Background: Isoniazid (INH) is a first-line antitubercular drug; however, its clinical use may be complicated by drug-induced liver injury, associated with oxidative stress and disruption of hepatic homeostasis. Betaine is a naturally occurring methyl donor with reported antioxidant and hepatoprotective properties. This study evaluated the protective effects of different betaine doses against INH-induced hepatic injury in rats.
Methods: Sixty adult male Wistar rats were randomly divided into six experimental groups, with 10 animals per group: control, INH (300 mg/kg/day), INH plus betaine (10, 50, or 100 mg/kg/day), and betaine alone (100 mg/kg/day). Treatments were administered orally for 14 consecutive days, with betaine given 1 h before INH. Serum biochemical markers, including alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase, total bilirubin, and total protein, were evaluated. Hepatic glutathione (GSH), malondialdehyde (MDA), reactive oxygen species (ROS), and ferric reducing antioxidant power (FRAP) were measured. Liver alterations were assessed by hematoxylin and eosin (H&E) staining.
Results: INH administration significantly elevated serum ALT, AST, ALP, LDH, and total bilirubin levels, while reducing total protein, GSH, and FRAP and increasing hepatic ROS and MDA levels. Betaine at 10, 50, and 100 mg/kg significantly attenuated these biochemical and oxidative alterations and improved hepatic histopathology, without significant effects when administered alone.
Conclusion: Betaine attenuated INH-induced biochemical, oxidative, and histopathological alterations in rat liver, suggesting that preservation of hepatic redox homeostasis may contribute to its hepatoprotective effects. These findings support further preclinical investigation of betaine as a potential adjunctive strategy for limiting INH-associated hepatotoxicity.
Mechanistic and Translational Relevance: The hepatoprotective effects of betaine were accompanied by restoration of hepatic redox homeostasis, characterized by increased GSH and FRAP and reduced ROS and MDA levels. These findings provide a mechanistically informed basis for further preclinical investigation of betaine as a potential adjunctive strategy for attenuating INH-associated hepatotoxicity.