Association of cytochrome P450 induction with oxidative stress in vivo as evidenced by 3-hydroxylation of salicylate

1. Previous studies have shown that formation of 2,3-dihydroxybenzoate (2,3-DHB) from salicylate in vivo is a sensitive and specific marker of. OH radical generation, since 2,3-DHB is formed exclusively by. OH radicals, whereas both. OH radicals and cytochrome P450 (CYP) contribute to the production of 2,5-DHB. In the present study the salicylate-hydroxylation assay was used to examine whether CYP induction by the administration of dexamethasone, phenobarbital or β-naphthoflavone to the male rat led to oxidative stress in vivo. 2. Dexamethasone was used under conditions that induced an ~50-fold induction of CYP P4503A expression in liver microsomal protein. Treatment with dexamethasone caused a 17.2-fold increase in 2,3-DHB plasma concentration compared with control animals. An increase in total hydroxylated salicylate (2,3-DHB plus 2,5-DHB) of 133.5 μmol/l plasma was produced, of which - assuming that the attack by. OH in position 3 or 5 of salicylate occurs at a similar rate - 10.9 μmol/l were due to. O...