Local striatal infusion of MPP+ does not result in increased hydroxylation after systemic administration of 4-hydroxybenzoate.
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.
Ste-Marie
L
L
Centre de recherche, Hôpital Notre-Dame, Centre hospitalier de l'Université de Montréal, Département de nutrition, Canada.
Vachon
L
L
Bémeur
C
C
Lambert
J
J
Montgomery
J
J
D015655:1-Methyl-4-phenylpyridinium / Q000008:administration & dosage / Q000633:toxicity*; D000498:Allyl Compounds / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002082:Butylamines / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D016166:Free Radical Scavengers / Q000008:administration & dosage / Q000378:metabolism; D062385:Hydroxybenzoates / Q000378:metabolism; D017665:Hydroxyl Radical / Q000378:metabolism; D006900:Hydroxylation; D007274:Injections, Intraperitoneal; D008297:Male; D017551:Microdialysis; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D009498:Neurotoxins / Q000008:administration & dosage / Q000633:toxicity*; D010226:Parabens / Q000008:administration & dosage / Q000378:metabolism*; D010300:Parkinson Disease / Q000209:etiology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012642:Selegiline / Q000494:pharmacology
D000498:Allyl Compounds; D000975:Antioxidants; D002082:Butylamines; D016166:Free Radical Scavengers; D062385:Hydroxybenzoates; D008996:Monoamine Oxidase Inhibitors; D009498:Neurotoxins; D010226:Parabens; C058000:mofegiline; D012642:Selegiline; D017665:Hydroxyl Radical; C009091:protocatechuic acid; C038193:4-hydroxybenzoic acid; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine