title: Levels of 4-hydroxynonenal and malondialdehyde are increased in brain of human chronic users of methamphetamine.
abstract: Animal studies suggest that the widely used psychostimulant drug methamphetamine (MA) can harm brain dopamine neurones, possibly by causing oxidative damage. However, evidence of oxidative damage in brain of human MA users is lacking. We tested the hypothesis that levels of two "gold standard" products generated from lipid peroxidation, 4-hydroxynonenal (one of the most reactive lipid peroxidation aldehyde products) and malondialdehyde, would be elevated in post mortem brain of 16 dopamine-deficient chronic MA users compared with those in 21 matched control subjects. Derivatized aldehyde concentrations were determined by gas chromatography-mass spectrometry. In the MA group, we found significantly increased levels of 4-hydroxynonenal and malondialdehyde in the dopamine-rich caudate nucleus (by 67 and 75%, respectively) and to a lesser extent in frontal cortex (48 and 36%, respectively) but not in the cerebellar cortex. Approximately half of the MA users had levels of 4-hydroxynonenal falling above the upper limit of the control range in caudate and frontal cortex. A subgroup of MA users with high brain drug levels had higher concentrations of the aldehydes. Our data suggest that MA exposure in human causes, as in experimental animals, above-normal formation of potentially toxic lipid peroxidation products in brain. This provides evidence for involvement of oxygen-based free radicals in the action of MA in both dopamine-rich (caudate) and -poor (cerebral cortex) areas of human brain.
authors.affiliation: Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario M5T 1R8, Canada.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Fitzmaurice
authors.forename: Junchao
authors.initials: J
authors.lastname: Tong
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Yazdanpanah
authors.forename: Peter P
authors.initials: PP
authors.lastname: Liu
authors.forename: Kathryn S
authors.initials: KS
authors.lastname: Kalasinsky
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Kish
mesh_terms: D000328:Adult; D000367:Age Factors; D000447:Aldehydes / Q000032:analysis*; D019969:Amphetamine-Related Disorders / Q000378:metabolism*; D001921:Brain / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D004298:Dopamine / Q000032:analysis; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008297:Male; D008315:Malondialdehyde / Q000032:analysis*; D008694:Methamphetamine / Q000633:toxicity*; D014527:Uric Acid / Q000032:analysis
chemical_list: D000447:Aldehydes; D014527:Uric Acid; D008694:Methamphetamine; D008315:Malondialdehyde; C027576:4-hydroxy-2-nonenal; D004298:Dopamine