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Exogenous hydrogen sulfide protects against hepatic ischemia/reperfusion injury by inhibiting endoplasmic reticulum stress and cell apoptosis

  • Authors:
    • Liang Chen
    • Keqiang Ma
    • Haining Fan
    • Xiaolong Wang
    • Tiansheng Cao
  • View Affiliations / Copyright

    Affiliations: Department of General Surgery, Affiliated Huadu Hospital of Southern Medical University (People's Hospital of Huadu District), Guangzhou, Guangdong 510800, P.R. China, Department of Hepatopancreatobiliary Surgery, the Affiliated Hospital of Qinghai University, Xining, Qinghai 810001, P.R. China
    Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 799
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    Published online on: May 25, 2021
       https://doi.org/10.3892/etm.2021.10231
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Abstract

The aim of the present study was to explore the effect of exogenous hydrogen sulphide (H2S) on endoplasmic reticulum (ER) stress (ERS) in a rat model of hepatic ischemia/reperfusion (I/R) injury. A total of 48 Sprague‑Dawley rats were randomly divided into four groups (n=12/group) as follows: Sham, I/R, I/R preceded by NaHS (I/R‑NaHS) and I/R preceded by L‑C‑propargylglycine (PAG), a H2S inhibitor (I/R‑PAG). With the exception of the sham group, the rats in the other groups were subjected to 30 min hepatic warm ischemia followed by reperfusion for 6 or 12 h. Hepatic function was evaluated by serum concentrations of alanine aminotransferase (ALT). Apoptosis of hepatic cells was assessed by TUNEL staining and measurement of caspase‑12 expression. The expression levels of ERS‑associated proteins and mRNAs of pancreatic ER eukaryotic translation initiation factor‑2a kinase (PERK), activating transcription factor‑6 (ATF6), glucose‑regulated protein (GRP) 78, TNF‑receptor‑associated factor (TRAF)‑2, C/EBP homologous protein (CHOP) and caspase‑12 were also measured by western blotting and reverse transcription‑quantitative PCR. The serum concentrations of ALT in the I/R and I/R‑PAG groups were found to be significantly higher compared with those in the sham and I/R‑NaHS groups after 6 h of reperfusion; in addition, the ALT level returned to normal in the I/R group, while it increased further in the I/R‑PAG group after 12 h of reperfusion. A higher cell apoptosis rate was observed in the I/R and I/R‑PAG groups and the highest cell apoptosis rate was observed in the I/R‑PAG group; correspondingly, the expression of caspase‑12 was increased in the I/R and I/R‑PAG groups. H2S appeared to significantly attenuate hepatic I/R‑induced ERS response, as indicated by the decreased expression of ATF6, PERK, GRP78, TRAF2 and CHOP. Endogenous H2S may serve a hepatoprotective function after I/R, and inhibition of endogenous H2S results in aggravation of I/R damage. Exogenous H2S was shown to inhibit ERS‑related gene expression, leading to suppression of inflammatory reaction and improvement of I/R damage. Therefore, exogenous H2S has therapeutic potential to alleviate hepatic I/R injury.
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Copy and paste a formatted citation
Spandidos Publications style
Chen L, Ma K, Fan H, Wang X and Cao T: Exogenous hydrogen sulfide protects against hepatic ischemia/reperfusion injury by inhibiting endoplasmic reticulum stress and cell apoptosis. Exp Ther Med 22: 799, 2021.
APA
Chen, L., Ma, K., Fan, H., Wang, X., & Cao, T. (2021). Exogenous hydrogen sulfide protects against hepatic ischemia/reperfusion injury by inhibiting endoplasmic reticulum stress and cell apoptosis. Experimental and Therapeutic Medicine, 22, 799. https://doi.org/10.3892/etm.2021.10231
MLA
Chen, L., Ma, K., Fan, H., Wang, X., Cao, T."Exogenous hydrogen sulfide protects against hepatic ischemia/reperfusion injury by inhibiting endoplasmic reticulum stress and cell apoptosis". Experimental and Therapeutic Medicine 22.2 (2021): 799.
Chicago
Chen, L., Ma, K., Fan, H., Wang, X., Cao, T."Exogenous hydrogen sulfide protects against hepatic ischemia/reperfusion injury by inhibiting endoplasmic reticulum stress and cell apoptosis". Experimental and Therapeutic Medicine 22, no. 2 (2021): 799. https://doi.org/10.3892/etm.2021.10231
Copy and paste a formatted citation
x
Spandidos Publications style
Chen L, Ma K, Fan H, Wang X and Cao T: Exogenous hydrogen sulfide protects against hepatic ischemia/reperfusion injury by inhibiting endoplasmic reticulum stress and cell apoptosis. Exp Ther Med 22: 799, 2021.
APA
Chen, L., Ma, K., Fan, H., Wang, X., & Cao, T. (2021). Exogenous hydrogen sulfide protects against hepatic ischemia/reperfusion injury by inhibiting endoplasmic reticulum stress and cell apoptosis. Experimental and Therapeutic Medicine, 22, 799. https://doi.org/10.3892/etm.2021.10231
MLA
Chen, L., Ma, K., Fan, H., Wang, X., Cao, T."Exogenous hydrogen sulfide protects against hepatic ischemia/reperfusion injury by inhibiting endoplasmic reticulum stress and cell apoptosis". Experimental and Therapeutic Medicine 22.2 (2021): 799.
Chicago
Chen, L., Ma, K., Fan, H., Wang, X., Cao, T."Exogenous hydrogen sulfide protects against hepatic ischemia/reperfusion injury by inhibiting endoplasmic reticulum stress and cell apoptosis". Experimental and Therapeutic Medicine 22, no. 2 (2021): 799. https://doi.org/10.3892/etm.2021.10231
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