Metabolism, Plasma Transport and Biliary Excretion of Radioactive Vitamin A and its Metabolites as a Function of Liver Reserves of Vitamin A in the Rat

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Abstract
Groups of 7–12 weanling Sprague-Dawley male rats were fed graded daily doses of vitamin A (5–176 µg retinol) for 7 or 12 weeks. Final mean liver concentrations of vitamin A, which ranged from 0.4 to 331 µg retinol per gram, depended both on the daily dose given and on the length of the feeding period. The mean serum retinol concentration was 24 µg/dl at the lowest liver vitamin A concentration, approached a plateau of 40 µg/dl at a liver concentration of 5–10 µg/g, and then very slowly increased with higher levels of vitamin A in the liver. Seven days after the oral administration of a standard dose (4.6 µCi) of 11,12-[3H2]retinyl acetate, during which period rats were fed the customary vitamin A-containing diet, bile was collected via bile duct cannulae for 1–4 hours, and then the livers and serum were extracted and analyzed. The key relationships defined were: 1) that the mean ratio of specific activities of retinol in serum to that in liver was 0.65 ± 0.05 (SEM) (range: 0.46–0.81) at daily retinol intakes of 8–176 µg/day, 2) that the ratio did not vary systematically with vitamin A intake or liver reserves and 3) that the mean excretion rate of vitamin A metabolites in the bile was invariant at 0.28 µg retinol metabolites per milliliter of bile up to a liver vitamin A concentration of 32 µg retinol per gram, but then increased rapidly by eightfold to a maximal rate of 2.4 µg retinol metabolites per milliliter of bile at a liver vitamin A value of 140 µg retinol per gram. These observations are helpful both in selecting methods of evaluating vitamin A status as well as in understanding the effect of varying liver stores on the metabolism and excretion of vitamin A.