Chronic vitamin A status and acute repletion with retinyl palmitate are determinants of the distribution and catabolism of all-trans-retinoic acid in rats

Christopher J. Cifelli, A. Catharine Ross

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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 [ 3H]-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 [3H]-RA. Plasma, liver, lung, and small intestines, collected 30 min after [3H]-RA, were analyzed for total 3H, unmetabolized [3H]-RA, polar organic-phase metabolites of [3H]-RA, and aqueous phase [3H]-labeled metabolites. In all groups, [3H]-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 [3H]-RA metabolites in plasma and the ratio of total [3H]-polar metabolites to unmetabolized [3H]-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 [ 3H]-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 [3H]-RA metabolites in liver (R2 = 0.54), plasma (R2 = 0.44), lung (R2 = 0.40), intestine (R 2 = 0.62), and all combined (R2 = 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.

Original languageEnglish (US)
Pages (from-to)63-70
Number of pages8
JournalJournal of Nutrition
Volume137
Issue number1
Publication statusPublished - Jan 1 2007

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All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

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