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 th e liver or caused mitochondrial damage in intestinal cells, its effect on substrate oxidation by isolated colonocytes of man and rat was exa mined. Ibuprofen dose dependently (2.0-7.5 mmol/l) and selectively inh ibited (CO2)-C-14 production from labelled n-butyrate in colonocytes f rom the proximal and distal human colon (n=12, p=<0.001). Glucose oxid ation was either unaltered or increased. Because short chain fatty aci d 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 concent rations of ibuprofen that can be attained in the human colon are not k nown, conclusions drawn from current dosages are tentative. The inhibi tion of fatty acid oxidation by ibuprofen may be biochemically implica ted in the initiation and exacerbation of ulcerative colitis, manifest ation of which would depend on the ibuprofen concentrations reached in the colon.