Hepatoprotective Potential of Micronutrients Against Methotrexate-Induced Hepatotoxicity in Experimental Mice Model

Objective: To evaluate the hepatoprotective role of micronutrients, ascorbic acid and alpha-tocopherol, against methotrexate (MTX)-induced hepatic damage in mice. Methodology: A laboratory-based experimental study was carried out at Foundation University Medical College in collaboration with the National Institute of Health, Islamabad, from October to December 2021. Twenty-four male BALB/c mice were randomly divided into four groups (n=6). Group I received intraperitoneal normal saline. Group II received a single intraperitoneal injection of MTX at a dose of 20 mg/kg. Groups III and IV were given oral ascorbic acid (200 mg/kg) and oral alpha-tocopherol (100 mg/kg) respectively, both for 7 days, with MTX administered on day 4. Blood and liver samples were collected 24 hours after the last dose for evaluation of hepatic serum biomarkers and histological analysis, respectively. Results: Ascorbic acid demonstrated a protective effect against MTX-induced hepatic damage. However, alpha-tocopherol did not show hepatoprotection on liver histopathology. Conclusion: Ascorbic acid exhibits protective potential when administered concomitantly with MTX. However, alpha-tocopherol does not provide complete hepatoprotection against MTX-induced liver injury.