4-Hydroxytamoxifen attenuates methamphetamine-induced nigrostriatal dopaminergic toxicity in intact and gonadetomized mice.
The present study was undertaken to assess the ability of 4-hydroxytamoxifen (4-OHT) to alter methamphetamine-induced nigrostriatal dopaminergic toxicity. Three daily doses of 4-OHT (6 micro g/day) effectively attenuated methamphetamine-induced nigrostriatal dopamine depletions in both sexes of intact and gonadectomized C57BL/6 J mice. 4-OHT alone did not alter the dopamine content levels in the striatum. Both male and female mice exhibited similar Cu, Zn-superoxide dismutase protein levels in the striata whether after gonadectomy or 4-OHT treatment. Furthermore, basal body temperature and methamphetamine-induced hyperthermia were not affected by 4-OHT treatment in either sex of mice. Using a lucigenen-derived chemiluminescence assay, we found that 4-OHT by itself can serve as a potent superoxide anion radical scavenger in vitro. The protective effects of 4-OHT against methamphetamine-induced nigrostriatal dopamine depletion can be, in part, due to its antioxidative characteristics. The free radical-scavenging ability of 4-OHT calls for further investigations for its uses in clinical practice.
Kuo
Yu-Min
YM
Department of Cell Biology and Anatomy, National Cheng Kung University College of Medicine, Tainan, Taiwan.
Chen
Hsiang-Hua
HH
Shieh
Chih-Chang
CC
Chuang
Kuo-Pin
KP
Cherng
Chianfang G
CG
Yu
Lung
L
D015102:3,4-Dihydroxyphenylacetic Acid / Q000032:analysis; D000818:Animals; D015153:Blotting, Western; D001831:Body Temperature / Q000187:drug effects; D002369:Castration / Q000379:methods; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D008297:Male; D008694:Methamphetamine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D017072:Neostriatum / Q000187:drug effects* / Q000378:metabolism; D009498:Neurotoxins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D012737:Sex Factors; D013482:Superoxide Dismutase / Q000378:metabolism / Q000494:pharmacology; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000494:pharmacology*; D013997:Time Factors; D014969:Xanthine Oxidase / Q000378:metabolism
D004965:Estrogen Antagonists; D009498:Neurotoxins; D013629:Tamoxifen; D015102:3,4-Dihydroxyphenylacetic Acid; C016601:afimoxifene; D008694:Methamphetamine; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase; D004298:Dopamine