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Hydrogen sulfide alleviates ischemia induced liver injury by repressing the SPHK1/S1P pathway.
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ABSTRACT: Background
Ischemia/reperfusion (I/R) induced liver injury is a severe pathological process which frequently occurs during clinical hepatic operations. The current study investigated the protective function and underlying mechanisms of hydrogen sulfide (H2S) in I/R induced liver injury.Methods
The effects of H2S were examined using the fibroblast-like rat liver cell line BRL-3A (the name of normal hepatocytes in rats) cultured under hypoxic conditions and an I/R rat model. The viability of BRL-3A cells was assessed using the methylthiazolyldiphenyl-tetrazolium (MTT) assay and Hoechst analysis. The expression of C/EBP homologous protein (CHOP), sphingosine kinase 1 (SPHK1), and sphingosine 1-phosphate (S1P) were determined in hypoxic BRL-3A cells with or without H2S treatment. CHOP was overexpressed in hypoxic BRL-3A cells to further evaluate whether H2S protected the liver against I/R injury by decreasing endoplasmic reticulum (ER) stress. Finally, the inflammation levels in the serum and the histopathological changes of liver were examined in the I/R rat model to evaluate the therapeutic function of H2S on I/R induced liver injury in vivo.Results
H2S alleviated hypoxic damage in BRL-3A cells. In addition, hypoxia increased the expression of CHOP, SPHK1, and S1P in BRL-3A cells, and this was abolished by H2S pretreatment. Notably, overexpression of CHOP significantly inhibited the effect of H2S on the viability of BRL-3A cells during hypoxia. Overall, H2S effectively protected against I/R induced liver injury, decreased the inflammatory responses, and attenuated apoptosis of hepatocyte via inhibiting the ER stress response.Conclusions
These findings demonstrated that pre-treatment of H2S protected against I/R induced liver injury by repressing the SPHK1/S1P pathway via inhibition of ER stress, suggesting an effective therapeutic method for the treatment of I/R induced liver injury.
SUBMITTER: Chen L
PROVIDER: S-EPMC9929751 | biostudies-literature | 2023 Jan
REPOSITORIES: biostudies-literature
Publications
Hydrogen sulfide alleviates ischemia induced liver injury by repressing the SPHK1/S1P pathway.
Annals of translational medicine 20230101 2
<h4>Background</h4>Ischemia/reperfusion (I/R) induced liver injury is a severe pathological process which frequently occurs during clinical hepatic operations. The current study investigated the protective function and underlying mechanisms of hydrogen sulfide (H<sub>2</sub>S) in I/R induced liver injury.<h4>Methods</h4>The effects of H<sub>2</sub>S were examined using the fibroblast-like rat liver cell line BRL-3A (the name of normal hepatocytes in rats) cultured under hypoxic conditions and an ...[more]