title: Porcine intestinal metabolism of excess vitamin a differs following vitamin a supplementation and liver consumption.
abstract: Vitamin A is a well-established teratogen in all animal species. A number of case reports also suggest a teratogenic potential of vitamin A in humans. A possible teratogenic risk of dietary liver vitamin A intake, the kinetics of vitamin A and its metabolites in humans after intake of either a vitamin A supplement or a liver meal have been studied. Major differences were described for the kinetics of all-trans-retinoic acid (all-trans-RA), which occurred at much higher concentrations after supplementation than after liver consumption. Therefore, we investigated whether the intestine may be responsible for the differences in vitamin A metabolism after supplementation or liver feeding. We found that cytosolic fractions of porcine enterocytes oxidized retinol to all-trans-RA in vitro with a K(m) of 94-96 micromol/L and a V(max) of 7.9-8.6 pmol/(min x mg protein). In an in vivo approach, the portal vein and the central vein (external jugular vein) of a pig were cannulated. In two subsequent experiments, the pig was given a vitamin A supplement or liver. Plasma samples were taken from portal and central veins. Comparison of retinoid levels in these veins indicated that all-trans-RA was already formed from supplemental vitamin A in the intestine and released into the systemic circulation. Two major metabolic pathways were additionally present in the pig, leading to the formation of glucuronides of all-trans-RA and retinol itself. Our results indicate that intestinal metabolism contributes to the elevated levels of all-trans-RA in the systemic circulation after supplementation with vitamin A, but not after consumption of liver.
authors.affiliation: Department of Food Toxicology, School of Veterinary Medicine Hannover, D-30173 Hannover, Germany. thomas.arnhold@bc.boehringer-ingelheim.de
authors.forename: Thomas
authors.initials: T
authors.lastname: Arnhold
authors.forename: Heinz
authors.initials: H
authors.lastname: Nau
authors.forename: Silke
authors.initials: S
authors.lastname: Meyer
authors.forename: Hermann J
authors.initials: HJ
authors.lastname: Rothkoetter
authors.forename: Alfonso D
authors.initials: AD
authors.lastname: Lampen
mesh_terms: D000818:Animals; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D003600:Cytosol / Q000378:metabolism; D019587:Dietary Supplements; D020895:Enterocytes / Q000378:metabolism* / Q000648:ultrastructure; D007408:Intestinal Absorption; D007601:Jugular Veins; D008099:Liver / Q000737:chemistry*; D008861:Microsomes / Q000378:metabolism; D023421:Models, Animal; D010084:Oxidation-Reduction; D011169:Portal Vein; D012176:Retinoids / Q000097:blood*; D013552:Swine; D014212:Tretinoin / Q000097:blood / Q000493:pharmacokinetics*; D014801:Vitamin A / Q000008:administration & dosage / Q000378:metabolism*
chemical_list: D012176:Retinoids; D014801:Vitamin A; D014212:Tretinoin