Synergic effects of α-tocopherol and β-carotene on tert-butylhydroperoxide-induced HepG2 cell injury

Oxidative stress produced by the dietary or chemical substrates is one of the major causes of liver cell injury. In this study, we compared the effects of two dietary antioxidants, α-tocopherol (α-T) and β-carotene (β-C) against tert-butyl hydroperxide (tBHP)-induced oxidative stress in human hepatoma HepG2 cells. Cell proliferation, lipid peroxidation (LPO), cellular lactate dehydrogenase (LDH), [3H]-aflatoxin B1(AFB1)-DNA adduct formation, and cytochrome P450 2E1 (CYP2E1) expression were determined after antioxidants were added to the tBHP-stressed cells. When compared to an ethanol-based control, all biomarkers for the cell damage were significantly increased by treatments. Treat-ments of β-C or the combination of two antioxidants at 50 ppm for 48 h enhanced cell proliferation (P < 0.05) compared to tBHP control. The antioxidative and cytoprotective actions of α-T and β-C, alone or in combination, were associated with modulation of microsomal CYP2E1 expression, corre-sponding to the regulation of LPO production (P < 0.0001). Our results indicate that α-T and β-C may contribute differently to protection of cellular membrane disruption in CYP2E1-expressing HepG2 cells. Moreover, the combination of α-T and β-C appears to impel the greater protection of pathogenic processes of oxidative stress in liver. Toxicology and Industrial Health 2009; 25: 311–320. Key words: CYP2E1; DNA adduction; HepG2; α-tocopherol; β-caroten