Metabolic induction of experimental ulcerative colitis by inhibition of fatty acid oxidation.
There is some evidence that failure of fatty acid or beta-oxidation in the epithelium of the colonic mucosa is associated with the development of ulcerative colitis. We tested the hypothesis that inhibition of fatty acid oxidation in the colonic mucosa of the rat reproduces the histological, clinical and biochemical lesions of acute ulcerative colitis of man. A specific inhibitor of beta-oxidation, sodium 2-bromo-octanoate, was instilled rectally for 5 days or exposed to isolated colonic epithelial cells which were subsequently tested for their ability to beta-oxidize n-butyrate. Weight loss, bloody diarrhoea and histological lesions occurred with 2-bromo-octanoate treated rats but not control animals. Ketogenesis and 14CO2 production was inhibited by 2-bromo-octanoate. Of 12 animals mucosal ulceration developed in six out of eight surviving animals and in all four animals that died. Ulceration, mucus cell depletion, vessel dilatation and increases of inflammatory cells were the most prominent histological changes. Present observations indicate that inhibition of beta-oxidation produces acute colitis and suggests that inhibition of beta-oxidation is primary rather than secondary in the genesis of ulcerative colitis. A search for agents producing such biochemical lesions in man should be undertaken.
D000818:Animals; D000975:Antioxidants; D001835:Body Weight / Q000187:drug effects; D002210:Caprylates; D002245:Carbon Dioxide / Q000378:metabolism; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D003106:Colon / Q000378:metabolism* / Q000473:pathology; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D007413:Intestinal Mucosa / Q000378:metabolism; D007657:Ketone Bodies / Q000096:biosynthesis; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D000975:Antioxidants; D002210:Caprylates; D005227:Fatty Acids; D007657:Ketone Bodies; D002245:Carbon Dioxide; C019279:2-bromooctanoic acid