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Oxygen free radical-induced histamine release during intestinal ischemia and reperfusion
1Institute of Experimental Surgery, Szent-Györgyi Albert Medical University, Szeged, Hungary.
Abstract:
Acute mesenteric ischemia is highly lethal and therefore a serious problem for surgery and intensive care medicine; accordingly its pathophysiology warrants further study. Oxygen free radicals (OFR) play a role in the intestinal mucosal damage that develops during reperfusion after ischemia. Histamine (H) is generally released in various types of tissue ischemia. The link between H release and OFR has only been studied in in vitro systems. We tested the hypothesis that OFR may be involved in H release following reperfusion of the ischemic gut. The artery supplying a segment of the ileum was occluded for 1 or 2 h in anesthetized dogs. On reperfusion, a release of H into the venous effluent of the segment was demonstrated. Pretreatment of the animals with allopurinol (an inhibitor of xanthine oxidase), or with MTDQ-DA [6,6'-methylene-bis(2,2-dimethyl-4-methanesulfonic acid sodium-1,2-dihydroquinoline)], a superoxide anion scavenger, or with a combination of allopurinol and MTDQ-DA resulted in an inhibition of H release. We conclude that OFR may play a role in the local H release following intestinal ischemia.
Insights
Oxygen free radicals (OFR) contribute to histamine release during intestinal reperfusion after ischemia. Inhibiting OFR formation reduced histamine release, suggesting a therapeutic target for acute mesenteric ischemia.
Area of Science:
- Surgery
- Intensive Care Medicine
- Gastroenterology
- Pathophysiology
Background:
- Acute mesenteric ischemia is a life-threatening condition requiring further research into its pathophysiology.
- Oxygen free radicals (OFR) are implicated in intestinal mucosal damage during reperfusion injury.
- Histamine (H) release is observed in tissue ischemia, but its link to OFR is poorly understood in vivo.
Purpose of the Study:
- To investigate the role of oxygen free radicals (OFR) in histamine (H) release during intestinal reperfusion following acute mesenteric ischemia.
- To test the hypothesis that OFR mediate H release in the ischemic gut upon reperfusion.
Main Methods:
- Anesthetized dogs underwent temporary occlusion (1-2 hours) of the ileum artery to induce ischemia.
- Histamine levels were measured in the venous effluent during the reperfusion phase.
- Animals were pretreated with allopurinol (xanthine oxidase inhibitor) or MTDQ-DA (superoxide anion scavenger), or both, prior to reperfusion.
Main Results:
- Reperfusion of the ischemic ileum segment led to a significant release of histamine into the venous effluent.
- Pretreatment with allopurinol or MTDQ-DA, individually or in combination, markedly inhibited histamine release.
- These findings demonstrate a direct correlation between OFR activity and histamine release in this model.
Conclusions:
- Oxygen free radicals (OFR) play a significant role in the local histamine (H) release following intestinal ischemia and reperfusion.
- Targeting OFR pathways may offer a therapeutic strategy to mitigate histamine release and associated damage in acute mesenteric ischemia.
- Further research into the OFR-histamine axis is warranted for surgical and critical care interventions.