Selective inhibition of fatty acid oxidation in colonocytes by ibuprofen: a cause of colitis?
Ibuprofen is associated with initiation or exacerbation of ulcerative colitis. As ibuprofen selectively inhibited fatty acid oxidation in the liver or caused mitochondrial damage in intestinal cells, its effect on substrate oxidation by isolated colonocytes of man and rat was examined. Ibuprofen dose dependently (2.0-7.5 mmol/l) and selectively inhibited 14CO2 production from labelled n-butyrate in colonocytes from the proximal and distal human colon (n = 12, p = < 0.001). Glucose oxidation was either unaltered or increased. Because short chain fatty acid oxidation is the main source of acetyl-CoA for long chain fatty acid synthesis, the inhibition of prostaglandin synthesis by ibuprofen in the colonic mucosa could also occur at this level. Because the concentrations of ibuprofen that can be attained in the human colon are not known, conclusions drawn from current dosages are tentative. The inhibition of fatty acid oxidation by ibuprofen may be biochemically implicated in the initiation and exacerbation of ulcerative colitis, manifestation of which would depend on the ibuprofen concentrations reached in the colon.
Roediger
W E
WE
Department of Surgery, Queen Elizabeth Hospital, Adelaide, Australia.
Millard
S
S
D000636:Aminosalicylic Acids / Q000494:pharmacology; D000818:Animals; D002087:Butyrates / Q000378:metabolism; D020148:Butyric Acid; D002245:Carbon Dioxide / Q000378:metabolism; D002478:Cells, Cultured; D003093:Colitis, Ulcerative / Q000139:chemically induced*; D003106:Colon / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007052:Ibuprofen / Q000009:adverse effects / Q000494:pharmacology*; D019804:Mesalamine; D010084:Oxidation-Reduction / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D000636:Aminosalicylic Acids; D002087:Butyrates; D005227:Fatty Acids; D020148:Butyric Acid; D002245:Carbon Dioxide; D019804:Mesalamine; D005947:Glucose; D007052:Ibuprofen