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OVEREXPRESSION OF HUMAN COPPER/ZINC SUPEROXIDE DISMUTASE IN TRANSGENIC MICE ATTENUATES OXIDATIVE
 

Summary: OVEREXPRESSION OF HUMAN COPPER/ZINC SUPEROXIDE
DISMUTASE IN TRANSGENIC MICE ATTENUATES OXIDATIVE
STRESS CAUSED BY METHYLENEDIOXYMETHAMPHETAMINE
(ECSTASY)
S. JAYANTHI,* B. LADENHEIM,* A. M. ANDREWS and J. L. CADET*
*Molecular Neuropsychiatry Section, Laboratory of Clinical Science, NIH/NIDA,
Bethesda, MD 20892, U.S.A.
Abstract--Administration of 3,4-methylenedioxymethamphetamine (4 × 20 mg/kg) to non-transgenic
CD-1 mice caused marked depletion in dopamine, 3,4-dihydroxyphenylacetic acid and 5-hydroxytrypta-
mine in the caudate­putamen. There were no significant changes in serotonergic markers in the hippo-
campus and frontal cortex. Homozygous and heterozygous copper/zinc superoxide dismutase transgenic
mice show partial protection against the toxic effects of 3,4-methylenedioxymethamphetamine on striatal
dopaminergic markers. In addition, 3,4-methylenedioxymethamphetamine injections caused marked
decreases in copper/zinc superoxide dismutase activity in the frontal cortex, caudate­putamen and hippo-
campus of wild-type mice. Moreover, there were concomitant 3,4-methylenedioxymethamphetamine-
induced decreases in catalase activity in the caudate­putamen and hippocampus, decreases in glutathione
peroxidase activity in the frontal cortex as well as increases in lipid peroxidation in the frontal cortex,
caudate­putamen, and hippocampus of wild-type mice. In contrast, administration of 3,4-methylenedioxy-
methamphetamine to homozygous superoxide dismutase transgenic mice caused no significant changes in
antioxidant enzyme activities nor in lipid peroxidation.

  

Source: Andrews, Anne M. - Huck Institutes of the Life Sciences, Pennsylvania State University

 

Collections: Biology and Medicine