Gastric mucosal injury in the rat. Role of iron and xanthine oxidase.
Recent studies have implicated oxygen free radicals in ischemia-reperfusion injury to the gastric mucosa. The aims of the present study were to test the hypothesis that the enzyme xanthine oxidase is the source of the oxygen radicals in the ischemic stomach and determine the importance of the iron-catalyzed Haber-Weiss reaction in generating the cytotoxic oxygen radicals. Gastric mucosal clearance of 51Cr-labeled red blood cells was measured during a 30-min control period, a 30-min ischemic period (hemorrhage to 25 mmHg arterial pressure), and a 60-80-min reperfusion period (reinfusion of shed blood). In untreated (control) rats, a dramatic rise (100-fold) in the leakage of 51Cr-labeled red blood cells into the gastric lumen was observed only during the reperfusion period. After the reperfusion period, gastric mucosal damage was further assessed using gross lesion area and histology. Rats were placed on a sodium tungstate diet (to inactivate xanthine oxidase), or treated with either deferoxamine (an iron chelating agent) or superoxide dismutase (a superoxide scavenger). All three interventions substantially reduced 51Cr-labeled red blood cell clearance and gross lesion area relative to untreated rats. However, tissue injury assessed histologically was similar in both treated and untreated animals. The results of this study support the hypothesis that oxygen free radicals mediate the hemorrhagic shock-induced extravasation of red blood cells. The data also indicate that xanthine oxidase is the source of the oxy-radicals and that the iron-catalyzed Haber-Weiss reaction is largely responsible for hydroxyl radical generation in this model.
D000818:Animals; D002860:Chromium Radioisotopes; D003676:Deferoxamine / Q000494:pharmacology; D004912:Erythrocytes / Q000502:physiology; D005609:Free Radicals; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D007501:Iron / Q000378:metabolism*; D007511:Ischemia / Q000378:metabolism; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013482:Superoxide Dismutase / Q000494:pharmacology; D013997:Time Factors; D014414:Tungsten / Q000494:pharmacology; D017973:Tungsten Compounds; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors / Q000378:metabolism*
D002860:Chromium Radioisotopes; D005609:Free Radicals; D017973:Tungsten Compounds; C025399:sodium tungstate(VI); D007501:Iron; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase; D003676:Deferoxamine; D014414:Tungsten