Retinoic acid: some aspects of growth-promoting activity in the albino rat.
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Animals↗
Biomedical subjects
M Zile
Publications and source records attributed to M Zile.
Formation of retinoic acid from retinol in the rat.
1. The formation in vivo of retinoic acid from microgram quantities of intrajugularly administered [15-(14)C]retinol was demonstrated in the rat. 2. Endogenously formed retinoic acid (about 0.1mug./rat) was found in liver, and to a much smaller extent in intestine, 12hr. after retinol administration. 3. Excretion of some of the endogenously formed retinoic acid occurred in the bile of bile-duct-cannulated rats. 4. Excretion of unaltered retinoic acid in the urine of intact rats did not occur even after the intrajugular administration of preformed retinoic acid.
Animals↗
A biologically active metabolite of retinoic acid from rat liver.
1. Four major radioactive fractions have been isolated from the livers of vitamin A-deficient rats given [6,7-(14)C(2)]retinoic acid. 2. At least one of these was more potent than retinoic acid and approximately equal to retinol in the growth assay for vitamin A activity. 3. The biologically active material was chromatographically distinct from retinoic acid, retinol and retinal. 4. Alkaline hydrolysis of this material yielded an acidic compound containing all the radioactivity. 5. The methyl ester of the acidic product was unlike the methyl ester of retinoic acid in its chromatographic behaviour. 6. It is suggested that this metabolite may represent the active form of retinol in its growth-supporting role.
Journal Article↗
Aspects of teratology of vitamin A acid (beta-all-trans retinoic acid).
Retinoic acid must now be considered a normal metabolite of vitamin A. In fact, evidence now exists which can well support the idea that retinoic acid may itself be- or may be converted to-a metabolically active form which would carry out the growth-promoting functions of vitamin A. In contrast to retinol, retinoic acid is rapidly metabolized,being totally degraded within 48 hours after its adminstration to vitamin A-defiecient rats. Its primary excretory route is through the bile, the resulting metabolite retaining its intact side chain. At least one metabolite going through this excretory route has been identified as retinoyl-beta-glucuronide. However, retinoic acid undergoes oxidative decarboxylation of the terminal carbon to the extent of approximately 20%. Another 20% undergoes further degradation to lose the C-14. New chromatographic procedures as well as new extraction procedures which are gentle and give 100% recoveries have been described, which may be an important new tool in the elucidation of the metabolism of retinoic acid and retinol. So far at least eight metabolites of retinoic acid have been detected with these methods. However, none of these metabolites has yet been identified and their biological significance remains unknown.
Abnormalities, Drug-Induced↗