Skip directly to search Skip directly to A to Z list Skip directly to page options Skip directly to site content

NIOSHTIC-2 Publications Search

Search Results

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

Authors
Johnson-E; Shvedova-A; Kisin-E; O'Callaghan-J; Kommineni-C; Miller-D
Source
Brain Res 2002 Apr; 933(2):150-163
NIOSHTIC No.
20022299
Abstract
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 h4, 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.
Keywords
Neurotoxicity; Nervous-system; Nervous-system-disorders; Toxins; Antioxidation
Contact
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
CODEN
BRREAP
CAS No.
1406-18-4; 42542-10-9; 51-61-6
Publication Date
20020419
Document Type
Journal Article
Email Address
edj2@cdc.gov
Fiscal Year
2002
NTIS Accession No.
NTIS Price
Issue of Publication
2
ISSN
0006-8993
NIOSH Division
HELD
Source Name
Brain Research
State
WV
TOP