Evaluation of Isoniazid-Induced Toxicity in a Murine Model of Metabolic Syndrome

Abstract

Background: Isoniazid (INH) is an essential antitubercular drug, but its use may cause adverse effects, particularly hepatotoxicity. Metabolic syndrome may increase susceptibility to drug-induced organ injury through oxidative stress, inflammation, and metabolic dysfunction. This study evaluated the toxic effects of different doses of INH in mice with experimentally induced metabolic syndrome. Methods: Fifty adult male Swiss albino mice were randomly allocated into six groups. Metabolic syndrome was induced using monosodium glutamate (MSG; 4.16 mg/g) for 41.6 days, followed by INH administration at 26, 52, or 104 mg/kg for 10.4 days. Body weight, food and water intake, fasting blood glucose, Mouse Grimace Scale, general toxicity signs, and survival were monitored. Serum ALT, AST, creatinine, and BUN were measured to assess hepatic and renal function. Results: INH produced dose-dependent toxicity, with the greatest effects observed in the MSG+104 mg/kg INH group. This group showed increased fasting glucose, behavioral distress, ALT, AST, creatinine, and BUN, accompanied by reduced food intake and survival. Moderate changes were observed at the intermediate INH dose. Conclusion: INH toxicity was enhanced in mice with metabolic syndrome, particularly at higher doses, indicating increased hepatic, renal, metabolic, and systemic vulnerability.