Studies on toxicity of antitubercular drugs namely isoniazid, rifampicin, and pyrazinamide in an in vitro model of HepG2 cell line

摘要

Antitubercular drugs (ATT) are known to be majorly metabolized and detoxified in liver by both Phase I and Phase II group of drug metabolizing enzymes. These drugs as well as their metabolites are toxic and during this process cause injury to liver. In this study, we have investigated the in vitro hepatotoxic potential of both individual as well as combination ATT drugs using an in vitro model of human hepatocellular carcinoma cell line (HepG2). The cells were treated with varied concentrations of ATT drugs namely isoniazid (INH), rifampicin (RIF), and pyrazinamide (PYZ) for different durations. Cytotoxicity assay using MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazoliumbromide) as well as morphological analysis using phase contrast microscopy have shown that concentrations used were not cytotoxic. However, pre-treatment with sub-cytotoxic concentrations of INH and PYZ increased the toxicity with the same drugs. This report corroborates the clinical finding that long-term treatment as well combination drug therapy with ATT induces hepatotoxicity rather than individual drugs.