Protective effect of curcumin, silymarin and N-acetylcysteine on antitubercular drug-induced hepatotoxicity assessed in an in vitro model.
Tuberculosis (TB) is highly endemic in India. The first-line anti-TB therapy (ATT) involving isoniazid (INH), rifampicin and pyrazinamide causes hepatotoxicity in approximately 11.5% of Indian patients. Studies have shown that ATT-induced hepatotoxicity is primarily due to oxidative stress caused by the drugs and metabolites. Herbal drugs with antioxidative properties have been tested in animal studies and clinical trials for the management of hepatotoxicity. The objective of this study was to investigate the role of curcumin (CUR), silymarin (SILY) and N-acetylcysteine (N-ACET) on hepatotoxicity by ATT drugs using an in vitro model of human hepatocellular carcinoma cell line (HepG2). HepG2 cells were treated with ATT drugs alone or along with CUR, SILY or N-ACET for a 48-h duration. The cells were monitored for viability, morphology, respiring mitochondria and cell cycle. Our results suggest that the presence of hepatoprotective drugs during treatment of HepG2 cells with ATT drugs lowers the hepatotoxic effect of the latter. This is observed in terms of (a) increased cell viability, (b) healthy-looking cell morphology as revealed by phase contrast microscopy, (c) active respiring cells as observed with confocal microscopy upon staining with a mitochondrial membrane-specific dye, MitoTracker(®) Red, and reduction in the sub-G(1) peak in cell cycle analysis by flow cytometry. Our results suggest that these hepatoprotective drugs need to be further explored as potential adjuvant therapy along with ATT drugs.
Department of Chemical Engineering, Indian Institute of Technology Bombay, Powai, Mumbai, Maharashtra, India.
M
M
Singh
P
P
Sasi
V H
VH
Gupta
G
G
Rai
D N
DN
Amarapurkar
P P
PP
Wangikar
D000111:Acetylcysteine / Q000494:pharmacology*; D000995:Antitubercular Agents / Q000009:adverse effects*; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000209:etiology; D003474:Curcumin / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D007538:Isoniazid / Q000009:adverse effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology*; D011718:Pyrazinamide / Q000009:adverse effects; D012838:Silymarin / Q000494:pharmacology*
D000995:Antitubercular Agents; D020011:Protective Agents; D012838:Silymarin; D011718:Pyrazinamide; D003474:Curcumin; D007538:Isoniazid; D000111:Acetylcysteine