Evaluation of hepatotoxicity and oxidative stress in rats treated with tert-butyl hydroperoxide

Abstract

Although tert-butyl hydroperoxide (t-BHP) is commonly used to induce oxidative stress, little is known about the time- or dose-dependence of its oxidative effects. In this study, we examined hepatotoxicity and oxidative stress in male rats at various times (0-24. h) after t-BHP (0, 0.2, 0.5, 1 or 3. mmol/kg, ip) treatment. Serum hepatotoxicity parameters were increased from 2. h following 1. mmol/kg t-BHP and reached their maximum values at 8. h. Plasma malondialdehyde levels were maximally elevated by 62% at 0.5. h and returned to control levels by 4. h. Hepatic glutathione levels were decreased between 0.5 and 2. h, and hepatic glutathione disulfide levels were increased at 2. h. Interestingly, hepatic glutathione levels were increased at 24. h, which may be attributed to up-regulation of glutathione synthesis through induction of gamma-glutamylcysteine ligase expression. The elevation of hepatotoxic parameters and plasma MDA was observed from 0.5 to 1. mmol/kg t-BHP, respectively, in a dose-dependent manner. Considering that the maximal dose resulted in 20% lethality, 1. mmol/kg of t-BHP may be suitable for evaluating antioxidant activity of tested compounds. Our results provide essential information to characterize the t-BHP-induced oxidative stress and hepatotoxicity.