Local striatal infusion of MPP+ does not result in increased hydroxylation after systemic administration of 4-hydroxybenzoate

Free Radic Biol Med. 1999 Nov;27(9-10):997-1007. doi: 10.1016/s0891-5849(99)00170-7.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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


  • Allyl Compounds
  • Antioxidants
  • Butylamines
  • Free Radical Scavengers
  • Hydroxybenzoates
  • Monoamine Oxidase Inhibitors
  • Neurotoxins
  • Parabens
  • mofegiline
  • Selegiline
  • Hydroxyl Radical
  • protocatechuic acid
  • 4-hydroxybenzoic acid
  • 1-Methyl-4-phenylpyridinium
  • Dopamine