title: Protective effects of hydrogen sulfide on oxidative stress 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 H2S inhibits proliferation and induces cell cycle arrest and apoptosis in activated HSCs and attenuates CCl4-induced hepatic fibrosis and ECM expression.
authors.affiliation: Department of Hepatopancreatobiliary Surgery, Affiliated Hospital of Qinghai University, Xining, Qinghai 810001, PR China.
authors.forename: Hai-Ning
authors.initials: HN
authors.lastname: Fan
authors.forename: Hai-Jiu
authors.initials: HJ
authors.lastname: Wang
authors.forename: Cai-Rang
authors.initials: CR
authors.lastname: Yang-Dan
authors.forename: Li
authors.initials: L
authors.lastname: Ren
authors.forename: Cong
authors.initials: C
authors.lastname: Wang
authors.forename: Yan-Fei
authors.initials: YF
authors.lastname: Li
authors.forename: Yong
authors.initials: Y
authors.lastname: Deng
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D024042:Collagen Type I / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004195:Disease Models, Animal; D005355:Fibrosis; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D055166:Hepatic Stellate Cells / Q000187:drug effects* / Q000378:metabolism*; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013440:Sulfides / Q000494:pharmacology
chemical_list: D024042:Collagen Type I; D017382:Reactive Oxygen Species; D013440:Sulfides; C025451:sodium bisulfide; D002118:Calcium; D006862:Hydrogen Sulfide