title: Hydrogen sulfide attenuates doxorubicin-induced cardiotoxicity by inhibiting reactive oxygen species-activated extracellular signal-regulated kinase 1/2 in H9c2 cardiac myocytes.
abstract: Doxorubicin (DOX) is a potent and available antitumor therapeutic agent; however, its clinical application is limited due to its cardiotoxicity. Preliminary evidence suggests that hydrogen sulfide (H2S) may exert protective effects on DOX‑induced cardiotoxicity. Therefore, the aim of the present study was to investigate whether the extracellular signal‑regulated kinase (ERK) 1/2 signaling pathway is involved in the cardioprotection of H2S against DOX‑induced cardiotoxicity. The present study demonstrated that pretreatment with sodium hydrosulﬁde (NaHS; a donor of H2S) prior to DOX exposure attenuated the decreased cell viability, the increased apoptosis rate and the intracellular accumulation of reactive oxygen species (ROS) in H9c2 cardiac myocytes. Exposure of H9c2 cardiac myocytes to DOX upregulated the expression levels of phosphorylated ERK1/2, which had been reduced by pretreatment with NaHS or N‑acetyl‑L‑cysteine, a ROS scavenger. In addition, H2S upregulated the anti‑apoptotic protein, Bcl‑2 and downregulated the pro‑apoptotic protein, Bax. Notably, U0126, a selective inhibitor of ERK1/2, was observed to mimic the above‑mentioned cytoprotective activity of H2S. In conclusion, these findings indicate that H2S attenuates DOX‑induced cardiotoxicity by inhibiting ROS-mediated activation of ERK1/2 in H9c2 cardiac myocytes.
authors: Department of Clinical Laboratory, Affiliated Nanhua Hospital, University of South China, Hengyang, Hunan 421001, P.R. China.
authors: Mi-Hua
authors: MH
authors: Liu
authors: Department of Pathology, The Third People's Hospital of Huizhou, Huizhou, Guangdong 516002, P.R. China.
authors: Xiao-Long
authors: XL
authors: Lin
authors: Department of Pathology, Mawangdui Hospital, Changsha, Hunan 410016, P.R. China.
authors: Yuan
authors: Y
authors: Zhang
authors: Department of Clinical Laboratory, Affiliated Nanhua Hospital, University of South China, Hengyang, Hunan 421001, P.R. China.
authors: Jun
authors: J
authors: He
authors: Department of Clinical Laboratory, Affiliated Nanhua Hospital, University of South China, Hengyang, Hunan 421001, P.R. China.
authors: Tian-Ping
authors: TP
authors: Tan
authors: Department of Clinical Laboratory, Affiliated Nanhua Hospital, University of South China, Hengyang, Hunan 421001, P.R. China.
authors: Shao-Jian
authors: SJ
authors: Wu
authors: Department of Clinical Laboratory, Affiliated Nanhua Hospital, University of South China, Hengyang, Hunan 421001, P.R. China.
authors: Jun
authors: J
authors: Liu
authors: Department of Clinical Laboratory, Affiliated Nanhua Hospital, University of South China, Hengyang, Hunan 421001, P.R. China.
authors: Wei
authors: W
authors: Tian
authors: Department of Clinical Laboratory, Affiliated Nanhua Hospital, University of South China, Hengyang, Hunan 421001, P.R. China.
authors: Li
authors: L
authors: Chen
authors: Department of Clinical Laboratory, Affiliated Nanhua Hospital, University of South China, Hengyang, Hunan 421001, P.R. China.
authors: Shan
authors: S
authors: Yu
authors: Department of Ultrasonic Diagnosis, Boai Hospital of Zhongshan, Zhongshan, Guangdong 528403, P.R. China.
authors: Jian
authors: J
authors: Li
authors: Department of Cardiology, The First Hospital of Changsha, Changsha, Hunan 410005, P.R. China.
authors: Cong
authors: C
authors: Yuan
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002460:Cell Line; D003542:Cystathionine gamma-Lyase / Q000378:metabolism; D004317:Doxorubicin / Q000633:toxicity*; D004353:Drug Evaluation, Preclinical; D004789:Enzyme Activation; D016166:Free Radical Scavengers / Q000494:pharmacology; D006331:Heart Diseases / Q000139:chemically induced / Q000517:prevention & control; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D020935:MAP Kinase Signaling System; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000903:Antibiotics, Antineoplastic; D002316:Cardiotonic Agents; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D004317:Doxorubicin; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D003542:Cystathionine gamma-Lyase; D000111:Acetylcysteine; D006862:Hydrogen Sulfide