Effects of 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin on vitamin A metabolism in mice

This study aimed to clarify the ef- fects of single and repeated administration of 2,3,7,8- tetrachlorodibenzo-p-dioxin (TCDD) on the activities or expression of some metabolic enzymes of retinoids and the influence of supplemental vitamin A on changed vitamin A homeostasis by TCDD. In Exper- iment I, the mice were given a single oral dose of 40 � g TCDD/kg body weight, with or without continuous ad- ministration of 2500 IU vitamin A/kg body weight/day, and were killed on day 1, 3, 7, 14, and 28. In Experiment II, the mice were daily given 0.1 � g TCDD/kg body weight, with or without supplemental 2000 IU vitamin A/kg body weight, and were killed on day 14, 28, and 42. In both experiments, TCDD significantly decreased the hepatic all-trans-retinol level and increased the hep- atic all-trans-retinoic acid (RA) content, increased the mRNA and enzymatic activities of retinal oxidase. In TCDD + vitamin A mice, the all-trans retinol con- tent was significantly higher, and the retinal oxidase mRNA was significantly lower on day 3 or 7 in Exper- iment I and on day 14 in Experiment II, compared to TCDD-treated mice. The induction of the retinal oxi- dase may contribute to the decrease in hepatic all-trans- retinol level and the increase in hepatic all-trans-RA caused by TCDD. Supplemental vitamin A might de- celerate the effect of TCDD on retinal oxidase mRNA. C