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

Abstract

Hydrogen sulfide (H2S) can induce a reversible hypometabolic state, which could protect against hypoxia. In this study we investigated whether H2S 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 H2S (IRI + H2S) 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 H 2S 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 H2S treated animals. Increased TNFα and IL-6 mRNA in the IRI livers was significantly attenuated by H2S treatment, as was hepatic influx of Ly-6G positive granulocytes. Hepatic superoxide production after ischemia was attenuated by H2S treatment. In hepatic ischemia/reperfusion injury, gaseous H2S treatment is highly protective, substantially reducing necrosis, apoptosis and inflammation. Gaseous H2S is therefore a very promising treatment for reducing IRI during hepatic transplantation. © 2012 European Society for Organ Transplantation.