BACKGROUND: Lung injury induced by ischemia or reperfusion significantly accounts for the risk of early mortality of lung transplantation (LT). Recent studies have demonstrated that hydrogen sulfide (H2S) and its endogenous synthase cystathionine-γ-lyase (CSE) confer protection against injury induced by ischemia or reperfusion in various organs. This prompted us to define the role of CSE/H2S pathway in transplantation-induced lung injury. METHODS: We performed single left LT in male Sprague-Dawley rats after 3 h of cold ischemia time. H2S donor NaHS (14 μmol/kg, intraperitoneally) or CSE inhibitor propargylglycine (37.5 mg/kg, intraperitoneally) was administered 15 min before the start of the LT. CSE protein expression, H2S generation, and the severity of pulmonary graft injuries were estimated at 24 h after reperfusion. RESULTS: Both CSE protein expression and H2S generation were markedly decreased in transplanted rat lungs compared with those in sham-operated lungs. In the lung-transplanted rats, NaHS administration significantly improved pulmonary function and decreased lipid peroxidation and myeloperoxidase activity. In addition, NaHS inhibited the production of interleukin 1β but increased interleukin 10 levels in graft lung tissues. In contrast, propargylglycine further exacerbated pulmonary function and lung injuries after experimental orthotopic LT. CONCLUSIONS: To our knowledge, this study for the first time has demonstrated that the suppression of CSE expression and H2S production is associated with transplantation-induced lung injury. Both exogenous and endogenous H2S seem to have protective effects against acute LT injury by their multiple functions including antioxidation and anti-inflammation, suggesting that modulation of H2S levels may be considered a potential therapeutic approach in LT.
BACKGROUND:Lung injury induced by ischemia or reperfusion significantly accounts for the risk of early mortality of lung transplantation (LT). Recent studies have demonstrated that hydrogen sulfide (H2S) and its endogenous synthase cystathionine-γ-lyase (CSE) confer protection against injury induced by ischemia or reperfusion in various organs. This prompted us to define the role of CSE/H2S pathway in transplantation-induced lung injury. METHODS: We performed single left LT in male Sprague-Dawley rats after 3 h of cold ischemia time. H2SdonorNaHS (14 μmol/kg, intraperitoneally) or CSE inhibitor propargylglycine (37.5 mg/kg, intraperitoneally) was administered 15 min before the start of the LT. CSE protein expression, H2S generation, and the severity of pulmonary graft injuries were estimated at 24 h after reperfusion. RESULTS: Both CSE protein expression and H2S generation were markedly decreased in transplanted rat lungs compared with those in sham-operated lungs. In the lung-transplanted rats, NaHS administration significantly improved pulmonary function and decreased lipid peroxidation and myeloperoxidase activity. In addition, NaHS inhibited the production of interleukin 1β but increased interleukin 10 levels in graft lung tissues. In contrast, propargylglycine further exacerbated pulmonary function and lung injuries after experimental orthotopic LT. CONCLUSIONS: To our knowledge, this study for the first time has demonstrated that the suppression of CSE expression and H2S production is associated with transplantation-induced lung injury. Both exogenous and endogenous H2S seem to have protective effects against acute LT injury by their multiple functions including antioxidation and anti-inflammation, suggesting that modulation of H2S levels may be considered a potential therapeutic approach in LT.
Authors: Katalin Módis; Eelke M Bos; Enrico Calzia; Harry van Goor; Ciro Coletta; Andreas Papapetropoulos; Mark R Hellmich; Peter Radermacher; Frédéric Bouillaud; Csaba Szabo Journal: Br J Pharmacol Date: 2014-04 Impact factor: 8.739
Authors: Oscar McCook; Peter Radermacher; Chiara Volani; Pierre Asfar; Anita Ignatius; Julia Kemmler; Peter Möller; Csaba Szabó; Matthew Whiteman; Mark E Wood; Rui Wang; Michael Georgieff; Ulrich Wachter Journal: Nitric Oxide Date: 2014-03-18 Impact factor: 4.427
Authors: Kyle L Flannigan; Terence A Agbor; Rory W Blackler; Janice J Kim; Waliul I Khan; Elena F Verdu; Jose G P Ferraz; John L Wallace Journal: Proc Natl Acad Sci U S A Date: 2014-09-03 Impact factor: 11.205