Effect of acetylsalicylic acid on fatty acid omega-hydroxylation in rat liver.
The effect of acetylsalicylic acid on the cytochrome P-450-mediated fatty acid omega-hydroxylation system was assessed in male Sprague-Dawley rats after they were fed a diet containing 1% (w/w) acetylsalicylic acid. A 3-fold increase in the specific activity of laurate omega-hydroxylation was observed in the acetylsalicylic acid fed rats in comparison to control rats. This effect of acetylsalicylic acid was unique as the specific activities of other cytochrome P-450-mediated reactions were not increased. The induction of the laurate omega-hydroxylation system was also manifested in a rapid formation of its dicarboxylic acid derivative, dodecanedioic acid, as the omega-hydroxy derivative was further oxidized by alcohol and aldehyde dehydrogenases. These results suggest the acetylsalicylic acid is similar to other peroxisomal proliferating agents in that it also induces the microsomal fatty acid omega-hydroxylation system and may account for the appearance of unique dicarboxylic acids in Reye's syndrome patients.
D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003998:Dicarboxylic Acids / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D006900:Hydroxylation; D007850:Lauric Acids / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008830:Microbodies / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D003998:Dicarboxylic Acids; D005227:Fatty Acids; D007850:Lauric Acids; C030358:lauric acid; D003577:Cytochrome P-450 Enzyme System; C036836:dodecanedioic acid; D001241:Aspirin