The Molecular Mechanisms of the Hepatoprotective Effect of Gomisin A against Oxidative Stress and Inflammatory Response in Rats with Carbon Tetrachloride-Induced Acute Liver Injury

Oxidative damage and inflammation are implicated in the pathogenesis of liver injury and fibrosis. In the present study, we investigated the molecular mechanism by which gomisin A conferred a hepatoprotective effect, focusing on its antioxidant and anti-inflammatory effects using rats with carbon tetrachloride (CCl4)-induced acute liver injury. Pretreatment with gomisin A prior to the administration of CCl4 markedly prevented an increase in alanine aminotransferase, aspartate aminotransferase, and histological hepatic lesions. Gomisin A was also associated with a decrease in hepatic lipid peroxidation, and increased superoxide dismutase activity, suggesting that gomisin A has an antioxidant effect. In addition gomisin A treatment ameliorated mRNA levels of CCl4-induced inflammatory mediators, including tumor necrosis factor-alpha, interleukin-1 beta and inducible nitric oxide (NO) synthase, and the protein levels of transcriptional upregulator nuclear factor kappa B (NF-kappa B) and phospho-inhibitor of NF-kappa B (I kappa B). Furthermore, alpha-smooth muscle actin (alpha-SMA), a myofibroblast marker, was also inhibited by gomisin A treatment. These results suggest that gomisin A inhibits the oxidative stress and activation of NF-kappa B, leading to down-regulation of pro-inflammatory mediators and amelioration of fibrogenesis.