Diethylmaleate, a pro-oxidant, attenuates experimental ischaemia-reperfusion-induced lung injury.
BACKGROUND
Systemic ischaemia-reperfusion (IR) injury is in part an oxidant injury mediated by neutrophils. Diethylmaleate (DEM), an intracellular pro-oxidant agent, has been shown to alleviate neutrophil-mediated tissue injury. The aim of this study was to evaluate whether DEM could have a protective effect on neutrophil-mediated lung injury in an animal model of lower-torso IR.


METHODS
Sprague-Dawley rats (seven per group) were randomized into three groups. The control group underwent midline laparotomy only; the IR group underwent laparotomy and clamping of the infrarenal abdominal aorta for 30 min followed by 2 h of reperfusion; and the third group was pretreated with DEM 6 mmol/kg intraperitoneally 1 h before the IR insult.


RESULTS
IR resulted in a significant increase in both microvascular leakage and pulmonary neutrophil infiltration as measured by bronchoalveolar lavage protein concentration and pulmonary myeloperoxidase activity respectively. Pretreatment with DEM significantly attenuated both microvascular leakage and neutrophil infiltration.


CONCLUSIONS
Preconditioning with DEM protected against IR-induced lung injury. This protective effect raises the possibility of using pro-oxidants to prevent inflammatory injury.
Kiely
P D
PD
Department of Surgery, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin, Ireland. PaulKiely@amnch.ie
Wang
J C
JC
Kelly
C J
CJ
Condron
C
C
Watson
R G K
RG
Bouchier-Hayes
D J
DJ
D000818:Animals; D001011:Aorta; D003250:Constriction; D008168:Lung / Q000098:blood supply; D008171:Lung Diseases / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D008298:Maleates / Q000627:therapeutic use*; D008833:Microcirculation; D009504:Neutrophils; D016877:Oxidants / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*
D008298:Maleates; D016877:Oxidants; C014476:diethyl maleate