Role of phospholipase A2 and oxygenated free radicals in mucosal damage after small intestinal ischemia and reperfusion.
The influence of quinacrine, a phospholipase A2 inhibitor, and enzymatic scavengers of active oxygen metabolites (superoxide dismutase and catalase) on ischemic small intestinal mucosal damage has been investigated. In the absence of an inhibitor, ischemia and reperfusion caused increased mucosal permeability to sodium fluorescein, increased N-acetyl-glucosaminidase release from the mucosa into the lumen, increased malondialdehyde content, and increased myeloperoxidase and phospholipase A2 (PLA2) activities in the mucosa. All these effects of ischemia were efficiently inhibited by the PLA2 inhibitor quinacrine. On the other hand, superoxide dismutase together with catalase, even if it totally prevented the increased formation of malondialdehyde, was only able to reduce 50 percent of the increases of the other parameters. These findings indicate that, in addition to free radicals, other factors are involved in the pathogenesis of small intestinal mucosal injury after ischemia and reperfusion. We suggest that one such factor is the activation of PLA2 and the generation of various PLA2-dependent compounds such as arachidonic acid metabolites, lysophosphatidyl choline, and platelet-activating factor.
Otamiri
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Clinical Research Center, University Hospital, Linköping, Sweden.
Tagesson
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C
D000118:Acetylglucosaminidase / Q000378:metabolism; D000818:Animals; D002374:Catalase / Q000494:pharmacology; D005609:Free Radicals; D007082:Ileum / Q000098:blood supply*; D007413:Intestinal Mucosa / Q000201:enzymology*; D007511:Ischemia / Q000201:enzymology / Q000378:metabolism*; D008315:Malondialdehyde / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D010539:Permeability; D009195:Peroxidase / Q000378:metabolism; D010740:Phospholipases / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D011796:Quinacrine / Q000494:pharmacology; D051381:Rats; D015424:Reperfusion; D013482:Superoxide Dismutase / Q000494:pharmacology
D005609:Free Radicals; D008315:Malondialdehyde; D002374:Catalase; D009195:Peroxidase; D013482:Superoxide Dismutase; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2; D000118:Acetylglucosaminidase; D011796:Quinacrine; D010100:Oxygen