Sulfhydryl drugs reduce neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the mouse.
Striatal levels of dopamine and its metabolites 3-methoxy-4-hydroxy-phenylacetic acid (DOPAC) and homovanillic acid (HVA) decreased 7 days after subcutaneous injection of MPTP (20 mg/kg) to the mouse. Striatal GSH contents decreased and GSSG/GSH ratios increased one hour after subcutaneous administration of MPTP. Pretreatments of both cysteamine (200 mg/kg, s.c.) and dimercaprol (20 mg/kg, i.m.) reduced the MPTP-induced decreases in striatal dopamine, DOPAC and HVA, and also prevented the MPTP-induced decreases in GSH levels and increases in GSSG/GSH ratios. On the other hand, injection of cysteamine did not modify the MPTP-induced decreases in striatal levels of dopamine and its metabolites when it was done 2 hours after MPTP administration. Moreover, pretreatment of cysteamine did not affect striatal concentrations of MPP+ in MPTP-treated mice. These results suggest that sulfhydryl drugs such as cysteamine and dimercaprol may reduce neurotoxicity of MPTP probably via changes in redox cycle of glutathione in the brain.
Oishi
T
T
Department of Neurology, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan.
Hasegawa
E
E
Murai
Y
Y
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D003543:Cysteamine / Q000494:pharmacology; D004112:Dimercaprol / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents / Q000037:antagonists & inhibitors* / Q000633:toxicity; D005978:Glutathione / Q000378:metabolism; D006719:Homovanillic Acid / Q000378:metabolism; D020267:MPTP Poisoning; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009410:Nerve Degeneration / Q000187:drug effects; D009422:Nervous System Diseases / Q000517:prevention & control*; D011726:Pyridinium Compounds / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000494:pharmacology*
D015259:Dopamine Agents; D011726:Pyridinium Compounds; D013438:Sulfhydryl Compounds; D004112:Dimercaprol; D015102:3,4-Dihydroxyphenylacetic Acid; C048977:1-methyl-4-(2'-methylphenyl)-1,2,3,6-tetrahydropyridine; C026560:1-(4-methoxyphenyl)pyridinium; D003543:Cysteamine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D005978:Glutathione; D004298:Dopamine; D006719:Homovanillic Acid