Role of Hydrogen Sulfide in Severe Burn Injury-Induced Inflammation in Mice

Endogenous hydrogen sulfide (H2S) is naturally synthesized in many types of mammalian cells from L-cysteine in the reactions catalyzed by cystathionine-beta-synthase and cystathionine-gamma-lyase (CSE) H2S has been demonstrated to play a proinflammatory role in various animal models of hindpaw edema, acute pancreatitis, lipopolysaccharide-induced endotoxemia and cecal ligation, and puncture-induced sepsis. Full-thickness burns that exceed 25% of the total body surface area (TBSA) produce a profound systemic inflammatory reaction characterized by leukocyte activation and plasma leakage in the microvasculature of tissues and organs remote from the wound. The aim of this study was to investigate the effect of local burn injury on induced distant organ endogenous H2S release and expression of CSE Male BALB/c mice were subjected to 30% TBSA full-thickness burn and treated with saline (administered intraperitoneally (i p)); DL-propargylglycine (PAG, 50 mg/kg i p). which is a CSE inhibitor, or sodium hydrosulfide (NaHS, 10 mg/kg i.p.), which is an H2S donor. PAG was administered either 1 h before or 1 h after the burn injury, whereas NaHS was given at the same time as the burn injury Measurements of liver myeloperoxidase (MPO) activities, liver H2S-synthesizing activity, plasma H2S level and liver and lung CSE mRNA expression and histological examination of tissues were performed offer burn injury. Burn injury significantly increased the plasma H2S level and liver H2S synthesis 8 h after burn compared with the sham group. Burn injury also resulted in a significant upregulation of CSE mRNA in liver and lung. Prophylactic as well as therapeutic administration of PAG significantly reduced burn-associated systemic inflammation, as evidenced by MPO activity and histological changes in liver and lung. Injection of NaHS significantly aggravated burn-associated systemic inflammation Therefore, our findings show for the first time the role of H2S in contributing to inflammatory damage after burn injury (C) 2010 The Feinstein Institute for Medical Research, www.feinsteininstitute.org