Hepatoprotective Effects of Montelukast Against Methotrexate Toxicity in Rat– An Experimental Research
Abstract
Methotrexate, a widely utilized antineoplastic and immunosuppressive agent, is associated with significant adverse effects including hepatotoxicity and myelosuppression across various malignancies and autoimmune conditions. This experimental investigation evaluated the potential hepatoprotective properties of montelukast in mitigating methotrexate-induced hepatic injury. Thirty male Wistar rats were randomly allocated into five groups (n=6 per group). Group 1 served as the negative control, receiving equivalent volumes of normal saline. Group 2 (montelukast control) received montelukast 10 mg/kg body weight intraperitoneally from day 4 to day 10. Groups 3, 4, and 5 received a single intraperitoneal dose of methotrexate 20 mg/kg body weight on day 0 to induce hepatotoxicity. Groups 4 and 5 additionally received montelukast 5 mg/kg and 10 mg/kg body weight respectively, administered intraperitoneally from day 4 for seven consecutive days following methotrexate treatment. Biochemical analysis revealed that montelukast co-administration resulted in dose-dependent improvements in hepatic function parameters. Serum levels of total cholesterol, high-density lipoprotein cholesterol, total bilirubin, alanine aminotransferase, aspartate aminotransferase, total proteins, albumin, and globulin demonstrated significant amelioration correlating with increasing montelukast dosage compared to methotrexate monotherapy. These findings suggest that montelukast exhibits hepatoprotective activity against methotrexate-induced liver injury, potentially through modulation of hepatic enzyme levels and preservation of hepatocellular function. Montelukast may represent a promising adjuvant therapy to mitigate hepatotoxicity associated with methotrexate treatment. Further clinical investigation is warranted to validate these preclinical observations in human subjects.
Keywords:
Hepatoprotective Effect, Montelukast, Methotrexate Induced Toxicity
