Effect of Acetylsalicylic Acid on Fatty Acid ω-Hydroxylation in Rat Liver

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Abstract
The effect of acetylsalicylic acid on the cytochrome P-450-mediated fatty acid ω-hydroxylation system was assessed in male Sprague-Dawley rats after they were fed a diet containing 1% (w/w) acetylsa licylic acid. A 3-fold increase in the specific activity of laurate co-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 ω-hydroxylation system was also manifested in a rapid formation of its dicarboxylic acid derivative, dodecanedioic acid, as the ω-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 ω-hydroxylation system and may account for the appearance of unique dicarboxylic acids in Reye's syndrome patients.