Ritchie Helen E, Brown-Woodman Patricia D, Korabelnikoff Ann
School of Biomedical Sciences, University of Sydney, Cumberland Campus, Lidcombe, NSW, Australia.
Birth Defects Res A Clin Mol Teratol. 2003 Jun;67(6):444-51. doi: 10.1002/bdra.10054.
Excess retinyl palmitate (vitamin A) induces a variety of malformations in many mammalian species, yet retinyl palmitate is not thought to be the proximate teratogen. Many metabolites are generated after oral dosing several of which are, individually teratogenic. It is not known whether these metabolites when present simultaneously interact in an additive or synergistic manner.
Whole rat embryos were cultured with retinol, all-trans retinoic acid (tRA), 4-oxo all-trans retinoic acid (4otRA) or 9-cis retinoic acid (9cRA). Retinoids were added singly or in paired combinations at the start of culture and embryos were examined for evidence of dysmorphogenesis at the end of culture. Retinoids were added at both subthreshold and supra-threshold concentrations.
Co-administration of subthreshold concentrations of tRA and 4otRA, retinol and tRA or 4otRA and 4otRA and 9cRA resulted in a greater frequency of abnormal embryos compared to single administration of each retinoid.
Knowledge of the way in which retinyl palmitate metabolites interact should refine our ability to predict risk from a potentially teratogenic event e.g., accidental overdose with RP during human pregnancy.
过量的棕榈酸视黄酯（维生素A）在许多哺乳动物物种中会诱发多种畸形，但棕榈酸视黄酯不被认为是直接的致畸原。口服给药后会产生许多代谢产物，其中一些单独就具有致畸性。尚不清楚这些代谢产物同时存在时是否会以相加或协同的方式相互作用。
将大鼠全胚胎与视黄醇、全反式维甲酸（tRA）、4-氧代全反式维甲酸（4otRA）或9-顺式维甲酸（9cRA）一起培养。在培养开始时单独或成对添加类视黄醇，培养结束时检查胚胎是否有畸形发生的迹象。以低于阈值和高于阈值的浓度添加类视黄醇。
与单独给予每种类视黄醇相比，同时给予低于阈值浓度的tRA和4otRA、视黄醇和tRA或4otRA和4otRA以及9cRA会导致异常胚胎的发生率更高。
了解棕榈酸视黄酯代谢产物的相互作用方式，应能提高我们预测潜在致畸事件（例如人类怀孕期间意外过量摄入RP）风险的能力。
