The function of vitamin A: current concepts.
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Animals↗
Biomedical subjects
M H Zile
Publications and source records attributed to M H Zile.
Metabolites of all-trans-retinoic acid in bile: identification of all-trans- and 13-cis-retinoyl glucuronides.
The metabolites of all-trans-[3H]retinoic acid were studied in the rat bile. In the bile duct cannulated rat 80 to 86% of the dose is excreted into the bile within 24 h after the intravenous administration of either a physiological or pharmacological dose of all-trans-[3H]retinoic acid. Polar metabolites of retinoic acid predominate (73 to 96% of bile 3H) in the bile at all times; some free retinoic acid (0.2 to 4.8% of bile 3H) is excreted into the bile during the initial 6-h period after dosing. Retinoyl glucuronides are excreted into the bile for 12 h after dosing; their excretion is highest during the first 2 h. More retinoyl glucuronide is excreted from the pharmacological dose (10% of the radiolabel dose) than the physiological dose (4.4% of the dose) of all-trans-retinoic acid. The retinoyl glucuronides were separated and were shown to consist of all-trans- and 13-cis-retinoyl glucuronides in a ratio of 1.5 to 1.0. Since the starting material was 99% all-trans-retinoic acid and the methods used do not cause isomerization, it is concluded that cis-trans isomerization of retinoic acid is a physiologically relevant reaction.
Animals↗
Metabolism in vivo of all-trans-retinoic acid. Biosynthesis of 13-cis-retinoic acid and all-trans- and 13-cis-retinoyl glucuronides in the intestinal mucosa of the rat.
The metabolites of all-trans-[3H]retinoic acid appearing in the intestines of bile duct-cannulated rats were compared to those of similarly treated intact rats. 2.4% of administered radioactivity was found in the small intestines of bile duct-cannulated rats 2 H after dose, while a much larger proportion of the dose (7.2%) was found in the intestines of the intact rats. All-trans- and 3-cis-retinoic acids predominate in the intestinal mucosa of bile duct-cannulated rats shortly after dosing. Retinoyl glucuronide was the major metabolite occurring as a mixture of the all-trans and 13-cis forms. Highly polar metabolites of retinoic acid appear in mucosa at all times in both intact and bile duct-cannulated rats demonstrating rapid metabolism of retinoic acid in intestine. The finding of a similar proportion of the 13-cis isomers in retinoic acids and retinoyl glucuronides suggests that injected all-trans-retinoic acid is isomerized in vivo probably prior to conjugated with glucuronic acid.
Animals↗
DNA labeling of rat epithelial tissues in vitamin A deficiency.
We examined the effect of vitamin A nutritional status on cell division in various epithelial tissues of the rat. Tissues were examined by histological methods, and DNA labeling was assessed by autoradiography. Mild vitamin A deficiency decreased the DNA labeling index in the trachea and the epidermis, while not altering the histological appearance of the tissue. In some tracheae, foci of hyperplasia were present. The histological appearance and the DNA labeling index of the cornea, jejunum and colon were not altered by mild vitamin A deficiency. We concluded that a diminished proliferation of epithelial cells is a manifestation of suboptimal vitamin A availability in that tissue.
Animals↗
Characterization of retinoyl beta-glucuronide as a minor metabolite of retinoic acid in bile.
Several metabolites detected in the bile of rats given radioactive retinoic acid were separated by liquid/gel partition chromatography and purified by high-pressure liquid chromatography. One of these metabolites was found to be sensitive to beta-D-glucuronidase, yielding both 13-cis- and all-trans-retinoic acid. It had the characteristic ultraviolet absorption spectrum of retinoic acid esters. Trimethylsilyl ether and acetyl derivatives of the methylated metabolite were prepared and examined by mass spectrometry. The resulting mass spectra established the structure to be retinoyl beta-glucuronide. Retinoyl glucuronide was rapidly excreted into the bile: the excretion was complete by 12 hr after the administration of retinoic acid. At this time the metabolite represented 12% of bile radioactivity (10% of dose). These observations confirm the existence of retinoyl glucuronide but demonstrate that it represents only one of several retinoic acid metabolites in bile.
Animals↗
The biological activity of 5,6-epoxyretinoic acid.
The potential of all-trans-5,6-epoxyretinoic acid to promote growth in vitamin A-deficient rats was evaluated over a 25-fold dose range using single daily intraperitoneal injections. 5,6-Epoxyretinoic acid was found to be 0.5% as active as all-trans-retinoic acid. The discrepancies between the present results and those obtained previously by other workers are discussed.
Administration, Oral↗
On the physiological basis of vitamin A-stimulated growth.
The influence of vitamin A depletion on tissue composition was studied in rats that were marginally vitamin A deficient, i.e. at their weight plateau stage. The total number of cells (DNA) was decreased in most organs as a result of vitamin A depletion. In thymus, spleen and the sublingual glands there was also a dramatic reduction in the number of cells per gram of tissue and in thymus and sublingual glands there was an increase in the protein to DNA ratio as a result of absence of dietary.vitamin A. We present the hypothesis that vitamin A stimulates growth by a direct role in cell replication in addition to or instead of stimulating the differentiation of epithelial and bone cells.
Animals↗
Identification of 13-cis retinoic acid in tissue extracts and its biological activity in rats.
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Animals↗