Hydrogen Sulfide Confers Protection Against Hepatic Warm Ischemia Reperfusion Injury in Mice

Introduction: Hydrogen sulfide (H2S) reduces ischemia and reperfusion injury (IRI) in some organs including liver, however, the precise mechanism of protection remains elusive. The present study was designed to assess whether H2S derivative (Sodium hydrogen sulfide; NaHS) reduced hepatic IRI, and to elucidate the mechanisms of protection. Methods: Mice were subjected to 70% partial warm ischemia for 75 min and followed by reperfusion. Ten minutes before reperfusion, either NaHS (1mg/kg) or saline was intravenously administered. Sham operation was also performed. Animals were sacrificed at 6 hours after reperfusion (n=6). Serum ALT activity, HE staining, and tissue lipid peroxidation (LPO) products were assessed. Signal transduction pathways of survival, apoptosis, and autophagy were evaluated by western blot (n=4); phospho-mTOR, phospho-AMPK alpha, LC3B, phospho-Akt, cleaved-caspase3, p-Bad, and beta-actin. Results: The NaHS treatment suppressed hepatic IRI shown by significantly less ALT release, LPO products, and vacuolization in HE staining.Figure: [HE staining of liver]Figure: [ALT and Lipid Peroxidation]Seven-day survival was 67% (4/6)and 100% (6/6) non-treatment and NaHS groups, respectively (N.S.). The NaHS treatment significantly augmented the level of phospho-mTOR, tended to augment that of phospho-Akt and phospho-AMPK alpha, and tended to reduce that of cleaved-Caspase3, as compared to the non-treatment group.Figure: [Results of Western Blot]Conclusion: Sodium hydrogen sulfide reduced hepatic warm ischemia and reperfusion injury in mice. The modification of pro-survival/anti-apoptotic and autophagy related signal, together with antioxidant property was considered as the possible mechanisms of protection.