Studies on the in vivo metabolism of retinoic acid in the rat

Abstract

A time study of the metabolism of 6,7-¹⁴C-retinoic acid after intraperitoneal injection of physiological levels (17 μg, 0.39 μc) into vitamin A deficient rats, which had been repleted with retinoic acid for two weeks up to two days before injection, resulted in a rapid metabolism to more polar compounds in the small intestine and its contents and a slower metabolism to primarily different materials in the liver and kidney. The major route of metabolism resulted in the urinary excretion of 60% of the injected dose in 24 to 27 hr. Urinary metabolites of 15-¹⁴C-retinoic acid were eluted from silicic acid at a similar concentration of solvents as the ring labeled metabolites although only 32% of the injected dose was recovered in 24 hr. Compounds chromatographically similar to the urinary metabolites were observed at various times in the liver, kidney and small intestine plus contents in addition to retinoic acid and other metabolites. The relative amounts of the metabolites in the different tissues studied varied as a function of the tissue and the time of analysis after injection. Most of the radioactivity from all tissues was extractable into methanol. A liver subcellular distribution of the radioactivity derived from the intraperitoneal injection of 650 μg of 6,7-¹⁴C-retinoic acid (25.9 μc) after 3 hr indicated a minimal level of association of radioactivity (150–250 dpm/mg protein) with all fractions and a greater association of radioactivity with the lysosomal-microsomal fraction (300–350 dpm/mg protein) and the 60–100% ammonium sulfate precipitable (750–800 dpm/mg protein) and 100% ammonium sulfate soluble fractions (422 dpm/mg protein) of the soluble supernatant.