Hepatoprotective Effects of Azadirachta indica (Neem) Leaf Extract Against Rifampicin-Induced Hepatotoxicity in Wistar Rats

Background: Rifampicin-induced hepatotoxicity is a significant clinical challenge in tuberculosis management, contributing to treatment interruption and mortality. Azadirachta indica (neem) is a Nigerian medicinal plant with reported antioxidant and hepatoprotective activities. Scientific investigation of its protective potential against drug-induced liver injury may have clinical relevance, particularly in high-TB burden settings. This study evaluated the hepatoprotective activity of A. indica leaf extract against rifampicin-induced hepatotoxicity in Wistar rats. Methods: Thirty-six Wistar rats were allocated into six groups: normal control, rifampicin-treated (100 mg/kg for 28 days), silymarin reference group (100 mg/kg), and three extract co-treatment groups (100, 250, 500 mg/kg). Liver function tests (ALT, AST, ALP, total bilirubin), oxidative stress markers, and histopathological assessment of liver tissue were performed at termination. Results: Rifampicin induced significant elevations in ALT, AST, and bilirubin (p less than 0.001). A. indica co-treatment at 500 mg/kg significantly attenuated these elevations and reduced MDA levels while restoring GSH and CAT activities. Liver histology showed near-normal hepatocyte morphology in the high-dose extract group compared to marked necrosis in the rifampicin-only group. Conclusion: A. indica leaf extract exhibits significant hepatoprotective activity against rifampicin-induced liver damage. Its potential as adjunct therapy in tuberculosis management deserves further clinical investigation. Keywords: Azadirachta indica, hepatoprotective, rifampicin, hepatotoxicity, liver function