Hydrogen sulfide protects rat lung from ischemia-reperfusion injury.
Recent studies have indicated that hydrogen sulfide (H(2)S) is capable of modulating many physiological processes, which prompted us to investigate the potential of H(2)S as a lung protective agent. To explore changes in the generation of endogenous H(2)S and the role of H(2)S in the pathogenesis of pulmonary ischemia-reperfusion (I/R) injury in rats, we built an isolated rat lung I/R model. Lungs were subjected to 45 min ischemia followed by reperfusion (45 min) and were pretreated with H(2)S (50 micromol/l or 100 micromol/l) or an irreversible inhibitor of cystathionine-gamma-lyase (CSE), propargylglycine (PPG; 2 mmol/l). We examined indices of lung injury: lung histological change, perfusion flow rate, ratio of lung wet weight to dry weight (w/d), and lung compliance. H(2)S content and CSE protein expression in lung tissues were measured. Malondialdehyde (MDA) content, activities of superoxide dismutase (SOD) and catalase (CAT), and restraint of superoxide anion (O(2)(-)) production in lung tissues were measured to reflect oxidative stress. In the current study, we demonstrated that H(2)S content and CSE activity in lungs after I/R were significantly higher than those in the control group. Preperfusion with H(2)S attenuated the lung I/R injury while preperfusion with PPG aggravated the lung I/R injury. H(2)S preperfusion reduced I/R-induced MDA production and potentiated SOD and CAT activities and the restraint of O(2)(-) production in the lungs under I/R, which attenuated lung oxidative injury. These findings suggest that endogenous CSE/H(2)S pathway might be involved in the pathogenesis of lung I/R injury and that administration of H(2)S might be of clinical benefit in lung I/R injury.
Fu
Zhifang
Z
Department of Geriatrics, Peking University First Hospital, Xishiku Street No. 8, West District, Beijing, 100034, Beijing, People's Republic of China.
Liu
Xinmin
X
Geng
Bin
B
Fang
Liping
L
Tang
Chaoshu
C
D000818:Animals; D003542:Cystathionine gamma-Lyase / Q000096:biosynthesis; D005609:Free Radicals / Q000378:metabolism; D006862:Hydrogen Sulfide / Q000378:metabolism / Q000627:therapeutic use*; D066298:In Vitro Techniques; D008168:Lung / Q000098:blood supply / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008170:Lung Compliance / Q000187:drug effects; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000201:enzymology / Q000378:metabolism / Q000517:prevention & control*
D005609:Free Radicals; D003542:Cystathionine gamma-Lyase; D006862:Hydrogen Sulfide