Induction of colitis in rats by 2-2'-azobis(2-amidinopropane) dihydrochloride.
Reactive oxygen metabolites (ROM) may play a role in the pathophysiology of inflammatory bowel disease (IBD) and ischemia-reperfusion-induced intestinal injury. Although there are many reports of intestinal mucosal injury associated with neutrophil-derived ROM, free radicals themselves have not been reported to induce intestinal mucosal injury. We administered intrarectally 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) to rats, an azo compound that generates free radicals in vitro. Acute mucosal injury was assessed histologically by light microscopy and biochemically by myeloperoxidase (MPO) activity. Intrarectal administration of AAPH (60, 90, 150 mg/kg) caused erythema, edema, and histologically verifiable mucosal inflammation. MPO activity was increased 9- to 18-fold above the control level. The levels of thiobarbituric acid (TBA) reactants and sulfhydryls (SH) were significantly (P less than 0.01) increased and decreased, respectively, by 90 mg/kg AAPH. Sulfasalazine, 5-aminosalicylic acid, the LTB4 receptor antagonist SC-41930, and the antioxidant glutathione prevented the inflammation. This model of mucosal inflammation may be useful in evaluating new therapeutic agents for the treatment of IBD.
Gastrointestinal Diseases Research, Searle Research and Development, Skokie, Illinois 60077.
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D000578:Amidines; D000636:Aminosalicylic Acids / Q000494:pharmacology*; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D003092:Colitis / Q000139:chemically induced*; D007249:Inflammation / Q000139:chemically induced; D007413:Intestinal Mucosa / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D019804:Mesalamine; D010084:Oxidation-Reduction; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012460:Sulfasalazine / Q000494:pharmacology*; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013858:Thiobarbiturates / Q000378:metabolism
D000578:Amidines; D000636:Aminosalicylic Acids; D001578:Benzopyrans; D013438:Sulfhydryl Compounds; D013858:Thiobarbiturates; C059950:SC 41930; D012460:Sulfasalazine; D019804:Mesalamine; C046728:2,2'-azobis(2-amidinopropane); D009195:Peroxidase; C029684:thiobarbituric acid