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

Johnson E; Shvedova A; Kisin E; O'Callaghan J; Kommineni C; Miller D

Brain Res 2002 Apr; 933(2):150-163

https://doi.org/10.1016/S0006-8993(02)02313-2

20022299

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.

Neurotoxicity; Nervous-system; Nervous-system-disorders; Toxins; Antioxidation; Author Keywords: Dopamine; Striatum; Serotonin; d-MDMA; Alpha-tocopherol deficiency

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

BRREAP

1406-18-4; 42542-10-9; 51-61-6

20020419

Journal Article

edj2@cdc.gov

2002

2

0006-8993

HELD

Brain Research

WV