Send to

Choose Destination
Brain Res. 2002 Apr 19;933(2):150-63.

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

Author information

Chronic Stress Laboratory, Toxicology and Molecular Biology Branch, National Institute for Occupational Safety and Health/Centers for Disease Control, Mailstop 3014, 1095 Willowdale Road, 26505, Morgantown, WV, USA.


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.

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center