Abstract
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.
Keywords
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Article info
Publication history
Published online: October 08, 2012
Accepted:
September 19,
2012
Received in revised form:
September 17,
2012
Received:
July 19,
2012
Identification
Copyright
© 2013 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
