Hydrogen sulfide attenuates hepatic ischemia-reperfusion injury: role of antioxidant and antiapoptotic signaling

Am J Physiol Heart Circ Physiol. 2008 Aug;295(2):H801-6. doi: 10.1152/ajpheart.00377.2008. Epub 2008 Jun 20.


Hydrogen sulfide (H(2)S) is an endogenously produced gaseous signaling molecule with diverse physiological activity. The potential protective effects of H(2)S have not been evaluated in the liver. The purpose of the current study was to investigate if H(2)S could afford hepatoprotection in a murine model of hepatic ischemia-reperfusion (I/R) injury. Hepatic injury was achieved by subjecting mice to 60 min of ischemia followed by 5 h of reperfusion. H(2)S donor (IK1001) or vehicle were administered 5 min before reperfusion. H(2)S attenuated the elevation in serum alanine aminotransferase (ALT) by 68.6% and aspartate aminotransferase (AST) by 70.8% compared with vehicle group. H(2)S-mediated cytoprotection was associated with an improved balance between reduced glutathione (GSH) vs. oxidized glutathione (GSSG), an attenuated formation of lipid hydroperoxides, and an increased expression of thioredoxin-1 (Trx-1). Furthermore, H(2)S inhibited the progression of apoptosis after I/R injury by increasing the protein expression of heat shock protein (HSP-90) and Bcl-2. These results indicate that H(2)S protects the murine liver against I/R injury through an upregulation of intracellular antioxidant and antiapoptotic signaling pathways.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine Transaminase / blood
  • Animals
  • Antioxidants / metabolism
  • Antioxidants / pharmacology*
  • Apoptosis / drug effects*
  • Aspartate Aminotransferases / blood
  • Cytoprotection
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Glutathione / metabolism
  • Glutathione Disulfide / metabolism
  • HSP90 Heat-Shock Proteins / metabolism
  • Hydrogen Sulfide / metabolism*
  • Lipid Peroxidation / drug effects
  • Liver / blood supply
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Oxidative Stress / drug effects
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / pathology
  • Reperfusion Injury / prevention & control*
  • Signal Transduction / drug effects*
  • Sulfides / metabolism
  • Sulfides / pharmacology*
  • Thioredoxins / metabolism


  • Antioxidants
  • HSP90 Heat-Shock Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Sulfides
  • Txn1 protein, rat
  • Thioredoxins
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Glutathione
  • Glutathione Disulfide
  • sodium sulfide
  • Hydrogen Sulfide