Attenuation of methotrexate-induced hepatorenal damage by Terminalia bellerica fruit extract in experimental rats

Background: Methotrexate (MTX) is used for numerous malignancies and autoimmune disorders. With such widespread use, MTX-induced hepatorenal toxicity is an issue of concern that still needs to be addressed. Objective: The aim of the present study is to evaluate the role of Terminalia bellerica extract (TBE) in MTX-induced hepatorenal toxicity in Wistar albino rats. Materials and Methods: Rats were randomly divided into six groups ( n = 6) – received MTX 20 mg/kg intraperitoneally on the 4 th day along with pretreatment with different doses of TBE (100 mg/kg, 200 mg/kg, and 400 mg/kg, p.o) given from 1 st to 15 th day. MTX-induced hepatorenal toxicity was evaluated by biochemical hepatic and renal parameters along with histopathology and immunohistochemistry. Results: Hepatorenal toxicity induced by MTX was attributed to increased oxidative stress, biochemical liver, and kidney parameters and upregulation of caspase-3 and nuclear factor kappa B (NFkB). MTX-treated group observed twofold to threefold rise in aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), and creatinine values–138.49 IU/L, 125.81 IU/L, 63.09 mg/dl, and 1.895 mg/dl, respectively. Groups pretreated with TBE (400 mg/kg) observed a significant decrease ( P Conclusion: T. bellerica fruit extract (400 mg/kg) showed significant hepatorenal protection by reducing oxidative stress, elevating serum enzymes, and downregulating the tissue expressions of caspase-3 and NFkB. Abbreviations Used: ALT: Alanine transaminase, AST: Aspartate aminotransferase, BUN: Blood urea nitrogen, TBE: Terminalia bellerica fruit extract, GSH: Glutathione, MDA: Malondialdehyde, MTX: Methotrexate, NFkB: Nuclear Factor kappa B.