Effect of tetrachlorodibenzo-p-dioxin (TCDD) on the glucuronidation of retinoic acid in the rat

Biochim Biophys Acta. 1989 Oct 13;993(1):1-6. doi: 10.1016/0304-4165(89)90134-7.

Abstract

Administration of a single oral dose (10 micrograms/kg) of tetrachlorodibenzo-p-dioxin (TCDD) caused a 33% decrease in retinyl esters in the livers of male rats, but a 13-fold increase in retinyl esters in the kidney and a 3-fold increase in serum retinol. Liver and kidney microsomal uridine diphosphoglucuronosyltransferase (UDPGT) activity toward all-trans-retinoic acid was increased 3.7- and 2.6-fold, respectively, ten days following exposure to TCDD. Verification of the in vitro formation of [3H]retinoyl beta-glucuronide (RG) was by cochromatography with authenic RG on reversed phase high pressure liquid chromatography (HPLC), identification of retinoic acid as the hydrolysis product after beta-glucuronidase treatment, and the characterization of the all-trans-retinoyl glucuronide by negative fragment mass spectroscopy, fast atom bobardment. We conclude that increased retinoic acid glucuronidation may be a contributing factor to the hepatic depletion of vitamin A and the increased excretion of vitamin A metabolites following TCDD exposure.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Chromatography, High Pressure Liquid
  • Dioxins / pharmacology*
  • Glucuronosyltransferase / metabolism*
  • Kidney / drug effects
  • Kidney / metabolism*
  • Kinetics
  • Liver / drug effects
  • Liver / metabolism*
  • Male
  • Mass Spectrometry
  • Microsomes, Liver / metabolism*
  • Polychlorinated Dibenzodioxins / pharmacology*
  • Rats
  • Rats, Inbred Strains
  • Reference Values
  • Tretinoin / analogs & derivatives*
  • Tretinoin / metabolism*
  • Vitamin A / isolation & purification
  • Vitamin A / metabolism*
  • Vitamin A Deficiency / metabolism

Substances

  • Dioxins
  • Polychlorinated Dibenzodioxins
  • Vitamin A
  • retinoyl glucuronide
  • Tretinoin
  • Glucuronosyltransferase