Systemic administration of antioxidants does not protect mice against the dopaminergic neurotoxicity of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP).
We examined whether DA neurotoxicity of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) can be prevented by combined systemic administration of antioxidants. C57 black mice were injected s.c. with MPTP (30 mg/kg), once daily for two days, alone, or with ascorbic acid (1 g/kg), alpha-tocopherol (100 mg/kg), or dimethylsulfoxide (50 microliters) i.p. for two days before, two days with and two days after MPTP, and decapitated 30 days later. MPTP once (30 mg/kg), alone, or with ascorbic acid (200 mg/kg) or cysteamine (75 mg/kg), two days before, one day with and 4 days after, and decapitated 10 days post-MPTP. MPTP once (15 mg/kg), alone, or with ascorbic acid (500 mg/kg, alpha-tocopherol (100 mg/kg), cysteamine (50 mg/kg) or sodium selenite (2.5 mg/kg), 90 min before and again 90 min after MPTP, and decapitated 7 days later. In all experiments, the marked striatal DA depletions produced by MPTP alone (by 40-70% from controls) were unchanged by cotreatments with the various antioxidants. Findings do not favor intraneuronal generation of superoxides and related cytotoxic free radicals as a major factor in the DA neurotoxicity of MPTP. They suggest that if natural Parkinson's disease is caused by an MPTP-like neurotoxin, early treatment with antioxidants is unlikely to protect nigrostriatal neurons and prevent disease progression.
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage*; D001205:Ascorbic Acid / Q000008:administration & dosage; D001923:Brain Chemistry / Q000187:drug effects*; D003342:Corpus Striatum / Q000187:drug effects; D004121:Dimethyl Sulfoxide / Q000008:administration & dosage; D004298:Dopamine / Q000378:metabolism*; D004334:Drug Administration Schedule; D004338:Drug Combinations; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009498:Neurotoxins; D011725:Pyridines / Q000008:administration & dosage* / Q000378:metabolism; D013378:Substantia Nigra / Q000187:drug effects; D014810:Vitamin E / Q000008:administration & dosage
D000975:Antioxidants; D004338:Drug Combinations; D009498:Neurotoxins; D011725:Pyridines; D014810:Vitamin E; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D001205:Ascorbic Acid; D004298:Dopamine; D004121:Dimethyl Sulfoxide