Hydrogen-Rich Saline Ameliorates Hepatic Ischemia-Reperfusion Injury Through Regulation of Endoplasmic Reticulum Stress and Apoptosis

Abstract

Objective

To evaluate the effect of hydrogen-rich saline (HS) on hepatic ischemia-reperfusion (I/R) injury.

Methods

Forty rats were randomly allocated into five groups: one sham group (control group), one group treated with 20 min of ischemia and normal saline (NS; I/R1 + NS group), one group treated with 20 min of ischemia and HS (I/R1 + HS group), one group treated with 60 min of ischemia and NS (I/R2 + NS group), and one group treated with 60 min of ischemia and HS (I/R2 + HS group). After reperfusion for 6 h, hepatic function, oxidative stress, pathological changes, and apoptosis of hepatic cells were evaluated. Furthermore, the expression levels of endoplasmic reticulum (ER) stress-associated proteins were identified.

Results

Serum ALT and AST levels and tissue MDA content in the I/R + HS groups were significantly lower than those in the I/R + NS groups. Pathological changes were also significantly ameliorated in the HS groups compared with those in the NS groups. Moreover, HS appeared to significantly attenuate hepatic I/R-induced ER stress responses, as indicated by the decreased expression of C/EBP homologous protein, protein-kinase-RNA-like ER kinase, and inositol-requiring protein-1α, as well as the increased expression of GRP78 proteins. Finally, the levels of apoptotic markers such as caspase-3 and TUNEL-positive cells were significantly lower in the HS groups than in the NS control groups, whereas the level of Bcl2 protein increased in the HS groups.

Conclusion

The protective effect of HS can be attributed to ER stress and apoptosis inhibition.

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Acknowledgments

This work was supported by funding from Scientific Research Foundation for the Returned Overseas Chinese Scholars (No. 2014-1685) and National Undergraduate Innovative Research Projects of China (No. 201510559010).

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Correspondence to Jin Gong.

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Lu, Z., Lin, Y., Peng, B. et al. Hydrogen-Rich Saline Ameliorates Hepatic Ischemia-Reperfusion Injury Through Regulation of Endoplasmic Reticulum Stress and Apoptosis. Dig Dis Sci 62, 3479–3486 (2017). https://doi.org/10.1007/s10620-017-4811-8

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Keywords

  • Hydrogen-rich saline
  • Oxidative stress
  • Ischemia-reperfusion
  • ER stress