A COMPARlTlVE STUDY ON THE IN VlTRO HEPATIC METABOLISM OF RETlNOlC ACID USING DIFFERENT SPECIES

All trans retinoic acid (RA), derived from the oxidative metabolism of dietary retinol (vitamin A) and β carotene, contributes to the growth and differentiation of mammalian epithelial tissues. RA is rapidly cleared from the plasma and sudenly metabolized in tissues. The increase of its biological potency through inhibition of its oxidative metabolism is consistent with this.This research is part of a study to develop novel compounds as inhibitors of retinoic acid metabolism that could have potential value as anticancer agent. The investigation was done to compare the in vitro metabolism of [³H]RA by hepatic m icrosomes from several common laboratory animal species. Also, the ability of ketaconazole to inhibit RA metabolism was examined. The species studied were male rat, male New Zealand white rabbit, male albino mouse, male Syrian hamster, male Dunkin hartley guinea pig and male nude mouse. The results revealed that km and Vmax were species dependent. Among the animals, rat liver appeared to be the most active in metabolizing RA. Inhibition of RA metbolism by ketoconazole (100 µM) was very similar in the hepatic microsomes of all the species examine. Overall the results indicate that male rat hepatic microsomes represent a useful enzyme source for screening novel compounds as inhibitors of RA metabolism.