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

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 degrees 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 H2S 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 TNFa 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.