vitamin-a2 and 3-4-didehydroretinoic-acid

This study demonstrates early embryonic metabolism of exogenous all-trans-3,4-didehydroretinol (vitamin A2) to all-trans-3,4-didehydroretinal and to all-trans-3,4-didehydroretinoic acid in Xenopus embryos during neurulation. The latter metabolite was recently shown to bind with high affinity and to activate various retinoic acid receptors. Embryos treated with all-trans-3,4-didehydroretinol during early or late gastrulation exhibited abnormalities along the anteroposterior axis. The abnormalities were primarily in the posterior regions of the embryo, with only minor defects anteriorally. Eye malformations, typical for early exposure to 9-cis- and all-trans-retinols and retinals (companion paper), were not observed. We also present evidence that all-trans-3,4-didehydroretinoic acid is present endogenously during early neurulation and is evenly distributed along the anteroposterior axis. After treatment with all-trans-3,4-didehydroretinol, embryonic levels of all-trans-3,4-didehydroretinoic acid exceeded endogenous levels of this metabolite during early and late neurulation. We hypothesize that the dysmorphogenic effects produced by treatment of Xenopus embryos with the alcohol precursor, all-trans-3,4-didehydroretinol, are the result of its embryonic conversion to its corresponding acid ligand.

Topics: Abnormalities, Drug-Induced; Animals; Chromatography, High Pressure Liquid; Embryo, Nonmammalian; Female; Phenotype; Teratogens; Tretinoin; Vitamin A; Xenopus laevis

The modified relative-dose-response (MRDR) assay has been validated in rats as a function of vitamin A status and tested in a group of American children. In this study the MRDR assay was applied to West Javan children who are at risk of being vitamin A deficient. Of 86 children enrolled, 75 were tested. In a time-course study involving 22 children aged 3.7-5.3 y, blood samples were taken at different times after doses of 0.35 mumol 3,4-didehydroretinyl acetate/kg body wt. Generally, the ratio of dehydroretinol to retinol (DR-R ratio) peaked between 4 and 8 h. Thereafter, in a survey of 53 children aged 0.6-4.8 y, single blood samples were drawn 5 h after the dehydroretinyl acetate dose. The DR-R ratio ranged from 0.0028 to 0.169. With a DR-R ratio of 0.03 as the cutoff value, 62% of the children were judged to be of marginal vitamin A status.

Topics: Anthropometry; Child, Preschool; Dose-Response Relationship, Drug; Humans; Indonesia; Infant; Nutritional Status; Time Factors; Tretinoin; Vitamin A; Vitamin A Deficiency

The relative-dose-response (RDR) assay first proposed by Underwood has proved to be a useful indicator of marginal vitamin A status. We suggested that 3,4-didehydroretinol might be used in a simpler assay that requires only one blood sample for analysis. In the present study 24 healthy children aged 3.7-7.1 y were given 100 micrograms 3,4-didehydroretinyl acetate/kg body wt in corn oil, followed by ice cream (90 mL). A blood sample was taken 2, 4, 5, 6, 8, 10, or 24 h after the dose. The mean ratio of dehydroretinol to retinaol (DR-R ratio) plateaued at approximately 0.02 in the plasma between 4 and 10 h. Only three children showed ratios greater than 0.03. Upon reinvestigation, the DR-R ratio remained greater than 0.03 in one child at 5 h. After vitamin A treatment the ratio decreased to 0.019. Thus, a tentative DR-R cutoff ratio for a satisfactory vitamin A status in healthy American children is 0.03.

Topics: Child; Child, Preschool; Dose-Response Relationship, Drug; Female; Humans; Iowa; Male; Nutritional Status; Reference Values; Tretinoin; Vitamin A