Protective effects of Vitamin E on endocrine disruptors, PCB-induced dopaminergic neurotoxicity

Toxicology. 2005 Dec 15;216(2-3):140-6. doi: 10.1016/j.tox.2005.08.017. Epub 2005 Sep 21.

Abstract

The protective effect of an antioxidant, Vitamin E (dl-alpha-tocopherol, 100 mg/kg/day, 8 days p.o. in vivo and 10 and 50 microM in vitro) was tested against PCB-induced neurotoxicity.

In vivo studies: Microdialysis was used to investigate changes in the striatal extracellular dopamine level and in p-nNOS expression in PCB-treated (Aroclor 1254, 10 microg/ml, 2 microl/min, 5 h; 6 microg was infused by microdialysis probe) rats.

In vitro studies: Cell viability and levels of p-nNOS expression were observed in PCB-treated (Aroclor 1254, 5 microg/ml) immortalized dopaminergic cell line (CATH.a cells).

Results: Treatment with PCB: (1) decreased the extracellular dopamine level in rat striatum, (2) increased p-nNOS expression both in rat striatal tissue and in CATH.a cells, (3) reduced the cell viability of, and (4) increased LDH release by CATH.a cells. However, Vitamin E showed a protective effect against PCB-induced toxicity and downregulation of the extracellular dopamine level. These results indicate that Vitamin E may have neuroprotective effects by inhibiting PCB-induced nNOS phosphorylation.

MeSH terms

  • Administration, Oral
  • Animals
  • Cell Culture Techniques
  • Cell Survival / drug effects
  • Chromatography, High Pressure Liquid
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism
  • Dopamine / metabolism*
  • Endocrine Disruptors*
  • Immunoblotting
  • Male
  • Microdialysis
  • Neurotoxicity Syndromes / etiology
  • Neurotoxicity Syndromes / metabolism
  • Neurotoxicity Syndromes / prevention & control*
  • Nitric Oxide Synthase Type I / drug effects
  • Nitric Oxide Synthase Type I / metabolism*
  • Phosphorylation / drug effects
  • Polychlorinated Biphenyls / antagonists & inhibitors
  • Polychlorinated Biphenyls / toxicity*
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors
  • Up-Regulation / drug effects
  • Vitamin E / administration & dosage
  • Vitamin E / pharmacology*
  • Vitamin E / therapeutic use

Substances

  • Endocrine Disruptors
  • Vitamin E
  • Polychlorinated Biphenyls
  • Nitric Oxide Synthase Type I
  • Dopamine