Protective Effect of Withania coagulans Fruit Extract on Cisplatin-induced Nephrotoxicity in Rats.

Abstract

Background:Fruits of Withania coagulans (Solanaceae) reported to possess several bioactive compounds as curative agents for various clinical conditions. Cisplatin is a chemotherapeutic drug to treat sarcomas, carcinomas, lymphomas, cervical cancer, germ cell tumors, etc. The major factor that limits its clinical use is its dose-dependent nephrotoxicity.Aim:To explore the nephroprotective effect of W. coagulans extract and its modulatory effects against cisplatin-induced nephrotoxicity and genotoxicity.Materials and Methods:W. coagulans fruit extract was quantitatively standardized with withaferin A using high-performance thin-layer chromatography. The subacute toxicity study was performed according to OECD guidelines in experimental rats. Nephrotoxicity in rats was induced by a single dose of cisplatin (6 mg/kg, intraperitoneal). Nephroprotective role of W. coagulans fruit extract at different doses had been evaluated. It includes quantification of serum kidney toxicity markers, renal tissue oxidative stress biomarkers and pro-inflammatory cytokines level, DNA fragmentation assay, and histopathological examination of renal tissue.Results:Withaferin A was found 3.56 mg/g of W. coagulans fruit extract. It significantly prevented the rise in serum urea and creatinine level and also preserve rat kidneys from oxidative stress and free radical induced DNA damage. Histopathological study showed extract treatment eliminates tubular swelling, cellular necrosis, and protein cast deposition in cisplatin treated kidney tissue. It averted the decline in glutathione content, activities of superoxide dismutase and catalase. These parameters were restored to near normal levels by extract in a dose of 400 mg/kg, per oral. Conclusion: It can be justified that W. coagulans possess dose dependent protective effect against cisplatin induced kidney damages, primarily through its free radical scavenging and anti inflammatory activitySUMMARY Authentication and standardization of Withania coagulans fruitsSubacute oral toxicity studyEvaluation of nephroprotective activity against cisplatin-induced nephrotoxicityDNA fragmentation assay and histopathological examination of kidney tissue in experimental rats. Abbreviations Used: WHO: World Health Organization, SOD: Superoxide dismutase, CAT: Catalase, HPTLC: High-performance thin layer chromatography, p.o.: Per.oral, i.p.: Intraperitoneal, TNF-α: Tumor necrosis factor-alpha, IL-1β: Interleukin 1-beta, IL-6: Interleukin-6