Nephroprotective effects of Datura stramonium leaves against methotrexate nephrotoxicity via attenuation of oxidative stress-mediated inflammation and apoptosis in rats

Objective: Methotrexate (MTX) is a frontline antimetabolite anticancer drug which is used in different cancer treatments but its nephrotoxicity is a notable drawback that limits its clinical use. The present study was undertaken to examine whether Datura stramonium leaf extract (DSLE) could block MTX nephrotoxic side effect in rats.Materials and Methods: Animals were divided randomly into Control, Ethanol extract, MTX, and Extract + MTX groups. DSLE (۲۰۰ mg/kg bw) was orally administered for ۲۱ days, while MTX was injected intraperitoneally (ip) on the ۱۸th day. Serum levels of urea, creatinine and uric acid were determined. Kidney samples were used to determine glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) activities, and renal levels of malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide (NO), interleukin-۶ (IL-۶), tumor necrosis factor-α (TNF-α) and caspase-۳.Results: Injection of MTX resulted in considerable increases (p<۰.۰۵) in creatinine, urea, and uric acid levels as well as renal MDA, NO, IL-۶, TNF-α and caspase-۳ compared to the controls. SOD and GPx increased significantly, while GSH was significantly depleted. Interestingly, DSLE markedly reduced (p<۰.۰۵) levels of creatinine, urea, uric acid, TNF-α, NO, MDA and caspase-۳, whereas renal GSH increased markedly compared to the MTX group.Conclusion: DSLE has nephroprotective activity against MTX toxicity. However, further mechanistic studies are needed.

Keywords:

Methotrexate , Inflammation , Antioxidants , Apoptosis , D. stramonium