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    Article

    Attenuation of Methotrexate‑induced Hepatorenal Damage by Terminalia bellerica Fruit Extract in Experimental Rats

    Prerna Chauhan1, Himanshu Sharma1, Surender Singh1★, Yogendra Kumar Gupta1, Uma Kumar2★ Corresponding author

    1. 1Departments of Pharmacology, All India Institute of Medical Sciences, New Delhi, INDIA.
    2. 2Departments of Rheumatology, All India Institute of Medical Sciences, New Delhi, INDIA.

    CORRESPONDENCE

    Surender Singh

    Departments of Pharmacology, All India Institute of Medical Sciences, New Delhi, INDIA.

    surenderaiims@gmail.com

    Volume 10, Issue 3 · pp. 301–308 · PUBLISHED · DOI: 10.4103/pr.pr_159_17

    View on Pharmacogn. Res. original site ↗

    ABSTRACT

    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 4th day along with pretreatment with different doses of TBE (100 mg/kg, 200 mg/kg, and 400 mg/kg, p.o) given from 1st to 15th 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 < 0.001) in oxidative stress and biochemical parameters – AST (63.94 IU/L), ALT (55.98 IU/L), BUN (37.02 mg/dl), and creatinine (1.065 mg/dl). Pretreatment with TBE 400 mg/kg, histopathology of both liver and kidney tissues showed improved architectural damage and immunohistochemistry showed downregulation of increased antigens‑caspase‑3 and NFkB. 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.

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      Chauhan, P., Sharma, H., Singh, S., Gupta, Y. K., & Kumar, U. (). Attenuation of Methotrexate‑induced Hepatorenal Damage by Terminalia bellerica Fruit Extract in Experimental Rats. Pharmacognosy Research, 10(3), 301–308. https://doi.org/10.4103/pr.pr_159_17