13-(s)-hydroperoxylinoleic acid (range 3–54 μM). Potentiation of potassium responses by linoleic acid (18:2) and linolenic acid (18:3) was increased by pretreatment of the fatty acids with lipoxygenase (p < .01). Lipoxygenase alone had no contractile effects. Lipoxygenase-treated 18:2, tert-butyl hydroperoxide, and hydrogen peroxide augmented contractile responses to phenylephrine, but to a lesser degree than corresponding augmentation of potassium responses. Contractile responses to lipoxygenase-treated 18:3 were blunted by vitamin E (p < .02) and by nitroblue tetrazolium (p < .02), whereas catalase and mannitol had no effects, implicating lipid free radicals in the contractile response. Responses to lipid hydroperoxides were not significantly altered by prostaglandin inhibitors. Endothelial cell denudation significantly enhanced the contractile responses elicited by 13-(s)-hydroperoxylinoleic acid (p < .05), indicating that lipid hydroperoxides enhance agonist-induced contractions by a direct effect on the smooth muscle. These results support a hypothesized link between lipid peroxidation and development of altered vascular function. They further suggest that the vascular endothelium may play an important role in regulation of vasomotor responses to lipid hydroperoxides.

NADH/NADPH oxidase and vascular function

Article

Nov 1997
TRENDS CARDIOVAS MED

The vascular NADH/NADPH oxidase has been shown to be the major source of superoxide in the vessel wall. Recent work has provided insight into its structure and activity in vascular cells. This enzyme is involved in both vascular smooth muscle hypertrophy and in some forms of impaired endothelium-dependent relaxation. Because oxidative stress in general participates in the pathogenesis of hypertension and atherosclerosis, the enzymes that produce reactive oxygen species may be important determinants of the course of vascular disease. (Trends Cardiovasc Med 1997;7:301-307). © 1997, Elsevier Science Inc.

Vitamin C in Health and Disease

Article

Jan 1982

The hyperlipemia of pregnancy in normal and complicated pregnancies

Article

Feb 1979
AM J OBSTET GYNECOL

Alterations in the concentrations of the cholesterol and triglyceride moieties of lipoproteins separated by ultracentrifugation and precipitation methods were studied at frequent intervals throughout pregnancy and the puerperium in a group of 43 women. The plasma cholesterol concentration rose on the average by about 50 per cent, the major increase occurring in the second trimester. The plasma triglyceride concentration rose threefold, reaching its peak during the third trimester. All major lipoproteins participated in these changes: in very-low-density lipoproteins, both lipids rose in proportion to the ratio in nonpregnant women, but in low-density and high-density lipoproteins, the ratio of triglyceride to cholesterol rose. The triglyceride enrighment in low-density lipoproteins reflected the inclusion of intermediate-density lipoproteins (d 1.006 to 1.019). The occurrence of hypertension or pre-eclampsia led to a further increase in lipids in very-low-density lipoproteins. Hypercholesterolemia was greatest in women with pre-existing hypercholesterolemia, and women in the third pregnancy showed higher plasma cholesterol concentrations than women in the first pregnancy. Both cholesterol and triglyceride concentrations decreased significantly within 24 hours of delivery and this was reflected in all lipoproteins. However, while triglyceride levels continued to decrease rapidly returning to nonpregnant levels during the puerperium, cholesterol in low-density lipoprotein remained elevated for at least six to seven weeks post partum.

Changes of lipid peroxidation and superoxide dismutase activity in human placenta

Article

Nov 1979
AM J OBSTET GYNECOL

The oxygen radical may induce peroxidation of unsaturated fatty acids in vivo. We studied changes in superoxide dismutase (SOD) activity and lipid peroxidation using human placental tissue. Lipid peroxidation was marked in early stages (2 to 4 months) of gestation but decreased with growth and was very small by the end of pregnancy. The SOD activity of placental tissue in early gestation was approximately 250 to 500 U per gram of wet weight. The activity increased with growth of the placenta and reached a level of 400 to 1,500 U per gram of wet weight by the end of gestation. These results for SOD activity suggest that the oxygen requirement in the placenta at early stages of gestation is low compared with that at the end of gestation.

Pregnancy, outcome as related to hypertension, edema, and proteinuria

Article

Feb 1976
Perspect Nephrol Hypertens

Clinical variables of blood pressure, proteinuria, edema, and maternal weight have been studied extensively, with particular reference to associated adverse fetal and infant outcomes. The levels of these variables, as well as their relative patterns of change with advancing pregnancy, were investigated by several analytic methods. It was determined that diastolic blood pressure and proteinuria, alone and in combination, profect on fetal and infant outcomes to enable us to create an empirical classification of gravidas whose fetuses were probably at risk. The results must be considered preliminary in view of the fact that the work is still in progress.

The ultrastructure of acute atherosis in hypertensive pregnancy

Article

Oct 1975
AM J OBSTET GYNECOL

Acute atherosis of the myometrial segments of the uteroplacental arteries from pre-eclamptic pregnancies was studied by electron microscopy. The lesions in their early stages are characterized by endothelial damage, insudation of plasma constituents into the vessel wall, proliferation of myointimal cells, and medial necrosis. Fat acculumation is seen first in myointimal cells and, later, macrophages engulf the lipid-rich debris released from disintegrating myogenic foam cells. Gross endothelial damage, massive intramural fibrin deposition, luminal thrombosis, and vessel rupture with hemorrhage are epiphenomena.

Sera antioxidant activity in uncomplicated and preeclamptic pregnancies

Article

Jul 1992
OBSTET GYNECOL

Uncontrolled lipid peroxidation may play an important role in the pathophysiology of preeclampsia by causing vascular endothelial cell dysfunction. Sera contain antioxidant mechanisms that serve to control lipid peroxidation. We tested the hypothesis that the sera antioxidant protective mechanisms are diminished in women with preeclampsia. Blood samples were collected within 24 hours of delivery (pre-delivery) and by 24 hours postpartum (post-delivery) from women with preeclampsia (N = 8) and from matched controls with uncomplicated pregnancies (N = 8). Antioxidant activity was determined by the ability of sera to inhibit autoxidation of a standardized brain homogenate. Lipid peroxidation of both brain homogenate and sera was analyzed by high-pressure liquid chromatography using the amount of malondialdehyde present as an indicator of peroxidation. Pre-delivery sera from women with preeclamptic pregnancies had one-half the antioxidant activity of sera from women with uncomplicated pregnancies (42 versus 90%; P less than .01). Malondialdehyde values alone were not significantly different between the groups in either the pre-delivery or post-delivery samples. When using a ratio to evaluate the relative balance between lipid peroxidation and antioxidant activity, pre-delivery samples from women with preeclampsia had over a twofold increase in this ratio compared with samples from uncomplicated pregnancies. In conclusion, in contrast to women with uncomplicated pregnancies, women with preeclampsia have antioxidant activity that is markedly reduced by late gestation. For women with preeclampsia, this may result in a greater potential for endothelial oxidative damage.

Free radicals, antioxidants, and human disease: Where are we now?

Article

Jul 1992
J Lab Clin Med

Non-invasive measures of oxidative stress status in human

Article

Feb 1991
FREE RADICAL BIO MED

Although oxidative stress is thought to be involved in the pathophysiology of several diseases and aging, it is not routinely measured in clinical diagnosis. This is at least partly because accepted and standardized methods for measuring oxidative stress in humans are not yet established. One of the greatest needs in the field of free radical biology is the development of reliable methods for measuring oxidative stress status (OSS) in humans. A listing of some analytical approaches to measuring oxidative stress is provided as well as a listing of some noninvasive techniques that have been used in humans.

Functional differences in human neutrophils isolated pre- and post-prandially

Article

Aug 1991

Activated polymorphonuclear leukocytes have been associated with neoplasia, atherogenesis and reperfusion injury. Since some of these conditions are also correlated with dietary fat, we examined the functional characteristics of leukocytes isolated from subjects before and after consumption of a lipid-rich meal. There was up to 2-fold greater superoxide generation in response to agonists in leukocytes obtained post-prandially; the maximum increase was observed about 4 h after eating and followed the peak (2-4 h) in serum triglycerides. Neutrophils isolated post-prandially also exhibited impaired chemotaxis and defective bacterial killing, but normal phagocytosis. These findings provide a new variable that should be considered in studies of leukocytes.

Low superoxide scavenging activity associated with enhanced superoxide generation by monocytes from male hypertriglyceridemia with and without diabetes

Article

Oct 1991
Atherosclerosis

To investigate the mechanism of increased superoxide (O2-) generation by monocytes from patients with hypertriglyceridemia, superoxide scavenging activity (SSA) and O2- generation by monocytes were determined concomitantly employing an electron spin resonance/spin trapping method and 2-methyl-6-[p-methoxyphenyl]-3,7-dihydroimidazo [1,2-a]-pyrazin-3-one (MCLA)-dependent chemiluminescence, respectively. Peripheral monocytes were separated by the adherent methods from the following four male groups: normal control, diabetes alone (DM), diabetes with hypertriglyceridemia (DM + HTG) and hypertriglyceridemia alone (HTG). Monocytes were stimulated by 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (PMA) or opsonized zymosan (OZ). O2- generation by monocytes upon stimulation was enhanced in HTG and HTG + DM but not in DM as compared to that in normal controls. The mean value of SSA in monocytes was similar among the 4 groups. When the relationship was analyzed using various parameters, a significant positive relationship was found between O2- generation and the plasma triglyceride level; a significant negative correlation was found between SSA and both the O2- generation and the plasma triglyceride level. In the in vitro system, the SSA in monocytes decreased significantly after the the stimulation by either of PMA or OZ. The results indicate that the decrease of SSA in monocytes may originate from the enhanced in vivo O2- generation and is responsible for the enhanced O2- release against the stimuli in hypertriglyceridemia. These abnormal functions of monocytes may in part accelerate the development of atherosclerosis.

Endothelin, elastase, and endothelial dysfunction in pre-eclampsia

Article

Apr 1991

Pober JS, Cotran RSCytokines and endothelial cell biology. Physiol Rev 70:427-451

Article

May 1990

Oxidative Stress in the Pathogenesis of Preeclampsia

Abstract

No full-text available

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