d-MDMA during vitamin E deficiency: effects on dopaminergic neurotoxicity and hepatotoxicity

Brain Res. 2002 Apr 19;933(2):150-63. doi: 10.1016/s0006-8993(02)02313-2.


The mechanism of 3,4-methylenedioxymethamphetamine (d-MDMA)-induced neurotoxicity may involve formation of toxic radical species. Endogenous defenses against toxic radical species include tissue stores of vitamin E, and thiols. We examined whether vitamin E deficiency could alter d-MDMA-induced neurotoxicity by administration of the drug to animals with diet induced vitamin E deficiency. Brain vitamin E levels in deficient mice were reduced 75% compared to sufficient animals. Animals received d-MDMA 5 or 10 mg/kg or saline (delivered every 2 hx4, s.c.). Diet slightly altered d-MDMA-induced temperature modulation. In brain, MDMA treatment reduced vitamin E, total antioxidant reserve and protein thiols 72 h after the first dose. In liver, MDMA treatment reduced glutathione and total antioxidant reserve at the same time point. The vitamin E-deficient group, treated with the low dose of d-MDMA, exhibited neurotoxic responses, including reduced striatal dopamine (47%) and elevated GFAP protein (3-fold): while the sufficient diet group was not altered. The higher d-MDMA dose caused neurotoxic responses in both diet groups. Liver toxicity was determined by histopathologic examination. d-MDMA caused hepatic necrosis that was more severe in vitamin E deficient than sufficient mice. These data indicate that (1) d-MDMA administration reduces antioxidant measures at a time coincident with d-MDMA-induced neuronal damage and (2) vitamin E deficiency increases susceptibility to d-MDMA-induced neurotoxicity and hepatic necrosis.

MeSH terms

  • Adrenergic Uptake Inhibitors / toxicity*
  • Animals
  • Antioxidants / metabolism
  • Body Temperature Regulation / drug effects
  • Body Temperature Regulation / physiology
  • Brain / drug effects*
  • Brain / metabolism
  • Brain / pathology
  • Cell Death / drug effects
  • Cell Death / physiology
  • Dopamine / metabolism*
  • Dose-Response Relationship, Drug
  • Down-Regulation / drug effects
  • Down-Regulation / physiology
  • Food, Formulated
  • Free Radical Scavengers / metabolism
  • Free Radicals / metabolism
  • Hepatocytes / drug effects
  • Hepatocytes / metabolism
  • Hepatocytes / pathology
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • N-Methyl-3,4-methylenedioxyamphetamine / toxicity*
  • Necrosis
  • Neurons / drug effects*
  • Neurons / metabolism
  • Neurons / pathology
  • Neurotoxins / toxicity*
  • Vitamin E / metabolism
  • Vitamin E Deficiency / metabolism*
  • Vitamin E Deficiency / pathology
  • Vitamin E Deficiency / physiopathology


  • Adrenergic Uptake Inhibitors
  • Antioxidants
  • Free Radical Scavengers
  • Free Radicals
  • Neurotoxins
  • Vitamin E
  • N-Methyl-3,4-methylenedioxyamphetamine
  • Dopamine