Brain antioxidant systems in human methamphetamine users.
Animal data suggest that the widely abused psychostimulant methamphetamine can damage brain dopamine neurones by causing dopamine-dependent oxidative stress; however, the relevance to human methamphetamine users is unclear. We measured levels of key antioxidant defences [reduced (GSH) and oxidized (GSSG) glutathione, six major GSH system enzymes, copper-zinc superoxide dismutase (CuZnSOD), uric acid] that are often altered after exposure to oxidative stress, in autopsied brain of human methamphetamine users and matched controls. Changes in the total (n = 20) methamphetamine group were limited to the dopamine-rich caudate (the striatal subdivision with the most severe dopamine loss) in which only activity of CuZnSOD (+ 14%) and GSSG levels (+ 58%) were changed. In the six methamphetamine users with severe (- 72 to - 97%) caudate dopamine loss, caudate CuZnSOD activity (+ 20%) and uric acid levels (+ 63%) were increased with a trend for decreased (- 35%) GSH concentration. Our data suggest that brain levels of many antioxidant systems are preserved in methamphetamine users and that GSH depletion, commonly observed during severe oxidative stress, might occur only with severe dopamine loss. Increased CuZnSOD and uric acid might reflect compensatory responses to oxidative stress. Future studies are necessary to establish whether these changes are associated with oxidative brain damage in human methamphetamine users.
Mirecki
Anna
A
Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, Canada M5T 1R8.
Fitzmaurice
Paul
P
Ang
Lee
L
Kalasinsky
Kathryn S
KS
Peretti
Frank J
FJ
Aiken
Sally S
SS
Wickham
Dennis J
DJ
Sherwin
Allan
A
Nobrega
José N
JN
Forman
Henry J
HJ
Kish
Stephen J
SJ
D000293:Adolescent; D000328:Adult; D019969:Amphetamine-Related Disorders / Q000378:metabolism*; D000975:Antioxidants / Q000032:analysis / Q000378:metabolism*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D001923:Brain Chemistry; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D004798:Enzymes / Q000032:analysis / Q000378:metabolism; D005260:Female; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D006801:Humans; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D011180:Postmortem Changes; D012044:Regression Analysis; D013482:Superoxide Dismutase / Q000378:metabolism; D014527:Uric Acid / Q000378:metabolism
D000975:Antioxidants; D000697:Central Nervous System Stimulants; D004798:Enzymes; D014527:Uric Acid; D008694:Methamphetamine; D013482:Superoxide Dismutase; D005978:Glutathione; D019803:Glutathione Disulfide; D004298:Dopamine