4-oxoretinol and retinol-acetate

The effects of large doses of preformed vitamin A, such as those provided in supplementation programs for the prevention of deficiency, on total serum vitamin A have been inadequately investigated.. This study characterized the time course of serum vitamin A metabolites in lactating sows after single high doses of retinyl ester.. Lactating sows were fitted with jugular catheters and subsequently fed either 1.05 or 2.1 mmol retinyl ester (n = 6/group) or a corn oil vehicle (n = 3). Blood was collected at baseline and at intervals to 48 h and analyzed by gradient HPLC for retinol, retinyl esters, and metabolites.. The mean (+/-SD) total serum vitamin A concentration peaked at 1 h (3.69 +/- 4.0 mumol/L) and 2 h (7.70 +/- 6.8 mumol/L) in the low- and high-dose groups, respectively (P < 0.05). Retinyl esters accounted for most of the serum vitamin A in both groups at peak time points. Mean serum retinol concentrations changed little and accounted for most of the serum vitamin A at baseline (94% and 97% for the low- and high-dose groups, respectively) but for only 22% and 14% at peak times for the low- and high-dose groups, respectively. Postdosage increases were observed for total vitamin A and retinyl esters, 4-oxoretinol, retinoyl beta-glucuronide, and retinyl beta-glucuronide but not for retinoic acid.. Serum retinol concentration remains relatively static after a large dose of preformed vitamin A and therefore is not an appropriate measure of intervention efficacy. The increases in beta-glucuronide metabolites and 4-oxoretinol suggest a preventive role against a rise in retinoic acid and retinol.

Topics: Animals; Diterpenes; Female; Glucuronides; Lactation; Retinyl Esters; Swine; Vitamin A

All-trans [11-3H]4,4- difluororetinyl acetate was synthesized by treating methyl all-trans [11-3H]4- oxoretinoate with diethylaminosulfurtrifluoride , followed by reduction and acetylation of the product. After oral administration of the radioactive difluoro analog in oil to rats, difluororetinol , difluororetinyl palmitate and related esters, 4- oxoretinol , 4- oxoretinoic acid and polar conjugated derivatives were identified in the intestine, liver, kidney and/or blood. The major metabolic products were difluororetinyl palmitate and related esters, which were stored in the liver. The presence of the difluoro analog in liver oil from treated rats was confirmed by 19F-NMR spectroscopy. Neither retinol nor retinyl esters were detected as products of the metabolism of the difluoro analog. Nonetheless, all-trans difluororetinyl acetate showed 26 +/- 12% of the biological activity of all-trans retinyl acetate in the rat growth assay. Presumably, the difluoro analog is active per se in growth rather than by conversion to retinol or to one of its known growth-promoting metabolites. In general, however, the difluoro analog was metabolized in a manner very similar to vitamin A. The vitamin A moiety of administered difluororetinyl acetate and retinyl acetate was poorly stored (1.8-3.3%) in the liver of vitamin A-depleted rats, confirming and extending past reports that the liver storage mechanism is severely impaired when initial liver stores are very low.

Topics: Animals; Biological Assay; Body Weight; Diterpenes; Feces; Kinetics; Liver; Magnetic Resonance Spectroscopy; Male; Rats; Rats, Inbred Strains; Retinyl Esters; Tissue Distribution; Tretinoin; Vitamin A