Increased striatal lipid peroxidation after intracerebroventricular MPP+ administration to mice.
Mice received different doses intracerebroventricularly of MPP+ (1-methyl-4-phenylpyridinium ion), the active metabolite of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), a drug which induces a Parkinson model in rodents. Two indexes of lipid peroxidation were monitored at different times after administration: 1) production of thiobarbituric acid-reactive substances and 2) formation of lipid fluorescence products. A regional-selective overproduction of thiobarbituric acid-reactive substances was observed in corpus striatum and midbrain, but not in frontal cortex, cerebellum nor hippocampus. Enhancement was 70% and 198% at 30 and 60 min. in striatum and 88% at 30 min. in midbrain, when compared with respective controls injected intracerebroventricularly with saline solution. MPP+ also induced lipid fluorescence products formation enhancement in corpus striatum. This increase was dose-dependent in the range of MPP+ doses which induced striatal dopamine depletion. Striatal LFP formation was found increased 24 hr after MPP+ administration (38% vs control), indicating long-lasting lipid peroxidation overproduction. These results suggest that lipid peroxidation might be involved in the neurotoxic effects of MPP+ in vivo.
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Department of Neurochemistry, National Institute of Neurology and Neurosurgery, Dr. Manuel Velasco Suàrez, Health Ministry, Mexico 22, D.F.
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D015655:1-Methyl-4-phenylpyridinium / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D007276:Injections, Intraventricular; D050356:Lipid Metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D017392:Thiobarbituric Acid Reactive Substances; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine