Nrf2mediated antioxidant effects contribute to suppression of nonalcoholic steatohepatitis associated hepatocellular carcinoma in murine model

The exact mechanisms of hepatocellular carcinoma development in nonalcoholic steatohepatitis remain unclear. In this study, we used a new class of highfat diet, which could induce hepatocellular carcinoma development without the use of general chemical carcinogens or knockout mice. We investigated the correlation between hepatocellular carcinoma and oxidative stress/anti oxidant effects after depletion of the gut microbiota by treatment with antibiotics. Mice fed with the steatohepatitisinducing high fat diet (STHD01) for 41 weeks developed hepatocellular carci noma. Antibiotictreatment in mice fed with STHD01 significantly depleted the gut microbiota and significantly ameliorated liver injury/histology. The tumor numbers of hepatocellular carcinoma were dramatically decreased by the antibioticstreatment. We analyzed the factors involved in oxidative stress and antioxidant effects. Oxidative stress was elevated in mice fed with STHD01, whereas some antioxidant factors were significantly elevated after antibiotics treatment. These results suggest that the gut microbiota is a key factor in improving oxidative stress induced by STHD01 feeding.