Protective effects of hydrogen sulfide on oxidativestress and fibrosis in hepatic stellate cells

Abstract

In hepatic fibrosis, hepatic stellate cells (HSCs) are activated and change into myofibroblast-like cells which are characterized by increased proliferation and extracellular matrix (ECM) synthesis. In this study, we investigated the regulatory effects of hydrogen sulfide (H2S) on hepatic fibrosis. We detected the proliferation, cell cycle progression, apoptosis, intracellular reactive oxygen species (ROS) and free calcium levels in ferric nitrilotriacetate (Fe-NTA)-activated HSCs treated with sodium hydrogen sulphide (NaHS), an H2S-releasing molecule. We also evaluated the effects of NaHS on fibrosis and ECM synthesis in rats with hepatic fibrosis induced by carbon tetrachloride (CCl4). MTT assay revealed that NaHS (500 μmol/l) suppressed the Fe-NTA-induced proliferation of HSC-T6 cells in a dose-dependent manner. NaHS induced G1 phase cell cycle arrest and apoptosis in the Fe-NTA-treated HSC-T6 cells. Furthermore, in the Fe-NTA-treated HSC-T6 cells, NaHS reduced intracellular levels of ROS at 1, 3 and 6 h and reduced intracellular free calcium levels at 3 and 6 h. H2S administration attenuated hepatic fibrosis and collagen I protein expression in the rats with CCl4-induced hepatic fibrosis. In conclusion, exogenous H 2S inhibits proliferation and induces cell cycle arrest and apoptosis in activated HSCs and attenuates CCl4-induced hepatic fibrosis and ECM expression. © 2013 Spandidos Publications Ltd.