Nephroprotective effect of Withania somnifera: a dose-dependent study.
ABSTRACT In the present study, we investigated the protective effect of Withania somnifera, an indigenous medicinal herb used in ayurvedic traditional systems for more than 3000 years in India, on gentamicin (GEN)-induced nephrotoxicity. The root extract of three different doses of W. somnifera (viz., 250, 500, and 750 mg/kg) was administered orally to rats for 14 days before GEN treatment and thereafter concurrently with GEN (100 mg/kg) for 8 days. Nephrotoxicity was evident in GEN-treated rats by significant increase in kidney weight, urea, creatinine, urinary protein, and glucose, and significant reduction in body weights and potassium, which was histopathologically confirmed by tubular necrosis. In contrast W. somnifera (500 mg/kg) significantly reversed these changes as evidenced microscopically when compared to other two doses of W. somnifera (250 and 750 mg/kg), and there were no significant changes in the levels of sodium in the experimental animals compared to control. Thus, our results suggested the nephroprotective effect of Withania somnifera, which could be by enhancing antioxidant activity with natural antioxidants and scavenging the free radicals.
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ABSTRACT: The aminoglycoside antibiotic gentamicin (GM) is still widely used against infections by Gram-positive and Gram-negative aerobic bacteria. Its therapeutic efficacy, however, is limited by renal impairment that occurs in up to 30% of treated patients. The drug may accumulate in epithelial tubular cells causing a range of effects starting with loss of the brush border in epithelial cells and ending in overt tubular necrosis, activation of apoptosis and massive proteolysis. GM also causes cell death by generation of free radicals, phospholipidosis, extracellular calcium-sensing receptor stimulation and energetic catastrophe, reduced renal blood flow and inflammation. Many drugs have been shown to either ameliorate or potentiate GM nephrotoxicity. This article aims at updating the literature that has been published in the past decade on the effects of agents that either ameliorate or augment the nephrotoxicity of this aminoglycoside. Notable among the new ameliorating procedures are gene therapy, such as intravenous cell therapy with serum amyloid A protein-programmed cells, and the use of some novel antioxidant agents and oils of natural origin. These include, for example, green tea, garlic saffron, grape seed extracts as well as sesame and oleanolic oils. Agents that may augment GM nephrotoxicity include indomethacin, cyclosporin, uric acid and the Ca(++) -channel blocker verapamil. Most of the nephroprotective agents mentioned here have not been tested in large controlled clinical trials. Because of their relative safety and effectiveness, antioxidant agents seem to be good candidates for testing in humans.Basic & Clinical Pharmacology & Toxicology 05/2011; 109(4):225-32. · 2.18 Impact Factor
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ABSTRACT: ETHNOPHARMACOLOGICAL RELEVANCE: Euclea divinorum Hierns (Ebenaceae) is used in Ethiopian folklore medicine to treat scabies, inflammation of the skin, eczema, abdominal pain, gonorrhea, and kidney problems. However, the claim has not been scientifically validated. AIM OF THE STUDY: To assess the renoprotective effects of the crude extract and solvent fractions of E. divinorum leaves against gentamicin-induced nephrotoxicity in rats. MATERIALS AND METHOD: Rats of either sex were divided into seven experimental groups, each comprising six animals. Group I served as control and given vehicle (Tween 80, 2%, v/v in water) and Group II were treated with gentamicin intraperitoneally (100mg/kg/day) for eight days. Group III-V received crude extract at three different doses 100mg/kg, 150mg/kg and 200mg/kg, respectively. Group VI received 100mg/kg of the methanolic fraction and Group VII 100mg/kg of the aqueous fraction. The extract was administered orally two days before and eight days concomitantly with gentamicin. Following treatment, blood and renal tissue were used to assess creatinine, blood urea nitrogen (BUN), malonaldehyde (MDA), antioxidant enzymes and tubular necrosis using recommended procedures. In addition, free radical scavenging activity was determined using in vitro methods. RESULTS: Gentamicin significantly increased serum creatinine and BUN, MDA and tubular necrosis in rats. It also decreased activity of catalase and superoxide dismutase as well as levels of gluthatione. Pre- and co-treatment with the crude extract and solvent fractions of E. divinorum leaves reversed gentamicin-induced alterations as evidenced by a decrease in tubular necrosis, serum and oxidant markers as well as by an increase in antioxidant molecules. Effect was found to decrease with dose when the crude extract was used and maximum protection was conferred by the 100mg/kg of the methanolic fraction in both in vivo and in vitro studies. CONCLUSIONS: E. divinorum reversed gentamicin-nduced nephrotoxicity, probably via its antioxidant activity. The fact that the methanol fraction conferred maximum protection suggests that semi polar antioxidant principles might be responsible for the observed effect.Journal of ethnopharmacology 12/2012; · 2.32 Impact Factor
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ABSTRACT: Visceral leishmaniasis (VL) or kala-azar continues to persist as one of the major public health problems in many tropical countries. However, no effective treatment for cure of the disease is yet available. The present study was designed to investigate the nephroprotective and immunomodulatory effect of Withania somnifera in cisplatin-treated Leishmania donovani-infected BALB/c mice. Administration of cisplatin (5 mg/kg body weight (b.wt.) daily for 5 days, i.p.) reduced the parasite load in L. donovani-infected BALB/c mice but produced damage in liver and kidney as manifested biochemically by an increase in SGOT, SGPT, serum creatinine, and blood urea nitrogen, respectively. The biochemical analysis was further substantiated by histopathological changes induced in the liver and kidney by cisplatin. However, W. somnifera (350 mg/kg b.wt. daily for 15 days, orally) when given along with cisplatin, significantly reversed these changes and enhanced the antileishmanial efficacy of the drug, cisplatin. But, when W. somnifera was given alone per se it showed less antileishmanial potential. The results also indicate that W. somnifera in combination with cisplatin resulted in significant selective upregulation of Th1 type of immunity because it guided expression of T helper cell (Th1)1 cytokines, IFN-gamma and IL-2; augmented levels of IgG2a over IgG1; and heightened DTH (delayed type hypersensitivity) responses while Th2 cytokines, IL-4, and IL-10 were downregulated. Flow cytometric analysis of W. somnifera and cisplatin-treated animals showed an increase in the percentage of T cells (CD4+, CD8+) and NK1.1 suggesting its effect on activation of T cells. These results confirm the protective and immunomodulatory activity of W. somnifera suggesting that it along with cisplatin may be a critical remedy for the amelioration of adverse effects of cisplatin. Thus, this combination appears to offer a fruitful strategy for treatment of VL.Parasitology Research 03/2013; · 2.85 Impact Factor