D-MDMA During Vitamin E Deficiency: Effects on Dopaminergic Neurotoxicity and Hepatotoxicity

Details

• Personal Author:
  Johnson E ; Kisin E ; Kommineni C ; Miller D ; O'Callaghan J ; Shvedova A
• Description:
  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 h×4, 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. [Description provided by NIOSH]
• Subjects:
  Hazardous Substances Nervous System Nervous System Diseases Occupational Health Safety
• Keywords:
  Alpha-tocopherol Deficiency Antioxidation Author Keywords: Dopamine D-MDMA Nervous-system Nervous-system-disorders Neurotoxicity Serotonin Striatum Toxins
• ISSN:
  0006-8993
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  150-163
• Volume:
  933
• Issue:
  2
• NIOSHTIC Number:
  nn:20022299
• Citation:
  Brain Res 2002 Apr; 933(2):150-163
• Contact Point Address:
  Chronic Stress Laboratory, Toxicology and Molecular Biology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health/Centers for Disease Control, Mailstop 3014, 1095 Willowdale Road, Morgantown, WV 26505, USA
• Email:
  edj2@cdc.gov
• CAS Registry Number:
  3,4-Methylenedioxymethamphetamine (CAS RN 42542-10-9) ; Dopamine (CAS RN 51-61-6) ; Vitamin E (CAS RN 1406-18-4)
• Federal Fiscal Year:
  2002
• Peer Reviewed:
  True
• Source Full Name:
  Brain Research
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:cb89cbf78ea200776400d80becd35a503686c214b19cebf2417e62d26b07676ac096f6088608a652c65d249e46283346c1d6fadbc76b05978a34a01492e5cce0
• Download URL:
  https://stacks.cdc.gov/view/cdc/199117/cdc_199117_DS1.pdf
• File Type:
  [PDF - 2.22 MB ]