title: Exogenous hydrogen sulfide protects against high glucose‑induced inflammation and cytotoxicity in H9c2 cardiac cells.
abstract: Hyperglycemia serves an important role in the pathogenesis of diabetic cardiomyopathy. The aim of the present study was to investigate whether exogenous hydrogen sulfide (H2S) protects against high glucose‑induced inflammation and cytotoxicity in cardiac cells by inhibiting the p38 mitogen‑activated protein kinase (MAPK)/nuclear factor‑κB (NF‑κB), cyclooxygenase‑2 (COX‑2) and inducible nitric oxide synthase (iNOS) signaling pathways. Rat H9c2 myocardium cells were exposed to 33 mM glucose (high glucose, HG) for 24 h to stimulate HG‑induced cytotoxicity. One group of cells was pretreated with NaHS (a donor of H2S) prior to HG exposure, and cell viability was determined using the Cell Counting Kit‑8 assay. The protein expression levels of p38MAPK, the phosphorylated p65 subunit of NF‑κB, iNOS, COX‑2 and caspase‑3 were analyzed by western blotting, and the protein expression levels of interleukin (IL)‑1β and IL‑6 were detected by enzyme‑linked immunosorbent assay (ELISA). Pretreatment of H9c2 cells with NaHS for 30 min prior to exposure to HG significantly ameliorated the expression of p38MAPK and NF‑κB. In addition, pretreatment with NaHS markedly attenuated p38MAPK/NF‑κB‑mediated cytotoxicity and inflammation, as evidenced by the significant increase in cell viability and decrease in iNOS, COX‑2, IL‑1β and IL‑6 expression levels. Furthermore, treatment of cells with NaHS significantly decreased the expression of caspase‑3, which suggested that NaHS attenuated HG‑induced apoptosis. In conclusion, the results of the present study provided evidence to suggest that exogenous H2S protects against HG‑induced cytotoxicity and inflammation in H9c2 cardiac cells. H2S may exert these cytoprotective effects via inhibition of the p38MAPK/NF‑κB, COX‑2 and iNOS signaling pathways.
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China.
authors.forename: Zena
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China.
authors.forename: Xiaobian
authors.initials: X
authors.lastname: Dong
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhuang
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China.
authors.forename: Xun
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China.
authors.forename: Lichun
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China.
authors.forename: Xinxue
authors.initials: X
authors.lastname: Liao
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D007249:Inflammation / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D016328:NF-kappa B; D020011:Protective Agents; D048051:p38 Mitogen-Activated Protein Kinases; D053148:Caspase 3; D005947:Glucose; D006862:Hydrogen Sulfide