Toxicity, metabolism and applied uses of 3,4-didehydroretinol

Abstract

<p>The comparative potencies of the all-trans isomers of 3,4-didehydroretinyl acetate (A2), retinyl acetate (A1), and retinoic acid (RA) to induce terata, embryolethality, and behavioral disruptions in offspring of timed-pregnant Sprague-Dawley rats was evaluated. Single equimolar doses (1-352 [mu]mol/kg BW) of the retinoids were given orally in corn oil on day 8.5 of gestation. All retinoids tested were teratogenic and embryolethal at dose ranges of 35-352 [mu]mol/kg BW. Embryolethality also occurred with both A2 and RA at 11 [mu]mol/kg BW. Biochemical profiles of both maternal and fetal tissue indicated that increased teratogenicity and embryolethality in A2 dosed groups correlated with enhanced concentration of maternal and fetal RA. Both RA and A2 were more toxic and teratogenic than A1, possibly due to differences in transport and metabolism;Development and spontaneous motor behavior of six-week old pups from retinoid dosed dams were also evaluated. Live birth rates were reduced in groups receiving A2, though no external abnormalities were observed, regardless of the treatment received. Control and treated pups were paired and tested using a computer pattern recognition system (RAPID). Significant changes in motor behavior patterns were evident in males whose dams were dosed with 3.5 [mu]mol A2/kg BW and in females whose dams received 1 [mu]mol A2/kg BW. No significant behavioral effects were seen in males in either the A1 or RA groups;The vitamin A status of low-income pregnant women (n = 57) during the third trimester of pregnancy was assessed by use of A2 in the modified relative dose response (MRDR) assay. Non-Hispanic White (45), Hispanic (6), Afro-American (5), and Asian (1) women were recruited from public health programs in central Iowa. Twenty six percent of the study population were found to be in a marginal vitamin A status with MRDR values ≥0.03, whereas 9% had values ≥0.06. The Hispanic and Afro-American groups seemed to be most at risk, with 50% and 40% (respectively) of the MRDR values ≥0.03 and 33% and 20% (respectively) ≥0.06. Clearly, this study identifies a portion of the U.S. population at high risk of vitamin A inadequacy.</p>