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

Dig Dis Sci. 2017 Dec;62(12):3479-3486. doi: 10.1007/s10620-017-4811-8. Epub 2017 Oct 30.

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.

Keywords: ER stress; Hydrogen-rich saline; Ischemia-reperfusion; Oxidative stress.

Publication types

  • Evaluation Study

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Endoplasmic Reticulum Stress / drug effects*
  • Hepatic Insufficiency / prevention & control*
  • Hydrogen / pharmacology
  • Hydrogen / therapeutic use*
  • Liver / metabolism
  • Male
  • Malondialdehyde / metabolism
  • Random Allocation
  • Rats, Sprague-Dawley
  • Reperfusion Injury / prevention & control*
  • Sodium Chloride / pharmacology
  • Sodium Chloride / therapeutic use*
  • Superoxide Dismutase / metabolism

Substances

  • Sodium Chloride
  • Malondialdehyde
  • Hydrogen
  • Superoxide Dismutase