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Hydroxytyrosol (HT) effect on intercellular adhesion molecule-1 (ICAM-1) and P-selectin expression: immunohistochemical analysis of ICAM-1 of sham + vehicle (A), caerulein + vehicle (B) and caerulein + HT (5 mg/kg) (C) administration. Graphical quantification of ICAM-1 expression (D). Immunohistochemical analysis of P-selectin of sham + vehicle (E), caerulein + vehicle (F) and caerulein + HT (5 mg/kg) (G) administration. Graphical quantification of P-selectin expression (H). For the analyses, n = 5 animals from each group were employed. A p-value < 0.05 was considered significant. *** p < 0.001 vs. sham + vehicle, ### p < 0.001 vs. caerulein + vehicle.
Source publication
Acute pancreatitis is a severe abdominal pathology often associated with several complications including gut dysfunction. Oxidative stress is one of the most important pathways involved in this pathology. Hydroxytyrosol (HT), a phenolic compound obtained from olive oil, has shown anti-inflammatory and antioxidant properties. We evaluated the effect...
Contexts in source publication
Context 1
... are involved in the pathogenesis of systemic inflammation and multiple organ failure in acute pancreatitis [57]; therefore, immunohistochemical analysis to evaluate their expression was performed. Increased adhesion molecule expression (ICAM-1 and P-selectin) was detected in samples collected from vehicle-treated mice ( Figure 7B,D,F,H, respectively), as compared to sham samples ( Figure 7A,D,E,H, respectively). HT administration (5 mg/kg) reduced both ICAM-1 ( Figure 7C,D) and P-selectin ( Figure 7G,H) expression in colon tissue. ...
Context 2
... are involved in the pathogenesis of systemic inflammation and multiple organ failure in acute pancreatitis [57]; therefore, immunohistochemical analysis to evaluate their expression was performed. Increased adhesion molecule expression (ICAM-1 and P-selectin) was detected in samples collected from vehicle-treated mice ( Figure 7B,D,F,H, respectively), as compared to sham samples ( Figure 7A,D,E,H, respectively). HT administration (5 mg/kg) reduced both ICAM-1 ( Figure 7C,D) and P-selectin ( Figure 7G,H) expression in colon tissue. ...
Context 3
... adhesion molecule expression (ICAM-1 and P-selectin) was detected in samples collected from vehicle-treated mice ( Figure 7B,D,F,H, respectively), as compared to sham samples ( Figure 7A,D,E,H, respectively). HT administration (5 mg/kg) reduced both ICAM-1 ( Figure 7C,D) and P-selectin ( Figure 7G,H) expression in colon tissue. ...
Context 4
... adhesion molecule expression (ICAM-1 and P-selectin) was detected in samples collected from vehicle-treated mice ( Figure 7B,D,F,H, respectively), as compared to sham samples ( Figure 7A,D,E,H, respectively). HT administration (5 mg/kg) reduced both ICAM-1 ( Figure 7C,D) and P-selectin ( Figure 7G,H) expression in colon tissue. ...
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Citations
... When suffering from oxidative stress, nuclear factor erythroid 2-related factor 2 (Nrf2) binds to the antioxidant response element gene to up-regulate the expression of antioxidant gene [226]. Hydroxytyrosol, an antioxidant phenol, scavenges free radicals to improve CER-AP and AP-related gut injury by activating Nrf2 pathway in vivo [227], indicating Nrf2 is an antioxidative target for AP. Pre-inhalation of H 2 showed protective effect in CER-induced AP by annihilating excessive ROS [228]. ...
Acute pancreatitis (AP) is one of the most common gastrointestinal tract diseases with significant morbidity and mortality. Current treatments remain unspecific and supportive due to the severity and clinical course of AP, which can fluctuate rapidly and unpredictably. Mitochondria, cellular power plant to produce energy, are involved in a variety of physiological or pathological activities in human body. There is a growing evidence indicating that mitochondria damage-associated molecular patterns (mtDAMPs) play an important role in pathogenesis and progression of AP. With the pro-inflammatory properties, released mtDAMPs may damage pancreatic cells by binding with receptors, activating downstream molecules and releasing inflammatory factors. This review focuses on the possible interaction between AP and mtDAMPs, which include cytochrome c (Cyt c), mitochondrial transcription factor A (TFAM), mitochondrial DNA (mtDNA), cardiolipin (CL), adenosine triphosphate (ATP) and succinate, with focus on experimental research and potential therapeutic targets in clinical practice. Preventing or diminishing the release of mtDAMPs or targeting the mtDAMPs receptors might have a role in AP progression.
... A Super-Signal West Pico Chemiluminescent Substrate (Pierce) enhanced chemilumi-nescence detection system reagent was used to detect the signals [40]. The relative expression of the protein bands was measured using densitometry and standardized to β-actin and Lamin A/C levels using Bio-Rad ChemiDoc XRS software [41]. Blot signal images were input into analysis software (Image Quant TL, v2003). ...
... Current ndings demonstrated that Nrf2/HO-1 antioxidant signaling pathway is an important protective factor against AP-induced intestinal barrier dysfunction. Upregulation of Nrf2/HO-1 expression can accelerate intestinal vascular perfusion and the restoration of intestinal barrier dysfunction [ 33][34] . MDA and ROS are representative markers of oxidative stress, which can re ect oxidative stress damage to a certain extent and are also useful to appreciate the severity of AP in the very early stage. ...
Background
Severe intestinal barrier dysfunction occurs in the early stages of acute pancreatitis (AP) and plays a significant role in the mechanism of pancreatic necrosis as well as multiple organ failure in AP. Our study aims to explore the therapeutic effects and underlying mechanisms of ulinastatin (UTI) in improving intestinal barrier dysfunction associated with L-arginine-induced AP in rats.
Methods
We randomly assigned experimental rats into three subgroups (n = 10 per group): a control group, an AP group, and an AP + UTI (10000 U/kg) group. We assessed serum levels of amylase, lipase, intestinal fatty acid binding protein (I-FABP), and diamine oxidase (DAO). Additionally, we conducted pathological examinations on pancreatic and terminal ileal tissues. Laser Doppler blood flow meters were used to evaluate blood perfusion in the terminal ileal tissue. We observed the mucosal ultrastructure in the terminal ileal tissue using a transmission electron microscope (TEM). Furthermore, we determined protein and mRNA levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in terminal ileal tissue through western blot and quantitative reverse transcription PCR (qRT-PCR) analysis. We also measured the activities of peroxides and antioxidants in terminal ileal tissue.
Results
Compared to the AP group, the AP + UTI group exhibited significant reductions in serum levels of amylase, lipase, I-FABP, and DAO, along with alleviated pathological injuries in both pancreatic and terminal ileal tissues. Furthermore, after UTI treatment, we observed improvements in blood perfusion, mucosal ultrastructure, and permeability in the terminal ileal tissue. Additionally, UTI treatment led to notable increases in protein and mRNA levels of Nrf2 and HO-1 in the terminal ileal tissue. This resulted in a significant decrease in peroxide levels, including MDA and ROS, along with a marked increase in the activities of antioxidants, including glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST), and total sulfhydryl (T-SH).
Conclusions
This study is the first to prove that UTI alleviates AP and improves AP-associated intestinal barrier dysfunction by promoting antioxidative stress through the activation of the Nrf2/HO-1 pathway.
... The TBARS test was used to assess lipid peroxidation by measuring MDA levels at 535 nm [61]. SOD activity was evaluated as already described [62] and is expressed as U/g protein [63]. ...
Endometriosis is a chronic disease characterized by pelvic inflammation. This study aimed at investigating the molecular mechanisms underlying the pathology and how they can be modulated by the administration of a natural compound, Actaea racemosa (AR). We employed an in vivo model of endometriosis in which rats were intraperitoneally injected with uterine fragments from donor animals. During the experiment, rats were monitored by abdominal high-frequency ultrasound analysis. AR was able to reduce the lesion's size and histological morphology. From a molecular point of view, AR reduced hyperproliferation, as shown by Ki-67 and PCNA expression and MAPK phosphorylation. The impaired apoptosis pathway was also restored, as shown by the TUNEL assay and RT-PCR for Bax, Bcl-2, and Caspase levels. AR also has important antioxidant (reduced Nox expression, restored SOD activity and GSH levels, and reduced MPO activity and MDA levels) and anti-inflammatory (reduced cytokine levels) properties. Moreover, AR demonstrated its ability to reduce the pain-like behaviors associated with the pathology, the neuro-sensitizing mediators (c-FOS and NGF) expression, and the related central astrogliosis (GFAP expression in the spinal cord, brain cortex, and hippocampus). Overall, our data showed that AR was able to manage several pathways involved in endometriosis suppression.
... Specific labeling was identified with a biotin-conjugated goat anti-rabbit IgG and avidinbiotin peroxidase complex (Vector Laboratories, Burlingame, CA, USA) [69]. The stained sections were observed using a Leica DM6 microscope (Leica Microsystems S.p.A., Milan, Italy), following a typical procedure [70,71]. ...
Diet can modulate the different stages of inflammation due to the presence of bioactive compounds such as polyphenols. Apples are a great source of phenolic compounds that show anti-inflammatory and antioxidant properties, and these might be used as a dietary supplement and/or functional element in the treatment of chronic inflammatory illnesses. The aim of our study was to evaluate the anti-inflammatory and antioxidant actions of thinned apple polyphenol (TAP) extracts in a model of paw edema. The experimental model was induced in rats via subplantar injections of 1% λ-Carrageenan (CAR) in the right hind leg, and TAP extract was administered via oral gavage 30 min before and 1 h after the CAR injection at doses of 5 mg/kg and 10 mg/kg, respectively. The inflammatory response is usually quantified by the increase in the size of the paw (edema), which is maximal about 5 h after the injection of CAR. CAR-induced inflammation generates the release of pro-inflammatory mediators and reactive oxygen species (ROS). Furthermore, the inflammatory state induces the pain that involves the peripheral nociceptors, but above all it acts centrally at the level of the spinal cord. Our results showed that the TAP extracts reduced paw histological changes, neutrophil infiltration, mast cell degranulation, and oxidative stress. Additionally, the oral administration of TAP extracts decreased thermal and mechanical hyperalgesia, along with a reduction in spinal microglia and the markers of nociception. In conclusion, we demonstrate that TAP extract is able to modulate inflammatory, oxidative, and painful processes, and is also useful in the treatment of the symptoms associated with paw edema.
... The innate immune activation and the acinar cell inflammatory signaling play a pivotal role in the pathogenesis of AP, with the need to balance pro-inflammatory cytokines/chemokines (Tumor necrosis factor, TNF-α; interleukin-1, IL-1) and anti-inflammatory or regulatory molecules (IL-10). Intestinal dysfunction and secondary inflammatory issues aggravate AP retroactively and are prodromes of systemic complications [26]. So, changes in the microcirculation, gut permeability/motility, bacterial translocation, and activation of the gut-associated lymphoid tissue, variously present in IBD patients, were postulated as factors promoting pancreatic inflammation. ...
... The oxidative stress and the lysosomal damage/dysfunction, generally linked to neurodegeneration and IBD in humans, may represent another important AP pathogenetic pathway. Using antioxidant substances [26,30] and targeting lysosomes for cell death induced by lysosomal membrane permeabilization are considered additional potential strategies in recent studies. Interestingly, Sudhakar et al. showed that loss of a carbohydratebinding intracellular protein, galectin 9 (Gal-9), in mice causes unstable lysosomes in autophagy-active selectively in intestinal and pancreatic cells at the steady state, with compromising autophagy and consequent increased susceptibility to disease pathogenesis. ...
The relationship between chronic intestinal disease, including inflammatory bowel disease (IBD) and celiac disease (CelD), and pancreatic disorders has been little investigated. Although an increased risk of acute pancreatitis (AP), exocrine pancreatic insufficiency with or without chronic pancreatitis, and chronic asymptomatic pancreatic hyperenzymemia have been described in these patients, the pathogenetic link remains unclear. It may potentially involve drugs, altered microcirculation, gut permeability/motility with disruption of enteric-mediated hormone secretion, bacterial translocation, and activation of the gut-associated lymphoid tissue related to chronic inflammation. In addition, the risk of pancreatic cancer seems to be increased in both IBD and CelD patients with unknown pathogenesis. Finally, other systemic conditions (e.g., IgG4-related disease, sarcoidosis, vasculitides) might affect pancreatic gland and the intestinal tract with various clinical manifestations. This review includes the current understandings of this enigmatic association, reporting a clinical and pathophysiological overview about this topic.
... Oxidative stress is severely elicited following the increase in the production of ROS and irregularity created in the antioxidant capacity balance (Abdelzaher et al., 2020;Sindhu et al., 2005;Vaziri et al., 2007). It has been assumed that free-radical oxygen scavengers have a clinically protective effect and could be efficient in patients with AP (Fusco et al., 2020;Swentek, Chung, Ichii, 2021;Zhang et al., 2012). Oxidative stress caused by acute pancreatitis accelerates the inflammatory process and disturbs cellular metabolism regulation by activating more complex inflammatory processes, leading to cell death (Gukovsky et al., 2013;Pérez et al., 2015). ...
Acute pancreatitis (AP) is a life-unpleasant situation with contradictory and inadequate
treatments. In this regard, the present study evaluated the effect of the possible pretreatment of
lipase-pancreatin on L-arginine-induced AP. Forty adult mice were selected and divided into
five groups: I) control group, II and III) AP groups (i.p.) receiving L-arginine of 2×300 and
2×400 mg/100 g body weight (b.w.), IV) AP (2×300 L-arginine) group + pancreatin (mice were
i.p. injected by 350 U-lipase), and V) AP (2×400 L-arginine) group + pancreatin (mice were
i.p. injected by 350 U-lipase). All AP groups displayed a significant increase in serum levels of
ALT, AST, TBARS, and TNF-alpha compared to the control group. Moreover, pancreatic tissue
edema, inflammation, and vacuolization of acinar cells were significantly higher in the untreated
L-arginine group compared to the control and pancreatin groups. Conversely, the diameter of
pancreatic islets significantly declined after induction of pancreatitis compared with control
and pancreatin groups. Pancreatin treatment can be used in pancreatic dysfunction, however,
this medicine showed no protective effect against L-arginine-induced AP in the mouse model.
... It boosted cellular defenses against ROS by boosting the Nrf2/HO-1 pathway. Nrf2 oversees genes that code for endogenous antioxidant enzymes, redox balance factors, and stress response proteins [28,43,44]. It specifically stimulated phase II detoxification enzymes such as CAT, SOD, and GSH. ...
... To ensure that the quantities of protein were similar, the membranes were additionally treated with an antibody against β-actin and Lamin (Santa Cruz Biotechnology, Dallas, TX, USA). Signals were detected using a Super-Signal West Pico Chemiluminescent Substrate (Biogenerica, Pedara, Italy) enhanced chemiluminescence detection system reagent [44]. The relative expression of the protein bands was measured using densitometry and was standardized to β-actin and Lamin levels using Bio-Rad ChemiDoc XRS 2.1.1 software [48]. ...
Alzheimer’s disease (AD) is the most common cause of dementia, and its prevalence rises with age. Inflammation and altered antioxidant systems play essential roles in the genesis of neurodegenerative diseases. In this work, we looked at the effects of MemophenolTM, a compound rich in polyphenols derived from French grape (Vitis vinifera L.) and wild North American blueberry (Vaccinium angustifolium A.) extracts, in a rat model of AD. Methods: For 60 days, the animals were administered with AlCl3 (100 mg/kg, orally) and D-galactose (60 mg/kg, intraperitoneally), while from day 30, MemophenolTM (15 mg/kg) was supplied orally for 30 consecutive days. AlCl3 accumulates mainly in the hippocampus, the main part of the brain involved in memory and learning. Behavioral tests were performed the day before the sacrifice when brains were collected for analysis. Results: MemophenolTM decreased behavioral alterations and hippocampus neuronal degeneration. It also lowered phosphorylated Tau (p-Tau) levels, amyloid precursor protein (APP) overexpression, and β-amyloid (Aβ) buildup. Furthermore, MemophenolTM reduced the pro-oxidative and pro-inflammatory hippocampus changes caused by AD. Our finding, relevant to AD pathogenesis and therapeutics, suggests that MemophenolTM, by modulating oxidative and inflammatory pathways and by regulating cellular brain stress response mechanisms, protects against the behavioral and histopathological changes associated with AD.
... Neutrophils participate in and aggravate the inflammatory response of AP through neutrophil NADP oxidase-induced oxidative stress and increase the activation of trypsinogen in PACs. In AP, neutrophils in peripheral blood migrate through the vascular endothelial cell space to the injured PACs, and the enhanced expression of ROS and NADPH oxidase further stimulates neutrophils to produce more pro-inflammatory cells [30,31]. However, many neutrophils lose the ability to clear the microbial infection, which can further aggravate the severity of damage at infection sites, thereby inducing a severe inflammatory response and even SIRS. ...
The inflammatory immune response mediated by neutrophils is closely related to the progression of acute pancreatitis. Previous studies confirmed that CD177 is a neutrophil-specific marker involved in the pathogenesis of conditions such as systemic vasculitis, asthma, and polycythemia vera. Neutrophil extracellular trap (NET) formation is a specific death program by which neutrophils release nuclear DNA covered with histones, granule proteins, etc. It also plays an important role in host defense and various pathological reactions. However, the function of CD177 in regulating the generation of NETs and the development of acute pancreatitis (AP) is unclear. In our manuscript, CD177 was significantly elevated in blood neutrophils in patients and positively correlated with the AP disease severity. Then, recombinant human CD177 protein (rhCD177) could significantly improve pancreatic injury and the inflammatory response in AP mice, and reduce AP-related lung injury. Mechanistically, we found that rhCD177 could inhibit the formation of NETs by reducing reactive oxygen species (ROS) and myeloperoxidase (MPO)/citrullinated histone H3 (CitH3) release. For the first time, we discovered the potential of rhCD177 to protect AP in mice and inhibit the NET formation of AP. CD177 may be a potential treatment strategy for preventing or inhibiting the aggravation of AP.
... Complex factors contribute to the stimulation of the exocrine pancreas, including the intake of highly caloric food (>500 kcal), the presence of free fatty acids in the duodenum, the intake of essential aminoacids (phenylalanine, valine, methionine, tryptophane) and solid rather than liquid or semi-liquid dietary consumption (slower gastric emptying). The exocrine stimulation mainly occurs through the vagus nerve and the secretion of cholecystokinin (CCK) [3][4][5]. ...
Pancreatic insufficiency, both acute and chronic, is an important cause of maldigestion and malnutrition caused by impaired exocrine pancreatic function. Many causes are able to determine pancreatic insufficiency which, depending on the severity, can manifest itself with very diversified symptoms. The chapter will illustrate the diagnostic and monitoring methods of pancreatic pathology in the acute and chronic phases. Great attention will be given to oral nutrition, in its various forms, including enteral and peranterior artificial nutrition. Finally, we will discuss the most appropriate pharmacological therapy to optimise food absorption in the different phases of the disease. Each of the aspects considered takes into account the most recent literature and the clinical experience of the authors.
