The antioxidant effect of DL-alpha-lipoic acid on copper-induced acute hepatitis in Long-Evans Cinnamon (LEC) rats

The Long-Evans Cinnamon (LEC) rats, due to a genetic defect, accumulate exc ess copper (Cu) in the liver in a manner similar to patients with Wilson's disease and spontaneously develop acute hepatitis with severe jaundice. In this study we examined the protective effect of DL-a-Lipoic acid (LA) again st acute hepatitis in LEC rats. LA was administered to LEC rats by gavage i n doses of 10, 30 and 100 mg/kg five times per week, starting at 8-weeks-ol d and continuing till 12-weeks-old. Although LA had little effect against t he increases in serum transaminase activities, it suppressed the loss of bo dy weight and prevented severe jaundice in a dose-dependent manner. Antioxi dant system analyses in liver showed that LA treatment significantly suppre ssed the inactivations of catalase and glutathione peroxidase, and the indu ction of heme oxygenase-l, an enzyme which is inducible under oxidative str ess. Furthermore, LA showed dose-dependent suppressive effect against incre ase in nonheme iron contents of both cytosolic and crude mitochondrial frac tions in a dose-dependent manner. Although at the highest dose, LA slightly suppressed the accumulation of Cu in crude mitochondrial fraction, it had no effect on the accumulation of Cu in cytosolic fraction. While LA complet ely suppressed the increase in lipid peroxidation (LPO) in the microsomal f raction at the highest dose, the suppressive effect against LPO in crude mi tochondrial fractions was slight. From these results, it is concluded that LA has antioxidant effects at the molecular level against the development o f Cu-induced hepatitis in LEC rats. Moreover, mitochondrial oxidative damag e might be involved in the development of acute hepatitis in LEC rats.