Chronic Vitamin A Status and Acute Repletion with Retinyl Palmitate Are Determinants of the Distribution and Catabolism of All-trans-retinoic Acid in Rats

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.