title: Effect of MPTP on brain mitochondrial H2O2 and ATP production and on dopamine and DOPAC in the striatum.
abstract: An experimental rat model of Parkinson's disease was established by injecting rats directly in the striatum with the neurotoxic agent 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In order to study the action mechanism of this neurotoxic agent, MPTP and its main metabolite 1-methyl-4-phenylpyridinium (MPP+) were also added to suspensions of pyruvate/malate-supplemented nonsynaptic brain mitochondria, and the rates of hydrogen peroxide and ATP production were measured. Intrastriatal administration of MPTP produced a pronounced decrease in striatal dopamine levels (p < 0.005) and a strong increase in 3,4-hydroxiphenylacetic acid/dopamine ratio (an indicator of dopamine catabolism; p < 0.005) in relation to controls, as evaluated by in situ microdialysis. MPTP addition to rat brain mitochondria increased hydrogen peroxide production by 90%, from 1.37+/-0.35 to 2.59+/-0.48 nanomoles of H2O2/minute . mg of protein (p < 0.01). The metabolite MPP+ produced a marked decrease on the rate of ATP production of brain mitochondria (p < 0.005). These findings support the mitochondria-oxidative stress-energy failure hypothesis of MPTP-induced brain neurotoxicity.
authors.affiliation: Department of Animal Biology-II (Animal Physiology), Faculty of Biology, Complutense University of Madrid, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Fabre
authors.forename: J
authors.initials: J
authors.lastname: Monserrat
authors.forename: A
authors.initials: A
authors.lastname: Herrero
authors.forename: G
authors.initials: G
authors.lastname: Barja
authors.forename: M L
authors.initials: ML
authors.lastname: Leret
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000378:metabolism; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000096:biosynthesis*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism*; D020267:MPTP Poisoning / Q000378:metabolism*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
chemical_list: D015102:3,4-Dihydroxyphenylacetic Acid; D000255:Adenosine Triphosphate; D006861:Hydrogen Peroxide; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine