Beneficial effects of gaseous hydrogen sulfide in hepatic ischemia/reperfusion injury

Transpl Int. 2012 Aug;25(8):897-908. doi: 10.1111/j.1432-2277.2012.01514.x. Epub 2012 Jun 21.

Abstract

Hydrogen sulfide (H2 S) can induce a reversible hypometabolic state, which could protect against hypoxia. In this study we investigated whether H2 S could protect livers from ischemia/reperfusion injury (IRI). Male C57BL/6 mice were subjected to partial hepatic IRI for 60 min. Animals received 0 (IRI) or 100 ppm H2 S (IRI + H2 S) from 30 min prior to ischemia until 5 min before reperfusion. Core body temperature was maintained at 37° C. Animals were sacrificed after 1, 6 or 24 h. Hepatic ischemia caused extensive hepatic necrosis in the IRI animals which coincided with an increase in ALT and AST serum levels. Animals treated with H2 S showed attenuated serum ALT and AST levels and reduced necrotic lesions after 24 h. IRI animals had increased Bcl-2 mRNA expression and increased active Caspase 3 protein, which were both significantly lower in H2 S treated animals. Increased TNFα and IL-6 mRNA in the IRI livers was significantly attenuated by H2 S treatment, as was hepatic influx of Ly-6G positive granulocytes. Hepatic superoxide production after ischemia was attenuated by H2 S treatment. In hepatic ischemia/reperfusion injury, gaseous H2 S treatment is highly protective, substantially reducing necrosis, apoptosis and inflammation. Gaseous H2 S is therefore a very promising treatment for reducing IRI during hepatic transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine Transaminase / blood
  • Animals
  • Apoptosis / drug effects
  • Aspartate Aminotransferases / blood
  • Hydrogen Sulfide / pharmacology
  • Hydrogen Sulfide / therapeutic use*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / prevention & control*
  • Superoxides / metabolism

Substances

  • Superoxides
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Hydrogen Sulfide