Effect of phorone and allopurinol on ischemia-reperfusion injury in gastrointestinal mucosa of the rat.
We studied the effect of inhibition of oxyradical formation and of endogenous glutathione (GSH) depletion on lesion formation in the gastrointestinal tract in a modified rat hemorrhagic shock model (1 h hypotension and 1 h reperfusion). Allopurinol, an inhibitor of xanthine oxidase, did not protect against lesion formation. This suggests that oxygen radicals generated from xanthine oxidase may not be the major cause of injury under these conditions of prolonged 'ischemia'-reperfusion. Phorone (diisopropylideneacetone), a GSH depletor, decreased mucosal GSH levels in the corpus, duodenum and small intestine, and also significantly reduced lesion formation histologically in the corpus, antrum, duodenum and small intestine. However, there was no significant differences in mucosal blood flow (as estimated by changes in mucosal hemoglobin concentrations and oxygen saturation of mucosal hemoglobin) in the corpus, antrum, duodenum and small intestine between phorone-pretreated and control rats. We conclude that phorone decreased mucosal GSH concentrations and exerted a protective effect against hemorrhagic shock-induced gastrointestinal mucosal lesions. The protective effect appears to be independent of mucosal blood flow.
Yasue
N
N
Research Service, Veterans Administration Medical Center West Los Angeles, Calif.
Chan
E T
ET
Kaplowitz
N
N
Guth
P H
PH
D000493:Allopurinol / Q000494:pharmacology*; D000818:Animals; D004386:Duodenum / Q000187:drug effects; D005609:Free Radicals; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D007413:Intestinal Mucosa / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D007421:Intestine, Small / Q000187:drug effects; D007659:Ketones / Q000494:pharmacology*; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow / Q000187:drug effects; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D012771:Shock, Hemorrhagic / Q000150:complications
D005609:Free Radicals; D007659:Ketones; D000493:Allopurinol; C018637:phorone; D005978:Glutathione