title: Hepatocyte-protective and anti-oxidant effects of rifampicin on human chronic hepatitis C and murine acute hepatocyte disorder.
abstract: Rifampicin (RFP) is a semisynthetic antibiotic derived from the rifamycins and is one of the most commonly used pharmaceutical compounds worldwide in the treatment of tuberculosis. We previously reported that low-dose and long-term oral administration of RFP to 6 hepatitis C virus-related liver cirrhosis patients who were at high risk for presenting with hepatocellular carcinoma (HCC) resulted in a marked suppression of the occurrence of HCC without showing an adverse effect. The underlying mechanism was found to be due to the anticancer effect based on the potent anti-angiogenic properties of RFP. The present study revealed that RFP has an additional hepatocyte-protective effect by lowering the release of hepatic enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in chronic hepatitis C patients. Experimentally, we were able to show that RFP had hepatocyte-protective effects in acute hepatocyte disorder models of mice and rats induced by concanavalin A and by D-galactosamine, respectively: RFP significantly prevented an increase in the levels of ALT, AST and lactate dehydrogenase in these animal models. In addition, we found that RFP had a strong anti-oxidant action which was approximately three times stronger than the action of silibinin, an anti-inflammatory agent of human hepatic stellate cells, implicating that the hepatocyte-protective effects of RFP are mediated by its anti-oxidant activity. These results reveal that oral administration of RFP exerts not only a prophylactic effect on the occurrence or recurrence of HCC for an extensive period of time, but also exerts hepatocyte-protective effects on both human chronic hepatitis C and acute hepatocyte disorder in rodent models, and the anti-oxidant activity of RFP is implicated to participate in the latter effects.
authors.affiliation: GeneCare Research Institute Co., Ltd., Kamakura 247-0063;
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kataoka
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kono
authors.forename: Masanobu
authors.initials: M
authors.lastname: Sugimoto
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Furuichi
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Shichiri
authors.forename: Yujiro
authors.initials: Y
authors.lastname: Tanaka