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

J Biochem Mol Toxicol. 2005;19(5):327-35. doi: 10.1002/jbt.20097.

Abstract

This study aimed to clarify the effects 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 Experiment I, the mice were given a single oral dose of 40 mug TCDD/kg body weight, with or without continuous administration of 2,500 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 microg TCDD/kg body weight, with or without supplemental 2,000 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 hepatic all-trans-retinoic acid (RA) content, increased the mRNA and enzymatic activities of retinal oxidase. In TCDD + vitamin A mice, the all-trans retinol content was significantly higher, and the retinal oxidase mRNA was significantly lower on day 3 or 7 in Experiment I and on day 14 in Experiment II, compared to TCDD-treated mice. The induction of the retinal oxidase 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 decelerate the effect of TCDD on retinal oxidase mRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyltransferases / genetics
  • Alcohol Dehydrogenase
  • Aldehyde Oxidase
  • Aldehyde Oxidoreductases / genetics
  • Animals
  • Chromatography, High Pressure Liquid
  • Homeostasis
  • Liver / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Oxidation-Reduction
  • Polychlorinated Dibenzodioxins / toxicity*
  • Polymerase Chain Reaction
  • RNA, Messenger / genetics
  • Tretinoin / blood
  • Tretinoin / metabolism
  • Vitamin A / blood
  • Vitamin A / metabolism*

Substances

  • Polychlorinated Dibenzodioxins
  • RNA, Messenger
  • Vitamin A
  • Tretinoin
  • Alcohol Dehydrogenase
  • Aldehyde Oxidoreductases
  • Aldehyde Oxidase
  • Aox1 protein, mouse
  • Acyltransferases
  • lecithin-retinol acyltransferase