Metabolism of 5,6-epoxyretinoic acid in vivo: isolation of a major intestinal metabolite

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Abstract
The major metabolite in the small intestinal mucosa of vitamin A deficient rats dosed intrajugularly with 5,6-epoxy[3H]retinoic acid was identified as 5,6-epoxyretinoyl .beta.-glucuronide. The assignment was based on the metabolite''s chemical, spectral and chromatographic properties. Incubation of the metabolite with .beta.-glucuronidase released 5,6-epoxyretinoic acid. Incubation of 5,6-epoxyretinoic acid with rat liver microsomes in the presence of uridine-5''-diphospho-1.sbd.D-glucuronic acid produced the metabolite. 5,6-Epoxy[3H]retinoyl .beta.-glucuronide was observed in the liver, small intestinal mucosa, and intestinal contents but not in kidney of vitamin A deficient rats. Its concentration was greatly diminished in liver and small intestinal mucosa, and it was not observed in kidney of vitamin A deficient rats dosed orally with retinoic acid for several days before administration of 5,6-epoxy[3H]retinoic acid. Generally, oral retinoic acid treatment accelerated 5,6-epoxyretinoic acid metabolism and enhanced accumulation of highly polar metabolites. Moreover, 5,6-epoxyretinoic acid metabolism was more rapid than that of retinoic acid and did not result in production of retinoic acid.