Kataoka Kazuhiro, Kono Yutaka, Sugimoto Masanobu, Furuichi Yasuhiro, Shichiri Masayoshi, Tanaka Yujiro
GeneCare Research Institute Co., Ltd., Kamakura 247-0063;
Exp Ther Med. 2010 Nov;1(6):1041-1047. doi: 10.3892/etm.2010.159. Epub 2010 Sep 29.
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.
利福平（RFP）是一种从利福霉素衍生而来的半合成抗生素，是全球治疗结核病最常用的药物化合物之一。我们之前报道，对6名有肝细胞癌（HCC）高风险的丙型肝炎病毒相关肝硬化患者进行低剂量长期口服利福平，可显著抑制HCC的发生，且未显示出不良反应。发现其潜在机制是基于利福平强大的抗血管生成特性的抗癌作用。本研究表明，利福平通过降低慢性丙型肝炎患者肝酶丙氨酸转氨酶（ALT）和天冬氨酸转氨酶（AST）的释放，具有额外的肝细胞保护作用。在实验中，我们能够证明利福平分别在伴刀豆球蛋白A和D-半乳糖胺诱导的小鼠和大鼠急性肝细胞损伤模型中具有肝细胞保护作用：在这些动物模型中，利福平显著阻止了ALT、AST和乳酸脱氢酶水平的升高。此外，我们发现利福平具有很强的抗氧化作用，其强度约为人类肝星状细胞抗炎剂水飞蓟宾作用的三倍，这表明利福平的肝细胞保护作用是由其抗氧化活性介导的。这些结果表明，口服利福平不仅在很长一段时间内对HCC的发生或复发具有预防作用，而且对人类慢性丙型肝炎和啮齿动物模型中的急性肝细胞损伤均具有肝细胞保护作用，且利福平的抗氧化活性参与了后者的作用。
