Effects of cyclooxygenase and lipoxygenase inhibition on eicosanoids and healing of acetic acid colitis in rats.
Both cyclooxygenase products, such as prostaglandin (PG) E2, and lipoxygenase products, such as leukotriene (LT) B4, are increased in colitis and have potent proinflammatory actions. We studied effects of specific inhibitors of cyclooxygenase and 5-lipoxygenase on the healing of acetic acid colitis in rats. Acetic acid colitis was induced 24 hr before enzyme inhibition began. Four days after induction of colitis, the area of gross colonic mucosal damage was determined by image analysis. Eicosanoid content in the intestinal lumen was quantitated by radioimmunoassay following chromatographic purification. Under these conditions, indomethacin significantly retarded the healing of colonic lesions and inhibited PGE2 by > 90% compared to placebo-treated colitis rats. AA861 had no effect on the healing of lesions, although > 75% inhibition of leukotriene synthesis was demonstrated. These results suggest that inhibition of endogenous colonic prostaglandins can impair healing mechanisms in acute colitis even after inflammation has developed. In contrast, inhibition of leukotriene synthesis did not affect healing.
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Department of Medicine, Harbor UCLA Medical Center, Torrance.
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Guth
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Reedy
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D000085:Acetates; D019342:Acetic Acid; D000704:Analysis of Variance; D000818:Animals; D016227:Benzoquinones / Q000008:administration & dosage; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003106:Colon / Q000187:drug effects / Q000473:pathology; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D015777:Eicosanoids / Q000032:analysis / Q000378:metabolism*; D007213:Indomethacin / Q000008:administration & dosage; D016859:Lipoxygenase Inhibitors / Q000627:therapeutic use*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014945:Wound Healing / Q000187:drug effects*
D000085:Acetates; D016227:Benzoquinones; D016861:Cyclooxygenase Inhibitors; D015777:Eicosanoids; D016859:Lipoxygenase Inhibitors; C036837:2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone; D019342:Acetic Acid; D007213:Indomethacin