title: Hydrogen sulfide attenuates doxorubicin-induced cardiotoxicity by inhibition             of the p38 MAPK pathway in H9c2 cells.
abstract: We previously demonstrated the protective effect of hydrogen sulfide (H2S)             against doxorubicin (DOX)-induced cardiotoxicity through inhibition of endoplasmic             reticulum stress. The aim of the present study was to explore the role of p38             mitogen-activated protein kinase (MAPK) in DOX-induced cardiotoxicity and ascertain             whether exogenous H2S protects DOX-induced injury by inhibiting p38 MAPK in cardiomyoblasts             (H9c2). We observed that exposure of H9c2 cells to 5 µM DOX not only markedly             induced injuries, including cytotoxicity, apoptosis, overproduction of reactive             oxygen species (ROS) and dissipation of mitochondrial membrane potential (MMP),             but also enhanced the expression level of phosphorylated (p)-p38 MAPK. The DOX-induced             increase in expression of p-p38 MAPK was significantly attenuated by pretreatment             of H9c2 cells with either 400 µM sodium hydrogen sulfide (NaHS) (a donor of H2S)             or 1,000 µM N-acetyl-L-cysteine (NAC, an ROS scavenger) prior to exposure to DOX.             Pretreatment with either 400 µM NaHS or 3 µM SB203580, a selective inhibitor of             p38 MAPK, ameliorated DOX-induced cardiomyocyte injuries, as evidenced by an increase             in cell viability, and decreases in the number of apoptotic cells, ROS generation             as well as dissipation of MMP. In conclusion, the findings of the present study             demonstrated that the activation of p38 MAPK contributes to DOX-induced injuries,             including cytotoxicity, apoptosis, mitochondrial damage and oxidative stress in             H9c2 cells. We also provide novel evidence that exogenous H2S protects H9c2 cells             against DOX-induced cardiotoxicity by inhibition of the p38 MAPK pathway.
authors: Department of Physiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, PR China.
authors: Runmin
authors: R
authors: Guo
authors: Jiancong
authors: J
authors: Lin
authors: Wenming
authors: W
authors: Xu
authors: Ning
authors: N
authors: Shen
authors: Liqiu
authors: L
authors: Mo
authors: Changran
authors: C
authors: Zhang
authors: Jianqiang
authors: J
authors: Feng
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D054715:Cardiotoxins; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000009:adverse effects*; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism
chemical_list: D054715:Cardiotoxins; D007093:Imidazoles; D011725:Pyridines; D017382:Reactive Oxygen Species; D004317:Doxorubicin; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580; D000111:Acetylcysteine; D006862:Hydrogen Sulfide