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The preventive effect of N-butanol fraction of Nigella sativa on ethylene glycol-induced kidney calculi in rats
Abstract and Figures
The current study was carried out to determine whether the aqueous-ethanolic extract or the butanolic fraction of Nigella sativa (NS) seeds could prevent or reduce calculi aggregation in experimental calcium oxalate nephrolithiasis in Wistar rats.
Male Wistar rats were randomly divided into 5 groups: group A received tap drinking water for 28 days. Groups B, C, D and E received 1% ethylene glycol for induction of calcium oxalate (CaOx) calculus formation for 28 days. Rats in groups C, D and E also received aqueous-ethanolic extract of NS, N-butanol fraction and N-butanol phase remnant of NS, respectively, in drinking water at a dose of 250 mg/kg for 28 days. Urine concentration of oxalate, citrate, and calcium on days 0, 14, and 28, and also serum concentration of magnesium and calcium on days 0 and 28, were measured. On day 29, kidneys were removed for histopathologic study and examined for counting the calcium oxalate deposits in 10 microscopic fields.
Treatment of rats with N-butanol fraction and N-butanol phase remnant of NS significantly reduced the number and size of kidney calcium oxalate deposits compared with ethylene glycol group. Urinary concentration of oxalate in all experimental groups increased compared with control group on days 14 and 28, whereas the urine citrate concentration was lower in all experimental groups compared with control group on days 14 and 28.
N-butanol fraction and N-butanol phase remnant of NS showed a beneficial effect on calcium oxalate deposition in the rat kidney. Therefore, the butanolic fraction of NS may be suggested for prevention of calcium oxalate calculi in humans.
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... The active component of Nigella sativa is thymoquinone; has over 100 chemical compounds and has minerals such as Mg, calcium, phosphorus, potassium, iron, copper, zinc, manganese and vitamins A, B, C, D and E in the seeds (Ali et al., 2012;Cheikh-Rouhou et al., 2007;Houghton et al., 1995;Trejo, 2009). It is rich in both fixed and essential oils, proteins, alkaloids, saponin polyphenols and flavonoids; has great antioxidant, free radicals scavenging, analgesic, anti-inflammatory, anticonvulsant, hypoglycemic, hypocholestermic, carminative, diuretic, lactagogue, vermifuge antihypertensive, antiulcer, antidiabetic, antimicrobial, antineoplastic and anticancer activity; it also balances enzyme activity, reduced the number and size of kidney calcium oxalate; has been traditionally used as a folk medicine for more than 2000 years and has been shown to produce multi-systemic beneficial action (Ali & Blunden, 2003;Cheikh-Rouhou et al., 2007;El-Bahai et al., 2009;Hadjzadeh et al., 2011). ...
... The active component of NS is thymoquinone; has over 100 chemical compounds and has Vitamins such as Mg, calcium, potassium, iron, copper, zinc and Vitamins A, B, C, D and E in the seeds (Ali et al., 2012;Cheikh-Rouhou et al., 2007;Houghton et al., 1995;Trejo, 2009). It is rich in both fixed and essential oils, proteins, alkaloids, saponin polyphenols, flavonoids and minerals (Ali & Blunden, 2003;El-Bahai et al., 2009;Hadjzadeh et al., 2011). In the present study pre values of Mg 2+ , tMg, K + and Hb in Ex+NS group are markedly increased as compared with pre value of Ex group after administration of NS. ...
... In the present study pre values of Mg 2+ , tMg, K + and Hb in Ex+NS group are markedly increased as compared with pre value of Ex group after administration of NS. These findings may be for its nutritive quality had supported by the study of (Demir et al., 2006;Hadjzadeh et al., 2011;Meral & Kanter, 2003;Pari & Sankaranarayanan, 2009). ...
... No statistically significant change in magnesium level was reported [1]. It is known that urine calcium level increases in EG group [34], on the contrary, it was reported that calcium decreased in studies consistent with our results [35,36]. In the study, it was observed that there was a statistically significant decrease in calcium level starting from 7 days on 14 and 21 days. ...
... The blood magnesium, calcium, creatinine, uric sit and microprotein levels were evaluated, no statistically significant changes were observed. No significant changes in calcium and magnesium levels of hyperoxaluria rats have been reported [35,40]. Glomerular basement membrane (GBM) thickening and accumulation in the mesangial matrix are known in diseases, such as diabetic nephropathy. ...
The aim of this study is to investigate whether the filtration barrier is affected by experimental kidney stone formation. Thirty-two rats divided into 4 equally groups (n = 8) at random. Group I control; Group II 1% ethylene glycol; Group III 1% Ethylene glycol + 0.25% Ammonium chloride; Group IV 1% Ethylene glycol + 0.5% Ammonium chloride group. Tissues applied hematoxylin–eosin, periodic-acid-Schiff, Pizzolato's staining. Immunohistochemically stained with integrin α3β1, type IV collagen, laminin, nephrin, CD2-associated protein (CD2AP) and podocin to show the filtration barrier structure. The TUNEL method was used for apoptosis. The amount of calcium, magnesium, creatinine and uric acid in urine and blood samples, also urine microprotein determined. Stones were formed in all experimental groups. Urine calcium, creatinine, uric acid levels decreased, magnesium levels were not changed. No statistically significant change was observed in blood serum results and TUNEL analysis. Immunohistochemical results showed an increase in nephrin, podocin, CD2AP, laminin and a decrease in integrin α3β1 and type IV collagen. Consequently, there is an increase in the expression densities of the proteins incorporated in the structure to prevent loss of functionality in the cellular part supporting the structure against a weakening of the basement membrane structure in the glomerular structure in which urine is filtered.
... Oxalate crystals in renal tubules were counted in 10 microscopic fields of H&E slides of each group [17] . Similarly, the immunostained sections were examined using an Olympus DP2-BSW Image computer system (Olympus Imaging System., Tokyo, Japan), and Image-Pro Plus program (version 4.5.1.27) ...
... PAS stained sections also revealed damaged brush border and interrupted basal lamina of the renal tubules. The previous studies on ethylene glycol induced hyperoxalurea showed renal tubular dilatation with epithelial damage in rats [17] . The tubular dilatation was not profound and not affecting the majority of the tubules, in the present study ,may be due to the short period of exposure to oxalate. ...
Background: Oxalate is a frequent component in foods from plant origin. Extraordinary concentrations of oxalate in urine leads to several renal pathological disorders. Green tea and black tea have several beneficial effects attributed to their polyphenols which act as metal chelators and scavengers of free radicals. Aim: The present study aimed to clarify the possible ameliorating impact of black and green tea on renal tissue damage caused by oxalate. Material and Methods: Thirty male mice were divided into six groups: Group I (control) ,Group II were injected with sodium oxalate, group IIIwere fed with black tea extract and group IV were fed with black tea extract and injected with sodium oxalate, group V were fed with green tea extract and group VI were fed with green tea extract and injected with sodium oxalate. The black or green tea extracts were given orally for 10 days (2ml/100g/day). Sodium oxalate (100 mg/kg) were injected as a single intraperitoneal dose at the11th day and animals sacrificed 12 h later. At the end of experiment, blood samples and kidney specimenswere obtained from all groups. Serum urea and creatinine analysis were done. The renal tissue sections were stained with H&E and PAS stains and examined. Immunohistochemical investigation for iNOS and NF-κB and morphometric analysis were also implemented. Results:Microscopically, the examined kidneys in oxalate group revealed degenerated and necrotic tubular cells ,tubular dilatation, protein casts and translucent oxalate crystals and interrupted tubular brush border and basal laminae. Furthermore, serum urea and creatinine were elevated and iNOS and NF-κB immunoreaction were highly positive. The aforementioned changes were reversed in group IVand VI. Conclusion: Black and green tea extracts could protect against oxalate-induced nephrotoxicity due to their antioxidant characters.
... Reactive oxygen species are the most destructive factors of stone formation [5]. Medicinal plants with wellknown antioxidative and diuretic effects are useful for prevention of nephrolithiasis [6]. Many herbs are used to treat kidney stones, but the action of most of these herbs have not yet proved scientifically. ...
... C. dactylon has shown immunomodulatory and free radical scavenging activity, in addition to anti-inflammatory and antioxidative effect on rats [54,55]. Rad et al. [6] reported preventive effects of hydroalcoholic extract of C. dactylon roots on calcium oxalate calculi in rat treated with 1% EG daily for 28 days. C. dactylon aqueous decoction reduced stone formation against ethylene glycol (1% v/v) given in drinking water for 6 weeks on rats [56]. ...
... 90 It was shown that black seed had preventative and therapeutic effects on renal stones and renal damage. [90][91][92] A randomized controlled trial by Movaghati showed that 44.4% of patients who received black seed treatment completely excreted their stones, whereas 15.3% of patients in the placebo group achieved the same outcome. 90 Moreover, they observed a more significant reduction in renal stone size after treatment in the black seed group than in the placebo group. ...
Kidney stones refer to abnormal crystal formation that occurs in the kidney. Among a variety of components of kidney stones, calcium oxalate (CaOx) is the most common type. Despite many efforts to investigate the pathogenesis of CaOx stones, the pathogenesis remains an issue of debate. With high occurrence and recurrence, individuals with stone formation are prone to frequently consult a doctor and to be hospitalized, and the treatment of kidney stones poses a heavy burden on the patients. Concerns should be focused not only on treatment but also on prevention. Herein, we reviewed the studies on prevention methods of CaOx stones through diet, lifestyle, and medication extending until the current time frame. As hyperoxaluria is the most common metabolic disorder among CaOx stone formations, we also included several studies on the treatment and prevention of hyperoxaluria. Our objective was to outline the effective methods to prevent renal CaOx stone formation.
... The results of Tables 2 and 3 show that most of the studies were carried out on animals. In the animal model, plants showed renal protective effects [86,90,94,96], increased urine volume [84,88,89,92,101,106,115,116], reduced calcium crystals deposition [106,108,109] and as a result, reduced calcium oxalate stone formation [82,87,98,100,113], along with decreasing the excretion of potassium [101,108], urea and creatinine in the urine [101,115,117]. A decrease in the amount of creatinine, uric acid and BUN in the serum was also observed [85,94,98,104,110]. ...
Urinary stone disease is the most common urinary tract disease that has caused human suffering since ancient times. The observation of a 7000-year-old bladder stone in an Egyptian skeleton proves this claim. This disease causes many complications for patients, but its pathogenesis is unclear. The knowledge about the cause of urinary stones formation and treatment recommendations from ancient physicians' perspectives is probably helpful in preventing and treating kidney stones. Data for this review were provided by search in five Traditional Persian sources available, including Canon of Medicine (Avicenna, 980-1037 AD), Kamil al–Sana al-Tibbiya (Majusi Ahwazi (Haly Abbas), died 982-994), Zakhire Kharazmshahi (Jorjani, 1042-1137 AD), Makhzan al Adviyeh (Mohammad Hossein Aghili Khorasani Shirazi in 18th AD), and Tib-e-Akbari (Mohammad Akbar Arzani-11th and 12th centuries AD) and Until January of 2023, all English publications in Science Direct, PubMed, Google Scholar and Scopus, using various search terms such as urolithiasis, lithiasis, and kidney stone. Some dietary recommendations in Traditional Persian Medicine (TPM) for treatment of urinary tract stones and 134 recommended plant species, in addition to studies of in vivo effects of some of them in conventional medicine have been described in this article. The TPM with long experience and special principles has good potential in the field of diagnosis and treatment in its own way and can act as a strong complementary treatment system for diseases that have challenging treatment. It seems using the experiences in the TPM sources and relying on today's knowledge can create a way to prevent the formation and recurrence of urinary tract stones.
... In Persian traditional medicine, different medicinal plants have been used to remove or dissolve kidney stones or prevent their formation (17). So far, several studies have shown the positive effects of some of these medicinal plants on animal models for kidney stone formation (18). Melon (Cucumis melo L.) is a plant of the Cucurbitaceae genus (19). ...
Introduction: Both watermelon and Persian melon extracts have various pharmacological properties like anti-diabetic, anti-viral, anti-cancer, and anti-urolithiasis effects. Objectives: The present study was conducted to investigate the effects of hydroalcoholic extracts of watermelon and Persian melon rind on kidney stone prevention in male Wistar rats. Materials and Methods: Fifty-six Wister rats were randomly divided into seven groups and treated for 28 days. The first group (healthy control) and the second group (negative control) received drinking water and water containing 1% ethylene glycol, respectively. The third and fourth groups, received 100 mg/kg/d hydroalcoholic extract of watermelon rind and Persian melon rind, respectively in addition to 1% ethylene glycol. The fifth and sixth groups, received 400 mg/kg/d hydroalcoholic extract of watermelon rind and Persian melon rind, respectively in addition to 1% ethylene glycol. The seventh group received 0.5 mEq/kg/d potassium citrate in addition to 1% ethylene glycol for prevention and treatment of kidney stone. A 24-hour urine collection was conducted to determine the levels of sodium, calcium, uric acid, oxalate and citrate concentration. Histological study of calcium oxalate crystals was also performed. The serum levels of urea, creatinine, uric acid, calcium, phosphorus, magnesium, SGPT (serum glutamic-pyruvic transaminase), SGOT (serum glutamic-oxaloacetic transaminase), total antioxidant capacity, and malondialdehyde (MDA) of blood were determined accordingly. Results: In the present study, administration of high-dose extract of watermelon and Persian melon rind (400 mg/kg/d) and potassium citrate showed significant changes in variables of sodium, calcium, uric acid, citrate, urine volume ( P <0.01), blood creatinine, blood uric acid, blood calcium, and serum SGPT ( P <0.05). The histological study of calcium oxalate crystals showed a significant reduction in oxalate levels in all prevention groups. Conclusion: The extracts of watermelon and Persian melon rind are effective in preventing calcium oxalate stones by decreasing the levels of oxalate, sodium, and calcium and increasing citrate levels and urine volume and affecting the total antioxidant capacity. Persian melon rind extract was more effective than potassium citrate and watermelon rind extract in reducing urine sodium. High-dose watermelon rind extract showed similar effects as potassium citrate.
... They received care according to the criteria outlined in the Guide for the Care and Use of Laboratory Animals. 10 They were kept for acclimatisation for one week. ...
... In folklore medicine, N. sativa seeds and oil have been regularly prescribed as a natural remedy for various diseases such as fever, cough, nasal congestion, bronchitis, asthma, dyspnea, hypertension, diabetes mellitus, inflammation, eczema, dizziness, gastrointestinal problems, and pain conditions [11,12]. Furthermore, N. sativa has multiple biological and pharmacological functions including antioxidant [13][14][15], anti-inflammatory and analgesic [16,17], anticancer [18,19], antimicrobial [20,21], immune enhancement [22,23], hypoglycemic [24], hypotensive [25], hypolipidemic and cardioprotective [26][27][28], hepato-protective, gastro-protective [29,30], renal-protective [31,32], spasmolytic, bronchodilator [33][34][35], and increased milk production [36]. Moreover, N. Sativa has been beneficial for convulsion [37,38], depression [39], menʼs infertility [40], and memory improvement [41]. ...
Considering the different untoward effects of the drugs prescribed for the treatment of rheumatoid arthritis (RA), there has been an increasing interest in adjuvant therapies devoid of such unfavorable reactions. Although the beneficial effects of Nigella sativa (N. sativa) on RA have been established, it seems that its mechanisms of action have not still been reviewed. The present review is designed to evaluate the effects of N. sativa on RA systematically. We searched these electronic databases until April 2019: PubMed, Scopus, ISI Web of Science, Cochrane Library, Embase, Ovid, ProQuest, and Google scholar. No restriction was conducted based on language or publication date. We selected all of the related clinical, animal, and in vitro studies. Review papers, abstracts in conferences, book chapters, and papers regarding the effects of N. sativa combined with other herbs, as well as articles regarding the effects of N. sativa on other diseases, were excluded. Each article was assessed critically for the possible risk of bias. Nineteen articles were reviewed. Animal and in vitro investigations supported the favorable effects of N. sativa on clinical, inflammatory, oxidative, and immunologic parameters on RA, whereas results of limited clinical studies did not illustrate any change or improvement of inflammatory and oxidative biomarkers in RA. N. sativa could control RA via multiple ways such as decreasing inflammation, inhibiting oxidative stress, and modulating the immune system. This paper provides persuasive clues to defend the efficacy of N. sativa in RA and justifies the significance of subsequent clinical trials.
... Nigella sativa Ranunculaceae Seeds Antioxidant, anti-inflammatory, prevents crystal formation Animals in vivo [31] . ...
Medicinal plants have been known for ancient time and are well admired in globe as a potential source of curative compounds for the prevention of different diseases. Urolithiasis is precipitation of insoluble and less soluble salt such as Oxalate and Phosphate in urinary tract causing obstruction in urethra resulting renal colic and hematuria. The information on flora was collected from various Journals, websites and books which were additionally revised to ascertain use parts, studied model, ethno medicinal use and different mechanism of action. By analysing 36 articles of 27 journals this review accumulates information of list of 94 plants of 55 families covering 21 mechanism of action which can suppress urolithiasis with three studied model. Also, Conventionally, 20 parts of these plants are used by different modes like boiling, decoction, extract, paste, juice, powder and ash. In this article, an effort has been made to highlight on effective native flora which is used in cure of urolithiasis.
... Il a également réduit la concentration d'oxalate de calcium dans l'urine. Cette action bénéfique peut être attribuée aux activités anti-oxydantes et anti-inflammatoires de l'extrait de Nigella sativa [24,25]. ...
As part of the development of natural heritage of Morocco, an ethnobotanical study was undertaken in the Tarfaya province in order to inventory the main medicinal plants used in folk medicine to treat kidney stones. The means of study is a questionnaire distributed to 150 individuals which we considered as a representative sample of the population studied. The survey revealed that the frequency of use of medicinal plants is related to the age, sex and educational level of our respondents. The analysis of the obtained results showed that 40 plant species belonging to 27 botanical families were used in this region for the treatment of kidney stones. The most cited families were Apiaceae, Lamiaceae, Leguminosae, and Poaceae. The most cited plant species were Herniaria hirsuta, Anastatica hierochuntica, Apium graveolens, Ziziphus lotus, Allium sativum and Ranunculus muricatus. The dominant plant part used in preparations was seed. The main mode of utilization was decoction. This study showed the importance of folk medicine for the local people living in the study area. Hence, this data could be the basis for ethnopharmacological and phytochemical studies. RÉSUMÉ: Dans le cadre de la valorisation du patrimoine naturel marocain, une étude ethnobotanique a été réalisée dans la province de Tarfaya afin de répertorier les principales plantes médicinales utilisées en médecine traditionnelle pour traiter la lithiase urinaire. Le moyen d'étude est un questionnaire distribué à 150 personnes de la population locale. L'enquête a révélé que la fréquence d'utilisation des plantes médicinales est liée à l'âge, au sexe et au niveau d'éducation des enquêtés. Cette étude nous a permis de recenser 40 espèces de plantes médicinales, appartenant à 27 familles botaniques, utilisées dans cette région pour le traitement de la lithiase urinaire. Les familles les plus citées sont les Apiaceae, les Lamiaceae, les Leguminosae et les Poaceae. Les espèces végétales les plus citées sont Herniaria hirsuta, Anastatica hierochuntica, Apium graveolens, Ziziphus lotus, Allium sativum et Ranunculus muricatus. La graine constitue la partie de la plante dominante dans les préparations. La décoction est la méthode la plus utilisée. Cette étude a montré l'importance de la médecine traditionnelle pour traiter la lithiase urinaire dans la zone d'étude. Ces résultats pourraient être une base de données pour les recherches ultérieures dans les domaines de la phytochimie et de la pharmacologie. MOTS-CLEFS: Étude ethnobotanique, Plantes médicinales, lithiase urinaire, Valorisation, Maroc. Étude ethnobotanique des plantes médicinales utilisées dans le traitement de la lithiase urinaire dans la province de Tarfaya (Maroc)
... N. sativa also has been reported to reduce calculi formation in rats' kidneys. (Maryam Tehranipour and Nahid Monavar et al 2011) [5]. Researchers at the Kimmel Cancer Center at Thomas Jefferson University in Philadelphia have found that thymoquinone from an extract of N. sativa seed oil, blockedpancreatic cancer cell growth and killed the cells by enhancing the process of programmed cell death (apoptosis)acting as an HDAC inhibitor. ...
... 9,10 This herb is considered to be the next best alternative Pashanabheda by Ayurvedic practioners in India as it is widely available. [9][10][11][12][13] As the extract level work is considered to be more generalized and less specific work and we are interested to identify more specific drugs for Urolithiasis, we have carried out fractionation of the hydro alcohol extract of Aerva lanata based on its bioactivity as the fraction would be more concentrated portion containing specific group of phytochemicals and produce significant results. The results of this work shall be land mark for isolation of potent active constituents and development of lead molecules development in future. ...
Background: Aerva lanata (L) Juss. Ex. Schult. (Amaranthaceae) commonly known as Pashanabheda is used traditionally in Indian system of medicines for various diseases including urolithiasis. Objective: Screening of bioactivity guided fractions of Aerva lanata (L) for antioxidant and antiurolithiatic potency. Materials and Method: The dried hydro alcoholic extract (10%) of the whole plant was fractionated with different organic solvents like dichloromethane (fraction I), ethyl acetate (fraction II), n-butanol (fraction III). Based on preliminary phytochemical tests, only two fractions (II and III) were tested for antioxidant efficacy by DPPH Radical Scavenging assay and antiurolitiathic potentials on male Wistar albino rats by administering ethylene glycol (0.75% v/v) by oral route. Urine and blood serum were collected from all the tested animals and analyzed for the presence of calcium, oxalate, magnesium, phosphate, and BUN. Both kidneys were isolated and subjected to histopathological study. Results: Antioxidant assay has revealed that the tested fractions were equally potent as that of the standard drugs (BHT and Vitamin C). The treatment with ethyl acetate and n-butanol fractions significantly decreased the calcium, phosphate and BUN levels and increase in magnesium level in experimental rats (p<0.001). The urine analysis has also revealed significant (p<0.001) reduction in crystal size in the treated rats. Conclusion: The fractions (ethyl acetate and n-butanol) have shown significant antioxidant effect along with the Antiurolithiatic potency by reducing calculi through different pathways along with mild diuretic activity. © 2018, Association of Pharmaceutical Teachers of India. All rights reserved.
... Recently, it has been reported that establishment of disulfide bonds requires enough oxidative redox potential, it is likely that such mechanism in part plays a role in the kidney stone disease (Watson, 2014) . Medicinal plants with antioxidative properties such as Nigella sativa showed preventive effects on kidney stones (Hadjzadeh et al., 2011Hadjzadeh et al., , 2007). Furthermore, different fractions and parts of C. dactylon have been shown to be effective in the treatment of renal stones (Atmani et al., 2009;). ...
Objectives
The antioxidant capacity impairs in kidney and urinary bladder of animals with stone disease. Herbal medicine can improve the antioxidant condition of renal tissue. Cynodon dactylon (C. dactylon) is a medicinal plant with antioxidative and diuretic properties and different preparations of this plant have shown promising effects in stone disease. Assessment of the whole plant decoction to prevent kidney stone disease as well as its antioxidant effects was the aim of this paper.
Materials and Methods
Fifty male Wistar rats were randomly divided into 5 experimental groups (n=10). One group was left without treatment and four groups received ethylene glycol (1% v/v) in drinking water for 6 weeks. Three doses of Cynodon dactylon aqueous decoction (12.5, 50 and 200 mg/kg BW) were added to the drinking water of groups 3-5. Finally, water intake, 24-hour urine volume, MDA, total thiol concentration and FRAP value were measured in the serum and kidney tissues. The CaOx depositions were evaluated by hematoxylin and eosin staining.
Results
Compared to the ethylene glycol-treated group, 200 mg/kg C. dactylon, lowered stone incidents, decreased urine volume, increased FRAP/g Cr (43%) and thiol content (p<0.05) with no significant alteration of water intake, MDA decreased significantly compared to C. dactylon 12.5 (p<0.01). Kidney weight increased and body weight decreased in ethylene glycol-treated group compared to the control group (p<0.05).
Conclusion
A minimum dose of 200 mg/kg C. dactylon reduced stone formation and simultaneously increased total antioxidant power of serum and preserved MDA content and water.
... [4] The hippocampus is a portion of the brain that has a crucial role in spatial learning and memory. [15][16][17] It is demonstrated that hippocampal neurons are vulnerable to changes in glucose concentration, especially during CNS development. [18] During postnatal development in rodents, first 2 weeks after birth is a period of continued active hippocampal dentate neurogenesis corresponding to the mid-second through the mid-third trimester of human gestation. ...
Background: Diabetes in pregnancy is a common metabolic disorder associated with various adverse outcomes in the offspring including impairments in attention and memory and alterations in social behavior. Glial cells are proven to have a critical role in normal function of neurons, and alteration in their activity could contribute to disturbance in the brain function. The aim of this study was to investigate the effect of maternal diabetes on hippocampal mRNA expression and distribution pattern of glial fibrillary acidic protein (GFAP) immunoreactive glial cells in the dentate gyrus (DG) of rat neonate at postnatal day 14 (P14).
Materials and Methods: Wistar female rats were randomly allocated in control, diabetic, and insulin-treated diabetic groups. Diabetes was induced by injection of streptozotocin from 4 weeks before gestation until parturition. After delivery, the male offspring was euthanized at P14.
Results: Our results showed a significant higher level of hippocampal GFAP expression and an increase in the mean number of GFAP positive cells in the DG of diabetic group offspring (P < 0.05). We also found an insignificant up-regulation in the expression of GFAP and the mean number of positive cells in the insulin-treated diabetic group neonates as compared to control group (P > 0.05).
Conclusion: The present study revealed that diabetes during pregnancy strongly increased the glial cells production in the developing rat hippocampus.
... The seeds of N. sativa have proven to have antidiabetic, anticancer, anti-inflammatory, immunomodulatory, antioxidant, antimicrobial, analgesic, spasmolytic, bronchodilatory, and hepatoprotective properties, as well as therapeutic effects on renal, gastrointestinal, neurological, and cardiovascular disorders (Ahmad et al., 2013). Many basic and clinical studies have revealed that the extract of N. sativa seeds and its constituents could be used to suppress coughs (Boskabady et al., 2003;Mahfouz and El-Dakhakhny, 1960), dissolve kidney stones (Dollah et al., 2013a;Hadjzadeh et al., 2011), inhibit carcinogenic processes (Al-Sheddi et al., 2014;Randhawa and Alghamdi, 2011), reduce abdominal pain, cure diarrhea, and be gastro-protective (Gali-Muhtasib et al., 2006). In addition, the plant has been shown to have antimicrobial, anti-inflammatory, and antioxidant properties (Chakravarty, 1993;Landa et al., 2009;Rakhshandeh et al., 2011;Randhawa and Alghamdi, 2011;Salem, 2005). ...
... The urine oxalate level also significantly decreased in prevention group compared to ethylene glycol group and no significant difference was observed between treatment and control groups. In another set of studies, the preventive action of N-butanol and Nbutanol phase remnant fractions against renal calculi was more powerful than 50% ethanolic extract (Hadjzadeh et al., 2011). They have also tested thymoquinone, the major component of N. sativa, and indicated that intraperitoneal injection of thymoquinone for 28 days had preventive and disruptive effects on the CaOx deposits . ...
Objective:
The incidence and prevalence of kidney stone is increasing worldwide. After the first recurrence the risk of subsequent relapses is higher and the time period between relapses is shortened. Urinary stones can be severely painful and make a huge economic burden. The stone disease may increase the vulnerability of patients to other diseases such as renal failure. Medicinal herbs are rich sources of antioxidants which are increasingly consumed globally for their safety, efficacy and low price. Nigella sativa is a spice plant that is widely used for prevention and treatment of many ailments in Muslim countries and worldwide. This review aims at investigation of the effects of Nigella sativa on renal injury and stone formation.
Materials and methods:
The scientific resources including PubMed, Scopus, and Google scholar were searched using key words such as: nephrolithiasis, urolithiasis, kidney/renal stone, renal injury, renal failure, urinary retention and black seed, black cumin, Nigella sativa and thymoquinone.
Results:
N. sativa and its main component, thymoquinone showed positive effects in prevention or curing kidney stones and renal failure through various mechanism such as antioxidative, anti-inflammatory, anti-eicosanoid and immunomodulatory effects. The putative candidate in many cases has been claimed to be thymoquinone but it seems that at least in part, particularly in kidney stones, the herbal melanin plays a role which requires further investigation to prove.
Conclusion:
N. sativa and its components are beneficial in prevention and curing of renal diseases including nephrolithiasis and renal damages.
... The obtained extracts were filtered and combined, and the solvent was evaporated under reduced pressure using a rotary, which yielded a blackish-brown liquid concentrate (yield 25%) that was kept in a domestic refrigerator at 4 C. The doses of NS (250, 500 and 1000 mg/kg) were selected from described values in the literature (Hadjzadeh et al. 2007;Al-Naqeep et al. 2011;Hadjzadeh et al. 2011). The extract was emulsified in water and administered to rats using an oral gavage. ...
Context Nigella sativa L. (Ranunculaceae) (NS) is traditionally used to treat many conditions such as inflammation.
Objective This study evaluates the effects of NS seeds ethanol extract in paracetamol-induced acute nephrotoxicity in rats.
Materials and methods Forty-eight female Wistar Albino rats were divided into eight groups: I = sham; II = sham + 1000 mg/kg NS; III = sham + 140 mg/kg (N-acetyl cysteine) NAC; IV = 2 g/kg paracetamol; V = 2 g/kg paracetamol + 140 mg/kg NAC; VI, VII and VIII = 2 g/kg paracetamol + 250, 500 and 1000 mg/kg NS, respectively. Paracetamol administration (oral) was carried out 1 h after NS and NAC administrations (oral), and all animals were sacrificed 24 h later.
Results Paracetamol administration significantly increased serum urea (88.05 U/L) and creatinine (0.80 U/L) when compared with the sham group (49.80 and 0.31 U/L, respectively). However, serum urea level was reduced to 65.60, 56.00 and 54.18 U/L, with 250, 500 and 1000 mg/kg doses of the extract, respectively. Also, serum creatinine level was reduced to 0.64, 0.57 and 0.52 U/L with 250, 500 and 1000 mg/kg doses of the extract, respectively. NS administration increased superoxide dismutase and glutathione, and decreased malondialdehyde levels in the kidneys. Kidney histopathological examinations showed that NS administration antagonized paracetamol-induced kidney pathological damage.
Discussion and conclusions The results suggest NS has a significant nephroprotective activity on paracetamol-induced nephrotoxicity. It may be suggested that the antiinflammatory and antioxidant effects of NS ethanolic extract originated from different compounds of its black seeds.
... The urine oxalate level also significantly decreased in prevention group compared to ethylene glycol group and no significant difference was observed between treatment and control groups. In another set of studies, the preventive action of N-butanol and Nbutanol phase remnant fractions against renal calculi was more powerful than 50% ethanolic extract (Hadjzadeh et al., 2011). They have also tested thymoquinone, the major component of N. sativa, and indicated that intraperitoneal injection of thymoquinone for 28 days had preventive and disruptive effects on the CaOx deposits . ...
Article in Press and will be published as soon as possible.
... The main part of the plant which has therapeutic effect is the seed; it has attracted the attention of researchers, and its antidiabetic, anticancer, immunomodulator, analgesic, antimicrobial, anti-inflammatory, spasmolytic, bronchodilator, hepatoprotective, renal protective, gastro-protective, and antioxidant properties have been investigated in a number of studies. There are many basic and clinical studies which have revealed that the extracts of N. sativa seeds and its constituents could be used to suppress cough (Boskabady, Kiani, & Jandaghi, 2003;Mahfouz & El-Dakhakhny, 1960), dissolve kidney stones (Dollah, Parhizkar, & Izwan, 2013;Hadjzadeh, Rad, Rajaei, Tehranipour, & Monavar, 2011), inhibit the carcinogenic process (Al-Sheddi et al., 2014;Randhawa & Alghamdi, 2011), and ameliorate abdominal pain and diarrhoea as well as provide gastro-protective (Gali-Muhtasib, El-Najjar, & Schneider-Stock, 2006), antiatherogenic cardio-protective (Asgary et al., 2013), antimicrobial and anti-inflammatory activities (Chakravarty, 1993;Landa et al., 2009;Rakhshandeh, Vahdati-Mashhadian, & Khajekaramadini, 2011;Randhawa & Alghamdi, 2011), and antioxidant effects (Jrah-Harzallah, Ben-Hadj-Khalifa, Maloul, El-Ghali, & Mahjoub, 2013;Salem, 2005). In addition, the essential oil of N. sativa was shown to have antihelminthic (Agarwal, Kharya, & Shrivastava, 1979), antinematodal (Akhtar & Riffat, 1991), antischistosomal (Mahmoud, El-Abhar, & Saleh, 1991), antimicrobial (Aboul-Ela, El-Shaer, & Ghanem, 1996;Hanafy & Hatem, 1991), and antiviral effects (Ahmad et al., 2013). ...
Nigella sativa (N. sativa) is one of the most widely used medicinal plants. It has been used as food additive, preservative, and an herbal remedy for different diseases from ancient time. In traditional medicine, many astonishing effects such as treatment and prevention of many diseases related to the respiratory, gastrointestinal, immune, and nervous system had been mentioned for N. sativa. In the last three decades, numerous research has been done to substantiate such folk properties, identifying plant-derived natural substances, and understanding their mechanisms of action in the body. N. sativa improves the action of antioxidant enzymes (catalase, glutathione peroxidase, and glutathione-S-transferase) and acts as a free radical scavenger. As an anti-cancer agent, its modulatory activity on molecular targets, including p53, p73, PTEN, STAT3, PPAR-g, activation of caspases, and generation of ROS had been demonstrated. As an anti-inflammatory and immunomodulatory agent, it suppresses inflammatory mediators, leukotrienes, prostaglandins, and B cell-mediated immune response while it balances Th1/Th2 ratio and potentiates T cell and natural killer cell-mediated immune response. We aimed to review literature and experimental data of scientific research about the basic and clinical evidence of N. sativa and its constituents on preventive (anti-inflammatory, antioxidant, and immunomodulatory) and relieving (bronchodilatory) effects on obstructive respiratory diseases.
... They received care according to the criteria outlined in the Guide for the Care and Use of Laboratory Animals. 10 They were kept for acclimatisation for one week. ...
Kidney disease is a common health problem worldwide. Acute or chronic injuries may interfere with kidney functions, eventually resulting in irreversible kidney damage. A number of recent studies have shown that the plant-derived natural products have an extensive potential for renal protection. Thymoquinone (TQ) is an essential compound derived from Nigella Sativa (NS), which is widely applied in the Middle East as a folk medicine. Previous experiments have demonstrated that TQ has a variety of potential pharmacological effects, including anti-oxidant, antibacterial, antitumor, immunomodulatory, and neuroprotective activities. In particular, the prominent renal protective efficacy of TQ has been demonstrated in both in vivo and in vitro experiments. TQ can prevent acute kidney injuries from various xenobiotics through anti-oxidation, anti-inflammatory, and anti-apoptosis effects. In addition, TQ exhibited significant pharmacological effects on renal cell carcinoma, renal fibrosis, and urinary calculi. The essential mechanisms involve scavenging ROS and increasing anti-oxidant activity, decreasing inflammatory mediators, inducing apoptosis, and inhibiting migration and invasion. The purpose of this review is to conclude the pharmacological effects and the potential mechanisms of TQ in renal protection, shedding new light on the exploration of medicinal phyto-protective agents targeting kidneys.
Background: Urolithiasis is the major cause of morbidity, and its prevalence is increasing in the world. Siddha formulas have managed pathogenic infections for ages. Siddha practice strengthens the host's immunity and resilience to pathogens. Aim: The main aim of the present investigation is to screen the anti-urolithiatic activity of the Siddha poly herbal formulation Samsakra Chooranam through the In-silico docking technique. Materials and Methods: Binding of phytocomponents with the core amino acids (CYS 527, PRO 528, HIS 529, GLY 534, ARG 583, THR 585, ARG 586) of the targets by forming hydrogen bond will hinder the function of the target protein Tamm-Horsfall protein (PDB)-4WRN which is involved in calcium oxalate crystallization. Thereby phytocomponents which inhibit the target Tamm-Horsfall protein may act as a potential therapeutic agent for the management of urolithiasis and related symptoms. Results: A total of 12 bioactive lead compounds were retrieved from the herbs present in the siddha formulation Samsakra Chooranam. From the reported data of the herb, the phytochemicals such as Glycyrrhetic acid, Liquiritin and Limonene possess maximum of three interactions with the core active amino acid residues present on the target protein Tamm-Horsfall protein. Conclusion: From the results of the present in-silico screening, we have concluded that the phytochemicals of the siddha formulation SC display strong anti-urolithiatic activity by blocking the target enzyme and this trial drug can be recommended further for the clinical management to renal stone.
Background:
The brain development during the prenatal period is affected by various factors, including the mother's metabolic condition. It has been revealed that diabetes in pregnancy is associated with structural and functional alterations in offspring's hippocampus. Hippocampus, as a critical region with well-known roles in learning and memory consolidation, is vulnerable to changes in glucose level. This study was designed to investigate the effects of maternal diabetes during the pregnancy period and insulin therapy on the neuronal density and the volume of different subfields of the hippocampus in rat offspring at postnatal day 14 (P14).
Methods:
Wistar female rats were randomly divided into diabetics (STZ-D), diabetes treated with insulin (STZ-INS) group, and controls (CON). The animals in all groups were mated by non-diabetic male rats. Two weeks after birth, male pups from each group were sacrificed. The Cavalieri method was carried out to estimate the total volume, and the numerical density of the neurons in the hippocampus and its sub regions was measured by the optical dissector technique.
Results:
Bilateral hippocampal volume decreased in the diabetic group, mainly in the CA1, dentate gyrus (DG) and subiculum areas (P ≤ 0.05), when compared to control and insulin-treated diabetic animals. In all hippocampus sub-regions, maternal diabetes resulted in a significant decrease in the number of cells in comparison with two other groups (P ≤ 0.05 each).
Conclusion:
These data indicate that diabetes during pregnancy has a negative impact on the development of the hippocampus in the rats. These changes in the volume of hippocampal CA1, DG, and subiculum areas might be at the core of underlying neurocognitive and neurobehavioral impairments observed in the children of diabetic mothers.
Preclinical studies have shown beneficial effects of black seed (Nigella sativa L.) in the prevention and treatment of renal stones. Hence, we designed a study to evaluate the renal‐stone‐dissolving efficacy of black seed. Sixty patients with renal stones were randomly enrolled in two arms of a randomized, triple‐blind, placebo‐controlled, clinical trial. The patients were treated by black seed capsules (500 mg) or placebo two times per day for 10 weeks. Patients were assessed in terms of size of renal stones by using sonography before and after intervention. In the black seed group, 44.4% of patients excreted their stones completely, and the size of the stones remained unchanged and decreased in 3.7% and 51.8% of patients, respectively. In contrast, in the placebo group, 15.3% of the patients excreted their stones completely, 11.5% had reduction in stone size, 15.3% had increase in stone size, and 57.6% had no change in their stone size. The difference in the mean size of renal stones after the study was significant between the two groups (p < 0.05). N. sativa L., as compared with placebo, is demonstrated to have significant positive effects on disappearance or reduction of size of kidney stones.
Four new oleanane-type triterpene glycosides namely 3-O-[β-d-glucopyranosyl-(1 → 2)-β-d-glucopyranosyl-(1 → 2)-α-l-arabinopyranosyl] oleanolic acid, 3-O-[β-d-glucopyranosyl-(1 → 2)-β-d-glucopyranosyl-(1 → 2)-α-l-arabinopyranosyl]-28-O-[α-l-rhamnopyranosyl-(1 → 4)-β-d-glucopyranosyl-(1 → 6)-β-d-glucopyranosyl] oleanolic acid, 3-O-[β-d-quinovopyranosyl-(1 → 3)-α-l-rhamnopyranosyl-(1 → 2)-α-l-arabinopyranosyl]-28-O-[β-d-glucopyranosyl] oleanolic acid, 3-O-[β-d-quinovopyranosyl-(1 → 3)-α-l-rhamnopyranosyl-(1 → 2)-α-l-arabinopyranosyl]-28-O-[α-l-rhamnopyranosyl(1 → 4)-β-d-glucopyranosyl-(1 → 6)-β-d-glucopyranosyl] oleanolic acid, were isolated from methanol extract of the roots of Nigella arvensis var. involucrata along with five known oleanane-type triterpene glycosides and a steroid glucoside. Structures of the new compounds were established as by using 1D and 2D NMR techniques and mass spectrometry.
Introduction: Considering the evidence which show the effect of herbal medicine on nephrolithiasis treatment, the aim of this study was to evaluate the efficacy of ethanolic extract of Smyrnium cordifolium Boiss root on prevention of calcium oxalate nephrolithiasis in rats.
Materials & methods: Thirty-two female Wistar albino rats were randomly divided into 4 groups. Normal control received water and other three groups received ethylene glycol (EG) (1% v/v) in distilled water for 28 days. Extract was given 200 mg/kg and 400 mg/kg orally in distilled water for 28 days in groups III and IV. The urea, uric acid and creatinine were measured on 28th day. 24 hr urinary volume and oxalate were measured on day 0 and 28.
Findings: EG significantly had increased serum creatinine, urea and uric acid in comparison to the normal control. Whereas serum creatinine, urea and uric acid were reduced non-significantly in groups III and IV in comparison to EG group. Smyrnium cordifolium extract significantly increased urinary volume but decreased urine oxalate level compared to EG group (P<0.05).
Discussion & Conclusions: This study showed that Smyrnium cordifolium extract was able to reduce urine oxalate in the rat. Therefore, the beneficial action of extract on human kidney stones may be suggested. However, further studies must clarify the mechanism.
Introduction: Kidney stones are the third most common urinary tract problems after urinary tract infections and prostate pathology. Kidney stones may cause extreme pain and blockage of urine flow. They are usually treated with medications that may cause a number of side-effects. Medicinal herbs are used in different cultures as a reliable source of natural remedies.
Objectives: This study aimed to determine native medicinal plants used by traditional healers of Shiraz for the treatment of kidney stones.
Materials and Methods: The ethno-medicinal data were collected between July and September 2012 through face-to-face interview with local herbalist.
Results: A total of 18 species belonging to 19 botanical families were recorded in study area. Species with the highest frequency of mentions were Alhagi maurorum (51.58%), Tribulus terrestris (51.58%), and Nigella sativa (48.14). The most frequently used plant parts were aerial parts (38%), leaf (33%) and fruits (17%). Decoction (68%) was the most frequently prescribed method of preparation. Most of the medicinal plants recommended by Shirazian herbalists have not been investigated in animal and humane models of renal stone which provides a new area of research.
Conclusion: In the case of safety and effectiveness, they can be refined and processed to produce natural drugs.
For the first time, nucleation kinetics, crystal growth and agglomeration of calcium oxalate monohydrate are studied as crystal growth inhibitor with and without Nigella Sativa extract (NS).The induction period was determined under different supersaturation ratios ranging from 1.63 to 4.51 at 37°C using the conductivity method. Based on the classical homogeneous nucleation theory; the critical nucleation parameters were evaluated at higher supersaturation ratio. The calculated surface energy was increased from 7.97 mJ/m² without additive to 10.31 mJ/m² with Nigella Sativa extract. However, the nucleation rate at a supersaturation ratio of 3.26 corresponding to 5.44 with (NS) extract was decreased from 3.9 × 10²⁹ nuclei/cm³.s (without additive) to 1.3 × 10²⁹ nuclei/cm³.s with (NS) extract addition. The number of molecules required for the formation of stable nucleus was calculated with and without NS extract at different supersaturation ratios. The crystallite sizes of the formed crystals without and with additive are 93 and 51 nm, respectively. Scanning electron microscopy photomicrographs show the formation of small crystals and less aggregated with (NS) inhibitor compared with the baseline (without inhibitor). This study can help us to clear understanding the inhibition mechanism of an aqueous NS extract on COM crystals.
Purpose:
Citrus is considered as a medically important plant from ancient times and the bioflavonoids of different variety of citrus fruits were well explored for their biological activities. The study aim was to explore the effect of citrus bioflavonoids (CB) to prevent and cure hyperoxaluria induced urolithiasis.
Methods:
Twenty four Wistar rats were segregated into 4 Groups. Group 1: Control; Group 2: Urolithic (EG-0.75%); Group 3: Preventive study (EG+CB, day 1-50); Group 4: Curative study (EG+CB, day 30-50). Animals received CB orally (20mg/kg body weight) after performing a toxicity study.
Results:
Urinary risk factors and serum renal function parameters were significantly reduced by CB administration in both preventive and curative study (p<0.001). Hematoxylin & Eosin and von Kossa staining demonstrated that renal protection was offered by CB against EG insult. Immunohistochemical analyses revealed over expression and abnormal localization of THP and NF-κB in urolithic rats, while it was effectively regulated by CB supplementation.
Conclusion:
CB prevented and significantly controlled lithogenic factors and CaOx deposition in rats. We propose CB as a potential therapy in management of urolithiasis.
The results of phytochemical studies of 422 plants (879 specimens) of 56 families obtained from the Khorasan province of Iran are presented in this paper. The qualtitative chemical analysis was done to determine presence of alkaloids, flavonoids, saponins, and tannins.
The whole-plant, Pergularia daemia (Family: Asclepediaceae), extract (50% alcohol) was investigated for its
antiurolithiatic and diuretic activity. Ethylene glycol (0.75% in water) feeding resulted in hyperoxaluria as well
as increased renal excretion of calcium and phosphate. Alcoholic extract (400 mg/kg) of P. daemia was given
orally in curative and preventive regimens over a period of 28 days. Supplementation with extract significantly
(P < 0.001) lowered the urinary excretion and kidney retention levels of oxalate, calcium and phosphate.
Furthermore, high serum levels of urea nitrogen, creatinine and uric acid were significantly (P < 0.001) reduced by the extract. The results were comparable with the standard drug, cystone (750 mg/kg). The reduction of stoneforming
constituents in urine and their decreased kidney retention reduces the solubility product of crystallizing
salts such as calcium oxalate and calcium phosphate, which could contribute to the antiurolithiatic property of the extract. The extract exhibited significant diuretic activity at dose of 400 mg/kg body weight as evidenced by increased total urine volume and the urine concentration of Na+, and K+. These findings affirm assertions made regarding the effectiveness of the extract of this plant against urinary pathologies in the Indian folk medicine.
Renal epithelial cell injury by reactive oxygen species is pre-requisite step in the pathogenesis of urolithiasis. Rutin and curcumin are polyphenolic compounds known to have antioxidant and anti-inflammatory activities, but their effect on urolithiasis is yet to be elucidated. In the present study, we have investigated the inhibitory effect of rutin and curcumin on calcium oxalate urolithiasis in Wistar albino rats.
Calcium oxalate urolithiasis was induced experimentally by administration of 0.75% v/v ethylene glycol with 1% w/v ammonium chloride in drinking water for three days followed by only 0.75% v/v ethylene glycol for 25 days. Rutin (20 mg/kg body weight) and curcumin (60 mg/kg body weight) were given once daily for 28 days by oral route. After treatment period, calcium and oxalate levels in urine and kidney tissue homogenate were measured. Kidney was also used for histopathological examination.
Stone-induction with ethylene glycol and ammonium chloride resulted in elevated levels of calcium and oxalate in the urine and kidney sample, whereas supplementation of rutin and curcumin restored it near to normal. Histopathological study revealed minimum tissue damage and less number of calcium oxalate deposits in kidney of animal treated with rutin and curcumin as compared to calculi-induced animal.
The data suggest that the rutin and curcumin inhibits calcium oxalate urolithiasis. This effect is mediated possibly through a lowering of urinary concentration of stone forming constituents, anti-inflammatory and antioxidant effects.
The aim of this study was to investigate the effects of thymoquinone, a major component of Nigella Sativa seeds on ethylene glycol-induced kidney calculi in rats.
Sixty male Wistar rats were randomly divided into 6 groups (intact control, ethylene glycol control, and 4 experimental groups) and treated for 28 days according to the protocol of the study. The rats in experimental groups received ethylene glycol and intraperitoneal injection of thymoquinone either from the first day of the study or the 15th day, with either doses of 5 mg/kg or 10 mg/kg. Blood and 24-hour urine samples were collected at baseline and on day 28. Urine oxalate and citrate and serum electrolytes were also measured. On day 29, all rats were decapitated and their kidney specimens were studied.
On day 28, urine oxalate concentration significantly decreased in the experimental groups compared to the ethylene glycol group (P < .001). Also, serum calcium levels were significantly higher in the experimental groups (P = .001). Calcium oxalate deposits were smaller in the experimental groups than the ethylene glycol group. The mean number of deposits was lower in these groups, too (P < .001). Treatment with the lower dose of thymoquinone was associated with fewer deposits.
Thymoquinone significantly decreased the number and size of calcium oxalate deposits in the renal tubules. The dose and duration of treatment, however, does not have a linear relation with the outcomes. Further studies on thymoquinone as a preventive and therapeutic drug for kidney calculi are suggested.
This study was conducted to determine the epidemiological profile of urolithiasis in Kuwaiti patients and the associated metabolic abnormalities favouring stone formation in this patient population. Between 1986 and 1994, a total of 421 Kuwaiti patients were studied in Al-Amiri renal stone laboratory. The mineral composition of stones was determined using a combination of stereoscopic microscopy and infrared spectrophotometry. Mineral metabolic screen (MMS) was available in 306 (72.7%) of those patients. The average annual incidence of new stone formation in Kuwaiti patients was 23.9 per 100,000 population. The incidence was only 6.9 per 100,000 population in those from pediatric age group, 33.4 in adults and 73.6 in the elderly. The frequency of new stone formation was higher among males as compared to females at different age groups. Calcium oxalate (CaO) constituted 72.1% of renal stones encountered in adults as compared to only 52.1% and 40.7% in elderly and pediatric age groups. Eighty four patients had recurrent and/or high stone load. Detailed family history was available in 57 of those 84 patients and was suggestive of strong family aggregation of stone disease in 30 (53%) patients. The proportion of urate stones was 15.4% of all stones formed and constituted a major cause of renal stones in children (24.1%), adults (14.4%) and elderly (12.5%). Cystine stones were found in 10 patients (2.4%). Hyperuricemia was detected in 1/3 of patients from pediatric age group. In adults, 89 (38.4%) of 232 patients had abnormal MMS, of which hyperuricosuria with or without hyperuricemia accounted for 79.8% of those abnormalities. In elderly patients, metabolic disorders were detected in 7 (17.5%) of the 40 patients. In the latter group, all except one, had hyperuricosuria with or without hyperuricemia. Cystinuria, distal renal tubular acidosis (d-RTA) and hyperparathyroidism constituted 6.6% of metabolic abnormalities in the patients studied. Primary abnormalities of upper and lower urinary tract was detected in 6% of adult patients as compared to 47% in children and 30% in the elderly. In conclusion; the incidence rate of new stone former in Kuwait is significantly lower from that reported in Europe and USA. This latter finding and the high familial aggregation of urolithiasis in our area constitute a cogent argument against the role of hot climate in the pathogensis of urolithiasis and are in favour of genetic predisposition. Isolated hyperuricosuria was detected in 17% of idiopathic CaO stone formers. The latter finding is of practical importance since red-meat is a common food item in our area and restriction of purine-intake may help to decrease the frequency of urate and CaO stone formation in predisposed patients.
The overall probability of forming stones differs in various parts of the world: 1-5% in Asia, 5-9% in Europe, 13% in North America, 20% in Saudi Arabia. The composition of stones and their location in the urinary tract, bladder or kidneys may also significantly differ in different countries. Moreover, in the same region, the clinical and metabolic patterns of stone disease can change over time. We examined some epidemiological evidence about the main risk factors for stone formation, both individual and environmental. A slightly higher rate of renal stone disease emerged in males than in females, and in white Caucasians than in Blacks. Stones in the upper urinary tract appear to be related to the life-style, being more frequent among affluent people, living in developed countries, with high animal protein consumption. Bladder stones are nowadays mainly seen in the Third World, on account of very poor socio-economic conditions. A high frequency of stone formation among hypertensive patients has been reported, and among those with high body mass as well. There is no evidence of any rise in the risk of stone formation in relation to dietary calcium intake or tap water hardness.
The aqueous extract of Nigella sativa (N. sativa) was investigated for anti-inflammatory, analgesic and antipyretic activities in animal models. The extract has an anti-inflammatory effect demonstrated by its inhibitory effects on Carrageenan induced paw edema. It also produced significant increase in the hot plate reaction time in mice indicating analgesic effect. However, N. sativa crude suspension had no effect on yeast induced pyrexia. This study therefore, supports its use in folk medicine both as analgesic and anti-inflammatory agent and calls for further investigations to elucidate its mechanism of action.
The anticonvulsant effects of thymoquinone, the major constituent of Nigella sativa seeds, were investigated using pentylenetetrazole (PTZ)- and maximal electroshock (MES)-induced seizure models. We also studied the effect of thymoquinone on pentobarbital-induced hypnosis, locomotor activity, and motor coordination. In PTZ-induced seizure, the intraperitoneally injection of thymoquinone with doses of 40 and 80 mg/kg, prolonged the onset of seizures and reduced the duration of myoclonic seizures. The protective effect of thymoquinone against mortality was 71.4% and 100% in the mentioned doses, respectively. In MES model, thymoquinone failed to reduce the duration of seizure, whereas exhibited a complete protection against mortality. In PTZ model, flumazenil (10 mg/kg, i.p.), an antagonist of benzodiazepine (BZD) site in the GABAA-BZD receptor complex, inhibited the prolongation of seizure latency, but did not show any effect on the duration of myoclonic seizures. Also, pretreatment with naloxone (0.1 and 03 mg/kg, i.p.) inhibited the prolongation of myoclonic seizure latency and antagonized the reduction of myoclonic seizure duration induced by thymoquinone (40 and 80 mg/kg) in the PTZ model. Moreover, thymoquinone (40 and 80 mg/kg) did not have any hypnosis effect in the pentobarbital-induced hypnosis, but impaired the motor coordination and reduced the locomotor activity. These results indicate that thymoquinone may have anticonvulsant activity in the petit mal epilepsy probably through an opioid receptor-mediated increase in GABAergic tone.
Despite considerable progress in medical therapy, there is no satisfactory drug to treat kidney stones. Therefore, this current study is aimed to look for an alternative treatment by using Herniaria hirsuta on nephrolithiasic rats as a preventive agent against the development of kidney stones. The experiment was conducted in normal and calcium oxalate (CaOx) nephrolithiasic rats during 3 weeks. Several parameters were followed weekly including water intake, urinary volume and pH, some urinary chemistries, and crystalluria. At the end, kidneys were analyzed by light microscope. The results showed that water intake and urinary volume increased in nephrolithiasic rats, but their urinary pH decreased especially in the third week of treatment. Urinary oxalate increased significantly during the second week for untreated rats and remained constant in rats treated with Herniaria decoction. However, urinary calcium decreased significantly in week 2 in untreated rats and remained constant in treated rats. Qualitative analysis of crystalluria showed that untreated rats excreted large CaOx monohydrate and few dihydrate crystals while treated animals excreted mostly small CaOx dihydrate crystals. The examination of kidney sections revealed that CaOx deposition was limited in treated rats when compared to untreated ones. These results obtained in vivo confirmed the beneficial effect of Herniaria hirsuta and may justify its use as a preventive agent against the formation of calcium oxalate kidney stones.
Recently we investigated some neuropharmacological aspects of thymoquinone, such as anticonvulsant, muscle relaxant, and hypnotic effects, as well as its effect on motor coordination and locomotor activity. In this study, we evaluated the effect and mechanism(s) of the action of thymoquinone more precisely via intracerebroventricular (i.c.v.) injection.
The anticonvulsant effects of thymoquinone, the major constituent of Nigella sativa seeds, were investigated using the pentylenetetrazole (PTZ)-induced seizure model. The animals were placed individually in plastic boxes and observed immediately after PTZ injection for a period of 30 min. The latency to and the duration of tonic-clonic seizures were recorded, as well as the percentages of protection against the incidence of seizure and mortality.
In PTZ-induced epileptic seizures, the i.c.v. injection of thymoquinone at doses of 200 and 400 microM prolonged the time until onset and reduced the duration of tonic-clonic seizures. The protective effect of thymoquinone against lethality was 45% and 50% in the respective doses. In this study, flumazenil (1 nM, i.c.v.) reversed the anticonvulsant activity of thymoquinone. Also, pretreatment with naloxone (10 microM, i.c.v.) antagonized the prolongation of tonic-clonic seizure latency as well as the reduction in seizure duration induced by thymoquinone (200 microM, i.c.v.).
These results indicate that thymoquinone may have anticonvulsant activity, probably through an opioid receptor-mediated increase in GABAergic tone.
From 70% ethanol extract of the roots of Smilax bockii warb., seven flavonoids, kaempferol (1), kaempferol-7-O-beta-D-glucopyranoside (2), quercetin (3), isorhamnetin (4), (+)-dihydro-kaempferol (5), engeletin (6), isoengeletin (7), and n-butyl-beta-D-fructopyranoside (8), caffeic acid n-butyl ester (9) were isolated and identified by means of chemical and spectroscopic. Compounds 2, 4, and 6-9 were isolated for the first time from the roots of S. bockii and compounds 2, 8, and 9 were firstly isolated from the genus Smilax. In addition, using the SEAP (Secreted alkaline phosphatase) assay system, we investigated the in vitro anti-inflammatory activity of the 70% ethanol extract of the roots of S. bockii, which showed moderate activity in inhibiting TNF-alpha-induced NF-kappaB activation with an IC50 value of 166.6 microg/mL.
About 5% of American women and 12% of men will develop a kidney stone at some time in their life, and prevalence has been rising in both sexes. Approximately 80% of stones are composed of calcium oxalate (CaOx) and calcium phosphate (CaP); 10% of struvite (magnesium ammonium phosphate produced during infection with bacteria that possess the enzyme urease), 9% of uric acid (UA); and the remaining 1% are composed of cystine or ammonium acid urate or are diagnosed as drug-related stones. Stones ultimately arise because of an unwanted phase change of these substances from liquid to solid state. Here we focus on the mechanisms of pathogenesis involved in CaOx, CaP, UA, and cystine stone formation, including recent developments in our understanding of related changes in human kidney tissue and of underlying genetic causes, in addition to current therapeutics.
The flavonoids comprise a large class of low-molecular-weight plant metabolites ubiquitously distributed in food plants. These dietary antioxidants exert significant antitumor, antiallergic, and anti-inflammatory effects. The molecular mechanisms of their biological effects remain to be clearly understood. We investigated the anti-inflammatory potentials of a safe, common dietary flavonoid component, quercetin, for its ability to modulate the production and gene expression of the proinflammatory cytokine tumor necrosis factor alpha (TNF-alpha) by human peripheral blood mononuclear cells (PBMC). Our results showed that quercetin significantly inhibited TNF-alpha production and gene expression in a dose-dependent manner. Our results provide direct evidence of the anti-inflammatory effects of quercetin by PBMC, which are mediated by the inhibition of the proinflammatory cytokine TNF-alpha via modulation of NF-kappabeta1 and Ikappabeta.
The aim of this study was to investigate the effects of the ethanolic extract of Nigella sativa L (NS) seeds on kidney calculi in rats.
Thirty-two Wistar rats were randomly divided into 4 groups: group A received tap drinking water for 30 days (intact control). Groups B, C, and D received 1% ethylen glycol for induction of calcium oxalate calculus formation. As the preventive, and treatment subjects, rats in groups C and D received ethanolic extract of NS, 250 mg/kg, in drinking water since day 0 and day 14, respectively. Urine was collected on days 0, 7, 14, and 30 of the study period. After 30 days, the kidneys were removed and prepared for histologic evaluation of calcium oxalate deposits. Urine calcium oxalate concentrations were determined by atomic absorption.
The number of CaOx deposits was significantly greater in group B (P = .001). Calcium oxalate concentrations in the urine on days 14 and 30 increased significantly in group B and were higher than those in group C (P = .006 and P = .002, respectively). Urine oxalate concentration in group D decreased on day 30 and was lower than that in group B (P = .04).
Treatment of rats with ethanolic extract of NS reduced the number of calcium oxalate deposits in a group of rats that received ethanolic extract of NS. The NS could also lower the urine concentration of calcium oxalate. We suggest further studies on the therapeutic and preventive effects of the NS on kidney calculus formation in human.
Renal stones are common and its prevalence has been rising in both sexes. Treatment of patients with kidney stones in primary stages can reduce the side effects and may also prevent the surgical operations and postoperative complications. Several effects including: anti-microbial, anti-diabetic and cardioprotective effects have been reported for Cynodon dactylon. The aim of this study was to investigate the effects of N-butanol fractionand N-butanol phase remnant of Cynodon dactylon extracton calcium oxalate kidney stones in male rats.
Twenty four male Wistar rats were randomly divided into four groups. All groups were studied during 35 days of experiment according to the protocol of study. Normal control group (1) received tap drinking water. Negative control group (2) received 1% ethylene glycol in drinking water. Experimental groups (3 and 4) were treated with 1% ethylene glycol as well as 5mg/kg N-butanol fraction or 5mg/kg N-butanol phase remnant from 50% aqueous-ethanolic extract of Cynodon dactylon from first day of the experiment and continued during all protocol time.At the end of experiment, kidneys were removed for histopathologic study and examined for counting calcium oxalate deposits in 10 microscopic fields. Data were expressed as Mean± SEM and were analyzed by Kruskal-Wallis and subsequently by Mann-Whitney; p< 0.05 was considered significant. The results showed that the number of calcium oxalate deposits in 10 microscopic fields in groups 3 (p=0.008) and 4 (p=0.00) vs group 2 were significantly decreased. The results of this study revealed that N-butanol fraction and N-butanol phase remnant from 50% aqueous-ethanolic extract of Cynodon dactylon can reduce calcium oxalate stones in the rat kidney by 40 and 55% respectively. Therefore, Cynodon dactylon has beneficial effects on kidney stone removal and might be used in human treatment.
Hyperoxaluria is the foremost initiating cause for urolithiasis in renal cavities, where urolithiasis is a common urinary tract disorder. There is much expectation of finding active anti-urolithiatic compounds from indigenous plant as there are still uses in therapeutic despite the progress in conventional chemistry and pharmacology in producing effecting drugs. Most patients still have to undergo surgery to get rid of painful disease. In our present study on anti-urolithiatic agents from plants which was compared with synthetic chemical substance. As we have selected the sequential extracts of Tribulus terrestris with pet ether, chloroform, alcohol and water and compared the activity with the synthetic steroidal drug spironolactone which was used on the lithiatic induced rats and estimated the effect of the extract by doing the invo and invitro analysis alongside by histopathological studies and found the ethanolic extract of the drug was found to be effective than other treatment.
Kidney stones lead to chronic kidney disease (CKD) in people with rare hereditary disorders (e.g., primary hyperoxaluria, cystinuria), but it is unknown whether kidney stones are an important risk factor for CKD in the general population.
Among Olmsted County, MN, residents, all stone formers (n = 4774) whose condition was diagnosed in 1986 through 2003 were matched 1:3 to control subjects (n = 12,975). Cox proportional hazards models adjusted for age, gender, and comorbidities (hypertension, diabetes, obesity, dyslipidemia, gout, alcohol abuse, tobacco use, coronary artery disease, heart failure, cerebral infarct, and peripheral vascular disease) were used to assess the risk for incident CKD defined as a clinical diagnosis (diagnostic codes), ESRD or death with CKD, sustained (>90 d) elevated serum creatinine (>1.3 mg/dl in men, >1.1 mg/dl in women), or sustained estimated GFR <60 ml/min per 1.73 m(2).
During a mean of 8.6 yr of follow-up, stone formers were at increased risk for a clinical diagnosis of CKD, but an increased risk for ESRD or death with CKD was NS. Among patients with follow-up serum creatinine levels, stone formers were at increased risk for a sustained elevated serum creatinine and a sustained reduced GFR.
Kidney stones are a risk factor for CKD, and studies are warranted to assess screening and preventive measures for CKD in stone formers.
Samples of the expressed fixed oil from different sources of Nigella sativa seeds were examined by thin-layer and gas chromatography for content of fixed oils and thymoquinone, and these substances were tested as possible inhibitors of eicosanoid generation and membrane lipid peroxidation. The crude fixed oil and pure thymoquinone both inhibited the cyclooxygenase and 5-lipoxygenase pathways of arachidonate metabolism in rat peritoneal leukocytes stimulated with calcium ionophore A23187, as shown by dose-dependent inhibition of thromboxane B2 and leukotriene B4, respectively. Thymoquinone was very potent, with approximate IC50 values against 5-lipoxygenase and cyclo-oxygenase of < 1 microgram/ml and 3.5 micrograms/ml, respectively. Both substances also inhibited non-enzymatic peroxidation in ox brain phospholipid liposomes, but thymoquinone was about ten times more potent. However, the inhibition of eicosanoid generation and lipid peroxidation by the fixed oil of N. sativa is greater than is expected from its content of thymoquinone (ca. 0.2% w/v), and it is possible that other components such as the unusual C20:2 unsaturated fatty acids may contribute also to its anti-eicosanoid and antioxidant activity. These pharmacological properties of the oil support the traditional use of N. sativa and its derived products as a treatment for rheumatism and related inflammatory diseases.
The effect of thymoquinone (TQ), the main constituent of the volatile oil of Nigella sativa seeds, on the nephropathy and oxidative stress induced by doxorubicin (DOX) in rats was investigated. A single intravenous injection of DOX (6 mg/kg) induced a severe nephrotic syndrome (after 5 weeks) associated with hypoalbuminemia, hypoproteinemia, elevated serum urea, hyperlipidemia, and a high urinary excretion of protein, albumin and N-acetyl-beta-D-glucosaminidase (NAG). In the kidney, DOX induced a significant increase in total triglycerides (TG), total cholesterol (TC), and lipid peroxides and a significant decrease in non-protein sulfhydryl (NPSH) content and catalase (CAT) activity. Treatment of rats with TQ (10 mg/kg per day) supplemented with the drinking water for 5 days before DOX, and daily thereafter, significantly lowered serum urea, TG, and TC. Similarly, TG, TC and lipid peroxides in the kidneys of TQ-treated rats were decreased significantly compared with DOX alone. Moreover, NPSH content and CAT activity in the kidneys of TQ-treated DOX group were significantly elevated compared with DOX alone. Treatment with TQ significantly suppressed DOX-induced proteinuria, albuminuria, and urinary excretion of NAG. The results confirm the involvement of free radicals in the pathogenesis of nephropathy induced by DOX. Likewise, the study demonstrates the high antioxidant potential of TQ and its marked effect on the suppression of DOX-induced nephropathy. The data suggest that TQ might be applicable as a protective agent for proteinuria and hyperlipidemia associated with nephrotic syndrome.
We studied the relationship of stone frequency and composition to age, sex and stone weight.
A retrospective study was performed of all 15,624 stones submitted for analysis with infrared and wet chemical methods in Newfoundland and Labrador from 1979 to 1998.
There were 1,067 bladder stones of which 216 contained magnesium ammonium phosphate. The remaining 14,557 stones were from the kidney and ureter, and 11,707 were composed only of calcium oxalate and/or phosphate. Of the remaining 2,850 kidney and ureter stones magnesium ammonium phosphate was present in 573, uric acid/urate without magnesium ammonium phosphate in 1,109 and other compounds in 1,168. The 11,707 oxalate phosphate group was subdivided by infrared peak analysis based on oxalate-to-phosphate ratio into phosphate-ratio 1 or less, intermediate-1 to 10 and oxalate-10+. Oxalate comprised 65% of the 11,707 stones compared to 16% for phosphate. Women submitted 52% of phosphate stones compared with 28% of oxalate stones. From the first (1980 to 1983) to the last (1995 to 1998) complete 4-year study periods, there was a relative increase in oxalate and decrease in phosphate stones, associated with increasing age from decades 5 to 6 for oxalate and phosphate stones, except that the age peak for phosphate stones in women remained in decade 3. Median weight of 1, 828 phosphate stones was 43 mg. (mean 234) compared with 25 mg. (mean 98) for 7,634 oxalate stones. Male-to-female ratio was 0.91 for phosphate stones compared with 2.62 for oxalate stones.
Phosphate stones were on average heavier and relatively more common in women, had an earlier age peak frequency in women than oxalate stones and became less frequent during our last 4-year study period. In contrast, oxalate stones were much more common, of lighter weight and became more frequent with time.
The essential oil of black cumin seeds, Nigella sativa L., was tested for a possible antioxidant activity. A rapid evaluation for antioxidants, using two TLC screening methods, showed that thymoquinone and the components carvacrol, t-anethole and 4-terpineol demonstrated respectable radical scavenging property. These four constituents and the essential oil possessed variable antioxidant activity when tested in the diphenylpicrylhydracyl assay for non-specific hydrogen atom or electron donating activity. They were also effective.OH radical scavenging agents in the assay for non-enzymatic lipid peroxidation in liposomes and the deoxyribose degradation assay. GC-MS analysis of the essential oil obtained from six different samples of Nigella sativa seeds and from a commercial fixed oil showed that the qualitative composition of the volatile compounds was almost identical. Differences were mainly restricted to the quantitative composition.
Formation of calcium oxalate (CaOx) kidney stones was investigated using three approaches.
Pathogenesis of crystalluria and crystal deposition in the kidneys was examined in vivo by inducing hyperoxaluria in rats. Cultures of LLC-PK1 and MDCK cells were exposed to oxalate (Ox) and CaOx crystals to examine the effect on cells in various sections of the renal tubules. The nucleation potential of various substrates was examined by incubating them in metastable solutions of CaOx.
Calcium oxalate crystals and nonphysiologic levels of Ox were injurious to renal epithelial cells. To combat these nephrotoxins, renal epithelial cells produce a variety of macromolecules such as bikunin and osteopontin, which are modulators of crystallization and may also be involved in crystal attachment to the cells. Sustained hyperoxaluria in association with CaOx crystals induced apoptosis as well as necrosis. Cellular degradation products induced heterogeneous nucleation of crystals at lower and physiologic levels of oxalate. They also promoted aggregation.
Crystals begin to form in earlier segments of the nephron with a chance to grow and be retained in the collecting ducts after aggregation with other large crystals. Crystal deposits in the collecting ducts near the papillary surface, when exposed to the renal pelvic urine, become nidi for the development of kidney stones.
The inhibitory effect of the root of Cyclea peltata Lam. on nephrolithiasis induced in rats by feeding with ethylene glycolated water (1%) for 35 days was summarized. Ethylene glycol administration led to oxalate stone formation, as indicated by its high level in urine. Complementary to this anion, the cation calcium level in urine was elevated. These two ions may have contributed to the formation of calcium oxalate stones. In addition to high serum potassium, a low serum magnesium level contributed to stone formation. Simultaneous administration of the powdered root of Cyclea peltata resulted in decreased urinary oxalate and calcium. Likewise, serum potassium was lowered and magnesium was elevated. These observations provided the basis for the conclusion that this plant inhibits the stone formation induced by ethylene glycol treatment.
A plant mixture containing extracts of Nigella sativa possesses blood glucose lowering effects, but the direct antidiabetic effect of Nigella sativa is not yet established. Therefore, the effect of Nigella sativa oil (NSO) on blood glucose concentrations was studied in streptozotocin diabetic rats. In addition, the effect of NSO, nigellone and thymoquinone were studied on insulin secretion of isolated rat pancreatic islets in the presence of 3, 5.6 or 11.1 mM glucose. NSO significantly lowered blood glucose concentrations in diabetic rats after 2, 4 and 6 weeks. The blood lowering effect of NSO was, however, not paralleled by a stimulation of insulin release in the presence of NSO, nigellone or thymoquinone. The data indicate that the hypoglycemic effect of NSO may be mediated by extrapancreatic actions rather than by stimulated insulin release.
In the present study, Nigella sativa oil (NSO), nigellone (polythymoquinone) and derived thymoquinone were studied to evaluate their effect on the formation of 5-lipoxygenase (5-LO) products from polymorphonuclear leukocytes (PMNL).NSO produced a concentration dependent inhibition of 5-LO products and 5-hydroxy-eicosa-tetra-enoic acid (5-HETE) production with half maximal effects (IC(50)) at 25+/-1 micro g/ml, respectively 24+/-1 micro g/ml. Nigellone caused a concentration-related inhibition of 5-HETE production (IC(50): 11.9+/-0.3 micro g/ml). Moreover thymoquinone, the active principle of NSO inhibited the production of 5-LO products (IC(50): 0.26+/-0.02 micro g/ml) and 5-HETE production (IC(50): 0.36+/-0.02 micro g/ml) in a similar way. The effects are probably due to an antioxidative action. The data may in part explain the effect of the oil, its derived thymoquinone and nigellone in ameliorating inflammatory diseases.
Opuntia dillenii (Ker-Gawl) Haw. (Family Cactaceae), is used in folk medicine as an antidiabetic and antiinflammatory. The antiinflammatory activity of the alcohol extracts of the flowers, fruits and stems was carried out using the carrageenan-induced rat paw oedema model. The analgesic effect of the same extracts was evaluated using electric current as a noxious stimulus. The alcohol extract of the flowers revealed the most potent antiinflammatory effect and a pronounced analgesic action at a dose of 200 mg/kg. Bioassay-guided fractionation of this extract using VLC followed by Sephadex and paper chromatography, afforded three flavonoid glycosides, namely, kaempferol 3-O-alpha-arabinoside, isorhamnetin-3-O-glucoside and isorhamnetin-3-O-rutinoside. Their identification was based on physical, chemical and spectroscopic data.
Flavonoids possess several biological/pharmacological activities including anticancer, antimicrobial, antiviral, anti-inflammatory, immunomodulatory and antioxidant. The aim of this study was to evaluate the effect of flavonoids on macrophage physiology. For this purpose we selected some flavonoids belonging to the most common and abundant groups (flavonols--quercetin and kaempferol; flavones--diosmetin, apigenin, chrysin and luteolin; isoflavones--genistein and daidzein and flavanones--hesperetin). We decided to use primary bone marrow-derived macrophages (BMDM) as cellular model, since they represent a homogenous, non-transformed population of macrophages that can be stimulated in vitro to proliferate by macrophage colony-stimulating factor (M-CSF) or activated by LPS. In this regard, we demonstrated that most of the flavonoids assayed reduce macrophage M-CSF-induced proliferation without affecting cellular viability. Moreover, some flavonoids also inhibit TNFalpha production as well as iNOS expression and NO production in LPS-activated macrophages, an effect that has been associated with the inhibition of the NF-kappaB pathway. We also found that luteolin and quercetin are able to stimulate the expression of the anti-inflammatory cytokine IL-10 at low concentrations (<50microM). Analysis of the structure-activity relationship showed that four hydroxylations at positions 5, 7, 3' and 4', together with the double bond at C(2)-C(3) and the position of the B ring at 2, seem to be necessary for the highest anti-inflammatory effect.
Nephrolithiasis is a common disorder that accounts for significant cost, morbidity, and loss of work. There is a one in eight lifetime chance of being diagnosed with urinary stones. Calcium is the most common component of renal stones in individuals in industrialized nations. Calcium stones form as a result of a variety of environmental and metabolic abnormalities that change the urinary environment and increase supersaturation of stone-forming salts. Understanding the pathophysiology of stone disease can help direct treatment toward correction of the underlying abnormalities. Current medical and dietary therapeutic regimens have been shown to significantly reduce the risk of recurrent stone formation.
Recent reports suggest that kidney stone disease prevalence is increasing. Despite significant treatment advances, the inciting factor and sequence of events leading to kidney stone formation remain elusive; however, recent efforts to understand the pathogenesis of nephrolithiasis have led to a delineation of the human surgical anatomy, histopathology, and metabolic factors in a variety of kidney stone formers. This article reviews the fundamental concepts of calculus formation, and the leading theories of stone pathogenesis, focusing on recent data from human papillary and renal cortical biopsies in stone formers that provide evidence for the role of Randall's plaque in kidney stone disease pathogenesis. These data suggest there are individual stone-forming phenotypes with unique surgical anatomy, histology, and metabolic profiles.
Non-Calculus signs and symptoms of Hyperoxaluria and Hyperuricosuria in children: A single experience
- AD Rule
- EJ Bergstralh
- LJ Melton
- X Li
- AL Weaver
- JC Lieske
Estimation of serum lipids in albino rats fed on atherogenic supplemented palm oil diet and Nigella sativa
- A Sattar
- MS Zaman-Latif
- M Tayyib