Vol. 27, Issue 3, 317-321, March 1999

Metabolism of Retinaldehyde Isomers in Pregnant Rats: 13-cis- and all-trans-Retinaldehyde, but not 9-cis-Retinaldehyde, Yield Very Similar Patterns of Retinoid Metabolites

Jörn Oliver Sass, Georg Tzimas, Mohamed M.A. Elmazar, and Heinz Nau

Universitätsklinik für Kinder- und Jugendheilkunde, Stoffwechsellabor, Innsbruck, Austria (J.O.S.); Tzimas-Dimolios Co., Thessaloniki, Greece (G.T.); King Saud University, College of Pharmacy, Riyadh, Saudi Arabia (M.M.A.E.); AND Tierärztliche Hochschule Hannover, Zentrumsabteilung für Lebensmitteltoxikologie, Hannover, Germany (H.N.)

Retinaldehyde (RAL), a key intermediate in retinoid metabolism, acts as a retinoic acid (RA) precursor, but is also reduced to retinol (ROH), which can subsequently be esterified to retinyl esters, the storage form of vitamin A. Limited information is available on the metabolism of geometric isomers of RAL as well as on the transplacental distribution of their metabolites, including RA isomers. Such information would be very helpful for the assessment of the teratogenic potency of RAL isomers, as teratogenesis represents a major side effect of retinoid use in pharmacotherapy. In the present study we examined concentrations of retinoids in plasma, maternal tissues, and embryos of pregnant rats 2 h after a single oral dose (100 mg/kg body weight) of all-trans-, 13-cis-, or 9-cis-RAL on gestational day 13. The main findings of this study were the very similar patterns of retinoid metabolites (consisting of retinoids with mainly the all-trans-configuration) after administration of all-trans- and 13-cis-RAL, and the high concentrations of 9-cis-RA, 9,13-dicis-RA, and 9-cis-retinoyl--D-glucuronide after dosing with 9-cis-RAL. In addition, all-trans-RA as a RAL metabolite reached the embryos to a much greater extent than any of its cis-isomers. The results are discussed in view of in vitro data on enzymes involved in the biotransformation of RAL isomers.