Local striatal infusion of MPP+ does not result in increased hydroxylation after systemic administration of 4-hydroxybenzoate.
Identifieur interne : 003B77 ( Main/Merge ); précédent : 003B76; suivant : 003B78Local striatal infusion of MPP+ does not result in increased hydroxylation after systemic administration of 4-hydroxybenzoate.
Auteurs : L. Ste-Marie [Canada] ; L. Vachon ; C. Bémeur ; J. Lambert ; J. MontgomerySource :
- Free radical biology & medicine [ 0891-5849 ] ; 1999.
English descriptors
- KwdEn :
- 1-Methyl-4-phenylpyridinium (administration & dosage), 1-Methyl-4-phenylpyridinium (toxicity), Allyl Compounds (pharmacology), Animals, Antioxidants (pharmacology), Butylamines (pharmacology), Corpus Striatum (drug effects), Corpus Striatum (metabolism), Dopamine (metabolism), Free Radical Scavengers (administration & dosage), Free Radical Scavengers (metabolism), Hydroxybenzoates (metabolism), Hydroxyl Radical (metabolism), Hydroxylation, Injections, Intraperitoneal, Male, Microdialysis, Monoamine Oxidase Inhibitors (pharmacology), Neurotoxins (administration & dosage), Neurotoxins (toxicity), Parabens (administration & dosage), Parabens (metabolism), Parkinson Disease (etiology), Parkinson Disease (metabolism), Rats, Rats, Sprague-Dawley, Selegiline (pharmacology).
- MESH :
- chemical , administration & dosage : 1-Methyl-4-phenylpyridinium, Free Radical Scavengers, Neurotoxins, Parabens.
- chemical , metabolism : Dopamine, Free Radical Scavengers, Hydroxybenzoates, Hydroxyl Radical, Parabens.
- chemical , pharmacology : Allyl Compounds, Antioxidants, Butylamines, Monoamine Oxidase Inhibitors, Selegiline.
- chemical , toxicity : 1-Methyl-4-phenylpyridinium, Neurotoxins.
- drug effects : Corpus Striatum.
- etiology : Parkinson Disease.
- metabolism : Corpus Striatum, Parkinson Disease.
- Animals, Hydroxylation, Injections, Intraperitoneal, Male, Microdialysis, Rats, Rats, Sprague-Dawley.
Abstract
In vivo bilateral microdialysis in the rat striatum was used to investigate hydroxyl radical formation under basal conditions and after intrastriatal administration of the neurotoxin, 1-methyl-4-phenylpyridinium (MPP+). After a short equilibration period, 4-hydroxybenzoate (4HBZ), which scavenges hydroxyl radicals to produce 3,4-dihydroxybenzoate (34DHB), was injected intraperitoneally 15 min before infusion of MPP+. To evaluate the enzymatic contribution to hydroxyl radical formation, two other series of microdialyses were performed following administration of monoamine oxidase B inhibitors, either 1-deprenyl (selegiline) or MDL 72,974A [(E)-2-(4-fluorophenethyl)-3-fluoroallylamine hydrochloride]. Microdialysate samples were analyzed by high-performance liquid chromatography for catecholamines, 3,4-dihydroxyphenylacetate (DOPAC), homovanillate (HVA), along with the hydroxyl radical adduct, 34DHB and its precursor, 4HBZ. MPP+ administration resulted in a massive release of dopamine along with a decrease in DOPAC and HVA in all three groups. A striking effect in all three groups was noted in which MPP+ resulted in a decrease in interstitial 4HBZ to < 50% of the non-MPP+ -treated side. In absolute terms, the amount of 34DHB produced was low but similar in all three groups, even after unilateral MPP+ infusion. When 34DHB was normalized to 4HBZ release to account for differences in precursor availability, there were no significant differences in the 34DHB/4HBZ ratios either with or without MAO inhibitor treatment or after local MPP+ infusion. Systemic 4HBZ administration appears to result predominantly in intra-cellular sampling of hydroxyl radicals which produces different results from local infusion of trapping agents such as salicylate.
PubMed: 10569632
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pubmed:10569632Le document en format XML
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<term>Allyl Compounds (pharmacology)</term>
<term>Animals</term>
<term>Antioxidants (pharmacology)</term>
<term>Butylamines (pharmacology)</term>
<term>Corpus Striatum (drug effects)</term>
<term>Corpus Striatum (metabolism)</term>
<term>Dopamine (metabolism)</term>
<term>Free Radical Scavengers (administration & dosage)</term>
<term>Free Radical Scavengers (metabolism)</term>
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<term>Microdialysis</term>
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<term>Neurotoxins (toxicity)</term>
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<term>Parabens (metabolism)</term>
<term>Parkinson Disease (etiology)</term>
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<term>Rats</term>
<term>Rats, Sprague-Dawley</term>
<term>Selegiline (pharmacology)</term>
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<term>Hydroxylation</term>
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<front><div type="abstract" xml:lang="en">In vivo bilateral microdialysis in the rat striatum was used to investigate hydroxyl radical formation under basal conditions and after intrastriatal administration of the neurotoxin, 1-methyl-4-phenylpyridinium (MPP+). After a short equilibration period, 4-hydroxybenzoate (4HBZ), which scavenges hydroxyl radicals to produce 3,4-dihydroxybenzoate (34DHB), was injected intraperitoneally 15 min before infusion of MPP+. To evaluate the enzymatic contribution to hydroxyl radical formation, two other series of microdialyses were performed following administration of monoamine oxidase B inhibitors, either 1-deprenyl (selegiline) or MDL 72,974A [(E)-2-(4-fluorophenethyl)-3-fluoroallylamine hydrochloride]. Microdialysate samples were analyzed by high-performance liquid chromatography for catecholamines, 3,4-dihydroxyphenylacetate (DOPAC), homovanillate (HVA), along with the hydroxyl radical adduct, 34DHB and its precursor, 4HBZ. MPP+ administration resulted in a massive release of dopamine along with a decrease in DOPAC and HVA in all three groups. A striking effect in all three groups was noted in which MPP+ resulted in a decrease in interstitial 4HBZ to < 50% of the non-MPP+ -treated side. In absolute terms, the amount of 34DHB produced was low but similar in all three groups, even after unilateral MPP+ infusion. When 34DHB was normalized to 4HBZ release to account for differences in precursor availability, there were no significant differences in the 34DHB/4HBZ ratios either with or without MAO inhibitor treatment or after local MPP+ infusion. Systemic 4HBZ administration appears to result predominantly in intra-cellular sampling of hydroxyl radicals which produces different results from local infusion of trapping agents such as salicylate.</div>
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