Systemic administration of antioxidants does not protect mice against the dopaminergic neurotoxicity of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP)

Giora Martinovits, Eldad Melamed, Oren Cohen, Jutta Rosenthal, Anat Uzzan

Research output: Contribution to journalArticlepeer-review

Abstract

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 (1) MPTP (30 mg/kg), once daily for two days, alone, or with ascorbic acid (1 g/kg), α-tocopherol (100 mg/kg), or dimethylsufoxide (50 μl) i.p. for two days before, two days with and two days after MPTP, and decapitated 30 days later. (2) 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. (3) MPTP once (15 mg/kg), alone, or with ascorbic acid (500 mg/kg), α-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.

Original languageEnglish
Pages (from-to)192-197
Number of pages6
JournalNeuroscience Letters
Volume69
Issue number2
DOIs
StatePublished - 29 Aug 1986
Externally publishedYes

Keywords

  • 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine
  • MPTP
  • Parkinson's disease
  • dopamine
  • mouse
  • neurotoxin
  • nigrostriatal neuron

Fingerprint

Dive into the research topics of 'Systemic administration of antioxidants does not protect mice against the dopaminergic neurotoxicity of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP)'. Together they form a unique fingerprint.

Cite this