Effects of N-acetylcysteine on oxidative stress in rats with nonalcoholic steatohepatitis

Abstract

The study was conducted to prove the attenuated effects of N-acetylcysteine (NAC) on oxidative stress in rats with nonalcoholic steatohepatitis (NASH). Male Sprague-Dawley rats were randomly divided into five groups. Group 1 (normal control) was fed regular dry rat chow (RC) for 6 weeks. Group 2 (NASH) was fed 100% fat diet for 6 weeks. Group 3-5 were fed 100% fat diet for 6 weeks, and then switched to RC alone (NASH+diet; group 3), to RC+20 mg/kg/day of NAC orally (NASH+diet+NAC₂₀ ; group 4) or to RC+500 mg/kg/day of NAC orally (NASH+diet+NAC₅₀₀ ; group 5) for 4 weeks, respectively. They were sacrificed to collect blood, and liver samples at the end of the study. The results showed that levels of total glutathione (GSH), serum cholesterol, and hepatic malondialdehyde (MDA) were increased significantly in NASH group as compared with normal control. Liver histopathology from group 2 showed moderate to severe macrovesicular steatosis, hepatocyte ballooning, and necroinflammation. Treatment with diet or diet plus NAC reduced the levels of GSH, cholesterol, and hepatic MDA back to normal. Liver sections from group 3-5 showed a decrease in fat deposition and necroinflammation in hepatocytes. However, no differences on all variables existed between diet alone or diet plus NAC groups. Our data indicate that diet or diet plus NAC treatment could attenuate oxidative stress and improve liver histopathology of NASH. However, the addition of NAC is not better than diet treatment alone.