Effects of vitamin E on dolichol content of rats acutely treated with 1,2-dichloroethane

Toxicology. 2000 Mar 7;143(3):283-92. doi: 10.1016/s0300-483x(99)00181-x.

Abstract

Previous investigations have demonstrated that 1,2-dichloroethane (DCE) poisoning affects dolichol (Dol) concentration in rat liver. Dol, a long-chain polyprenol, is considered an important membrane component: as dolichyl phosphate, it is rate limiting for the synthesis of glycoprotein; as free or fatty acid, it is highly concentrated in the Golgi apparatus (GA) where it can increase membrane fluidity and permeability, required glycoprotein maturation and secretion. DCE biotransformation may stimulate pro-oxidant events through hepatocellular glutathione depletion. Since the molecules of Dol are susceptible to oxidative degradation, the aim of this investigation is to verify whether vitamin E (vit. E) supplementation in rats is able to prevent Dol breakdown during acute DCE treatment. Before acute DCE administration (628 mg/kg body weight), a group of male Wistar rats were pretreated with vit. E (33 mg/kg body weight) for 3 days. High-performance liquid chromatography analysis has shown that within 5-60 min after DCE administration, the Dol concentration decreased in liver homogenate, cytosol, microsomes and GA. Particularly, 60 min after the treatment, Dol levels in the trans Golgi fraction were 71% lower than in controls. Rat pre-treatment with vit. E prevented the DCE-induced decrease in Dol concentrations of all liver fractions considered, in particular the reduction of total-Dol observed in the trans Golgi fraction 60 min after treatment was only 40%. These data suggest that hepatic metabolism of DCE is able to promote peroxidative attacks which lead to the degradation of Dol molecules. The pre-treatment of rats with vit. E results in a good, although not complete, prevention of total-Dol depletion after DCE poisoning.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Ascorbic Acid / pharmacology
  • Body Weight / drug effects
  • Chromatography, High Pressure Liquid
  • Dolichols / metabolism*
  • Ethylene Dichlorides / poisoning*
  • Golgi Apparatus / drug effects
  • Golgi Apparatus / metabolism
  • Iron / pharmacology
  • Lipid Peroxidation / drug effects
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Oxidants / poisoning
  • Rats
  • Rats, Wistar
  • Subcellular Fractions / drug effects
  • Subcellular Fractions / metabolism
  • Vitamin E / pharmacology*

Substances

  • Dolichols
  • Ethylene Dichlorides
  • Oxidants
  • Vitamin E
  • ethylene dichloride
  • Iron
  • Ascorbic Acid