The dopamine agonist pramipexole scavenges hydroxyl free radicals induced by striatal application of 6-hydroxydopamine in rats: an in vivo microdialysis study

B Ferger, Peter Teismann, J Mierau

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Hydroxyl free radical production seems to play an important role in the pathogenesis of Parkinson's disease. In the present study, we investigated the dopamine agonists pramipexole and pergolide as well as the nitrone compound S-PBN (N-tert-butyl-alpha-(2-sulfophenyl)nitrone) to reduce hydroxyl radical formation. Microdialysis experiments were carried out in non-anaesthetized Wistar rats. Salicylate was incorporated into the perfusion fluid to measure indirectly hydroxyl radicals indicated by 2,3-dihydroxybenzoic acid (2,3-DHBA). Local perfusion with 0.2 or 2 nmol/2 microl/min 6-hydroxydopamine (6-OHDA) via the microdialysis probe significantly increased 2,3-DHBA levels 14-fold and 47-fold, respectively. Systemic application of either pergolide (0.05 mg/kg) or pramipexole (1 mg/kg) failed to significantly reduce 6-OHDA-induced hydroxyl radical production. In contrast, a 40 min pretreatment with pramipexole (2 and 10 nmol/2 microl/min via the probe) before onset of 6-OHDA perfusion, significantly attenuated 2, 3-DHBA levels compared with vehicle controls. S-PBN pretreatment (2 nmol/2 microl/min) was not effective to reduce 2,3-DHBA levels. In conclusion, pramipexole was able to reduce hydroxyl radical levels induced by 6-OHDA in vivo after local application. This property of pramipexole may be beneficial under conditions of enhanced hydroxyl radical formation in parkinsonian brains and may add to its well known dopamine D(2)-like receptor agonistic effects.
Original languageEnglish
Pages (from-to)216-223
Number of pages8
JournalBrain Research
Volume883
Issue number2
DOIs
Publication statusPublished - 17 Nov 2000

Fingerprint

Corpus Striatum
Oxidopamine
Dopamine Agonists
Microdialysis
Hydroxyl Radical
Free Radicals
Pergolide
Perfusion
Salicylates
Parkinson Disease
pramipexole
Wistar Rats
Dopamine
Brain
2,3-dihydroxybenzoic acid

Keywords

  • Adrenergic Agents
  • Animals
  • Benzothiazoles
  • Corpus Striatum
  • Dopamine
  • Dopamine Agonists
  • Hydroxybenzoic Acids
  • Hydroxyl Radical
  • Male
  • Microdialysis
  • Oxidopamine
  • Pergolide
  • Rats
  • Rats, Wistar
  • Thiazoles
  • Pramipexole
  • 6-Hydroxydopamine
  • Parkinson’s disease
  • Salicylate assay
  • Radical

Cite this

The dopamine agonist pramipexole scavenges hydroxyl free radicals induced by striatal application of 6-hydroxydopamine in rats : an in vivo microdialysis study. / Ferger, B; Teismann, Peter; Mierau, J.

In: Brain Research, Vol. 883, No. 2, 17.11.2000, p. 216-223.

Research output: Contribution to journalArticle

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T1 - The dopamine agonist pramipexole scavenges hydroxyl free radicals induced by striatal application of 6-hydroxydopamine in rats

T2 - an in vivo microdialysis study

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AU - Teismann, Peter

AU - Mierau, J

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AB - Hydroxyl free radical production seems to play an important role in the pathogenesis of Parkinson's disease. In the present study, we investigated the dopamine agonists pramipexole and pergolide as well as the nitrone compound S-PBN (N-tert-butyl-alpha-(2-sulfophenyl)nitrone) to reduce hydroxyl radical formation. Microdialysis experiments were carried out in non-anaesthetized Wistar rats. Salicylate was incorporated into the perfusion fluid to measure indirectly hydroxyl radicals indicated by 2,3-dihydroxybenzoic acid (2,3-DHBA). Local perfusion with 0.2 or 2 nmol/2 microl/min 6-hydroxydopamine (6-OHDA) via the microdialysis probe significantly increased 2,3-DHBA levels 14-fold and 47-fold, respectively. Systemic application of either pergolide (0.05 mg/kg) or pramipexole (1 mg/kg) failed to significantly reduce 6-OHDA-induced hydroxyl radical production. In contrast, a 40 min pretreatment with pramipexole (2 and 10 nmol/2 microl/min via the probe) before onset of 6-OHDA perfusion, significantly attenuated 2, 3-DHBA levels compared with vehicle controls. S-PBN pretreatment (2 nmol/2 microl/min) was not effective to reduce 2,3-DHBA levels. In conclusion, pramipexole was able to reduce hydroxyl radical levels induced by 6-OHDA in vivo after local application. This property of pramipexole may be beneficial under conditions of enhanced hydroxyl radical formation in parkinsonian brains and may add to its well known dopamine D(2)-like receptor agonistic effects.

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KW - Animals

KW - Benzothiazoles

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KW - Dopamine Agonists

KW - Hydroxybenzoic Acids

KW - Hydroxyl Radical

KW - Male

KW - Microdialysis

KW - Oxidopamine

KW - Pergolide

KW - Rats

KW - Rats, Wistar

KW - Thiazoles

KW - Pramipexole

KW - 6-Hydroxydopamine

KW - Parkinson’s disease

KW - Salicylate assay

KW - Radical

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DO - 10.1016/S0006-8993(00)02929-2

M3 - Article

C2 - 11074050

VL - 883

SP - 216

EP - 223

JO - Brain Research

JF - Brain Research

SN - 0006-8993

IS - 2

ER -