Local striatal infusion of MPP+ does not result in increased hydroxylation after systemic administration of 4-hydroxybenzoate.
Identifieur interne : 000062 ( Ncbi/Checkpoint ); précédent : 000061; suivant : 000063Local 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
Affiliations:
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Bémeur</name></author><author><name sortKey="Lambert, J" sort="Lambert, J" uniqKey="Lambert J" first="J" last="Lambert">J. Lambert</name></author><author><name sortKey="Montgomery, J" sort="Montgomery, J" uniqKey="Montgomery J" first="J" last="Montgomery">J. Montgomery</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="1999">1999</date><idno type="RBID">pubmed:10569632</idno><idno type="pmid">10569632</idno><idno type="wicri:Area/PubMed/Corpus">001677</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001677</idno><idno type="wicri:Area/PubMed/Curation">001677</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">001677</idno><idno type="wicri:Area/PubMed/Checkpoint">001677</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">001677</idno><idno type="wicri:Area/Ncbi/Merge">000062</idno><idno type="wicri:Area/Ncbi/Curation">000062</idno><idno type="wicri:Area/Ncbi/Checkpoint">000062</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Local striatal infusion of MPP+ does not result in increased hydroxylation after systemic administration of 4-hydroxybenzoate.</title><author><name sortKey="Ste Marie, L" sort="Ste Marie, L" uniqKey="Ste Marie L" first="L" last="Ste-Marie">L. Ste-Marie</name><affiliation wicri:level="1"><nlm:affiliation>Centre de recherche, Hôpital Notre-Dame, Centre hospitalier de l'Université de Montréal, Département de nutrition, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Centre de recherche, Hôpital Notre-Dame, Centre hospitalier de l'Université de Montréal, Département de nutrition</wicri:regionArea><wicri:noRegion>Département de nutrition</wicri:noRegion></affiliation></author><author><name sortKey="Vachon, L" sort="Vachon, L" uniqKey="Vachon L" first="L" last="Vachon">L. Vachon</name></author><author><name sortKey="Bemeur, C" sort="Bemeur, C" uniqKey="Bemeur C" first="C" last="Bémeur">C. Bémeur</name></author><author><name sortKey="Lambert, J" sort="Lambert, J" uniqKey="Lambert J" first="J" last="Lambert">J. Lambert</name></author><author><name sortKey="Montgomery, J" sort="Montgomery, J" uniqKey="Montgomery J" first="J" last="Montgomery">J. Montgomery</name></author></analytic><series><title level="j">Free radical biology & medicine</title><idno type="ISSN">0891-5849</idno><imprint><date when="1999" type="published">1999</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>1-Methyl-4-phenylpyridinium (administration & dosage)</term><term>1-Methyl-4-phenylpyridinium (toxicity)</term><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><term>Hydroxybenzoates (metabolism)</term><term>Hydroxyl Radical (metabolism)</term><term>Hydroxylation</term><term>Injections, Intraperitoneal</term><term>Male</term><term>Microdialysis</term><term>Monoamine Oxidase Inhibitors (pharmacology)</term><term>Neurotoxins (administration & dosage)</term><term>Neurotoxins (toxicity)</term><term>Parabens (administration & dosage)</term><term>Parabens (metabolism)</term><term>Parkinson Disease (etiology)</term><term>Parkinson Disease (metabolism)</term><term>Rats</term><term>Rats, Sprague-Dawley</term><term>Selegiline (pharmacology)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>1-Methyl-4-phenylpyridinium</term><term>Free Radical Scavengers</term><term>Neurotoxins</term><term>Parabens</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Dopamine</term><term>Free Radical Scavengers</term><term>Hydroxybenzoates</term><term>Hydroxyl Radical</term><term>Parabens</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Allyl Compounds</term><term>Antioxidants</term><term>Butylamines</term><term>Monoamine Oxidase Inhibitors</term><term>Selegiline</term></keywords><keywords scheme="MESH" type="chemical" qualifier="toxicity" xml:lang="en"><term>1-Methyl-4-phenylpyridinium</term><term>Neurotoxins</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Corpus Striatum</term></keywords><keywords scheme="MESH" qualifier="etiology" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Corpus Striatum</term><term>Parkinson Disease</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Hydroxylation</term><term>Injections, Intraperitoneal</term><term>Male</term><term>Microdialysis</term><term>Rats</term><term>Rats, Sprague-Dawley</term></keywords></textClass></profileDesc></teiHeader><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></front></TEI><affiliations><list><country><li>Canada</li></country></list><tree><noCountry><name sortKey="Bemeur, C" sort="Bemeur, C" uniqKey="Bemeur C" first="C" last="Bémeur">C. Bémeur</name><name sortKey="Lambert, J" sort="Lambert, J" uniqKey="Lambert J" first="J" last="Lambert">J. Lambert</name><name sortKey="Montgomery, J" sort="Montgomery, J" uniqKey="Montgomery J" first="J" last="Montgomery">J. Montgomery</name><name sortKey="Vachon, L" sort="Vachon, L" uniqKey="Vachon L" first="L" last="Vachon">L. Vachon</name></noCountry><country name="Canada"><noRegion><name sortKey="Ste Marie, L" sort="Ste Marie, L" uniqKey="Ste Marie L" first="L" last="Ste-Marie">L. Ste-Marie</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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