Hydrogen sulfide attenuates doxorubicin-induced cardiotoxicity by inhibition of the p38 MAPK pathway in H9c2 cells

  • Authors:
    • Runmin Guo
    • Jiancong Lin
    • Wenming Xu
    • Ning Shen
    • Liqiu Mo
    • Changran Zhang
    • Jianqiang Feng
  • View Affiliations

  • Published online on: January 15, 2013     https://doi.org/10.3892/ijmm.2013.1246
  • Pages: 644-650
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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.

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March 2013
Volume 31 Issue 3

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Guo R, Lin J, Xu W, Shen N, Mo L, Zhang C and Feng J: Hydrogen sulfide attenuates doxorubicin-induced cardiotoxicity by inhibition of the p38 MAPK pathway in H9c2 cells. Int J Mol Med 31: 644-650, 2013
APA
Guo, R., Lin, J., Xu, W., Shen, N., Mo, L., Zhang, C., & Feng, J. (2013). Hydrogen sulfide attenuates doxorubicin-induced cardiotoxicity by inhibition of the p38 MAPK pathway in H9c2 cells. International Journal of Molecular Medicine, 31, 644-650. https://doi.org/10.3892/ijmm.2013.1246
MLA
Guo, R., Lin, J., Xu, W., Shen, N., Mo, L., Zhang, C., Feng, J."Hydrogen sulfide attenuates doxorubicin-induced cardiotoxicity by inhibition of the p38 MAPK pathway in H9c2 cells". International Journal of Molecular Medicine 31.3 (2013): 644-650.
Chicago
Guo, R., Lin, J., Xu, W., Shen, N., Mo, L., Zhang, C., Feng, J."Hydrogen sulfide attenuates doxorubicin-induced cardiotoxicity by inhibition of the p38 MAPK pathway in H9c2 cells". International Journal of Molecular Medicine 31, no. 3 (2013): 644-650. https://doi.org/10.3892/ijmm.2013.1246