title: Chronic vitamin A status and acute repletion with retinyl palmitate are determinants of the distribution and catabolism of all-trans-retinoic acid in rats.
abstract: The relation between vitamin A (VA) nutritional status and the metabolism of all-trans-retinoic acid (RA) is not well understood. In this study, we determined the tissue distribution and metabolism of a test dose of [(3)H]-RA in rats with graded, diet-dependent, differences in VA status. The design included 3 groups, designated VA-deficient, VA-marginal, and VA-adequate, with liver total retinol concentrations of 9.7, 35.7 and 359 nmol/g, respectively, (P < 0.05), and an additional group of VA-deficient rats treated with a single oral dose of retinyl palmitate (RP) 20 h before the injection of [(3)H]-RA. Plasma, liver, lung, and small intestines, collected 30 min after [(3)H]-RA, were analyzed for total (3)H, unmetabolized [(3)H]-RA, polar organic-phase metabolites of [(3)H]-RA, and aqueous phase [(3)H]-labeled metabolites. In all groups, [(3)H]-RA was rapidly removed from plasma and concentrated in the liver. VA deficiency did not prevent the oxidative metabolism of RA. Nevertheless, the quantity of [(3)H]-RA metabolites in plasma and the ratio of total [(3)H]-polar metabolites to unmetabolized [(3)H]-RA in liver varied directly with VA status (VA-adequate > VA-marginal > VA-deficient, P < 0.05). Moreover, supplementation of VA-deficient rats with RP reduced the metabolism of [(3)H]-RA, similar to that in VA-adequate or VA-marginal rats. Liver retinol concentration, considered a proxy for VA status, was correlated (P < 0.05) with [(3)H]-RA metabolites in liver (R(2) = 0.54), plasma (R(2) = 0.44), lung (R(2) = 0.40), intestine (R(2) = 0.62), and all combined (R(2) = 0.655). Overall, the results demonstrate close linkage between dietary VA intake, hepatic storage of VA, and the degradation of RA and suggest that measuring plasma retinoid metabolites after a dose of RA may provide insight into the metabolism of this bioactive retinoid by visceral organs.
authors.affiliation: Department of Nutritional Sciences, The Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Cifelli
authors.forename: A Catharine
authors.initials: AC
authors.lastname: Ross
mesh_terms: D000818:Animals; D001835:Body Weight; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D004224:Diterpenes; D005260:Female; D009929:Organ Size; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D000072516:Retinoic Acid 4-Hydroxylase; D000084562:Retinyl Esters; D014212:Tretinoin / Q000378:metabolism*; D014801:Vitamin A / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D004224:Diterpenes; D012333:RNA, Messenger; D000084562:Retinyl Esters; D014801:Vitamin A; C014794:retinol palmitate; D014212:Tretinoin; D003577:Cytochrome P-450 Enzyme System; D000072516:Retinoic Acid 4-Hydroxylase