Wew. Roediger et S. Millard, SELECTIVE-INHIBITION OF FATTY-ACID OXIDATION IN COLONOCYTES BY IBUPROFEN - A CAUSE OF COLITIS, Gut, 36(1), 1995, pp. 55-59
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.