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Updated: Jul 18, 2026
A Rat Lung Transplantation Model of Warm Ischemia/Reperfusion Injury: Optimizations to Improve Outcomes
Published on: October 28, 2021
Diethylmaleate, a pro-oxidant, attenuates experimental ischaemia-reperfusion-induced lung injury
P D Kiely1, J C Wang, C J Kelly
1Department of Surgery, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin, Ireland. PaulKiely@amnch.ie
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.
Conclusion:
Preconditioning with DEM protected against IR-induced lung injury. This protective effect raises the possibility of using pro-oxidants to prevent inflammatory injury.
Insights
Diethylmaleate (DEM), a pro-oxidant, protected against ischemia-reperfusion (IR) lung injury by reducing neutrophil infiltration and microvascular leakage. This suggests pro-oxidants may prevent inflammatory damage.
Area of Science:
- Biomedical research
- Inflammatory response
- Oxidative stress
Background:
- Systemic ischemia-reperfusion (IR) injury involves oxidant damage mediated by neutrophils.
- Diethylmaleate (DEM), an intracellular pro-oxidant, can reduce neutrophil-mediated tissue damage.
Purpose of the Study:
- To investigate the protective effects of DEM against neutrophil-mediated lung injury in a lower-torso IR animal model.
Main Methods:
- Rats were divided into control, IR, and DEM-pretreated groups.
- The IR group experienced aortic clamping for 30 minutes followed by 2 hours of reperfusion.
- DEM (6 mmol/kg) was administered intraperitoneally 1 hour before the IR insult.
Main Results:
- Ischemia-reperfusion significantly increased microvascular leakage and pulmonary neutrophil infiltration.
- DEM pretreatment markedly reduced both microvascular leakage and neutrophil infiltration in the lungs.
Conclusions:
- Preconditioning with DEM effectively protected against ischemia-reperfusion-induced lung injury.
- These findings indicate that pro-oxidants could be utilized to prevent inflammatory injuries.
