The dopamine agonist cabergoline provides neuroprotection by activation of the glutathione system and scavenging free radicals

Michiyo Yoshioka, Ken Ichi Tanaka, Ikuko Miyazaki, Naoko Fujita, Youichirou Higashi, Masato Asanuma, Norio Ogawa

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

Free radicals are involved in the pathogenesis and/or progression of Parkinson's disease (PD). Several ergot derivative dopamine (DA) agonists have been reported to scavenge free radicals in vitro and to show a neuroprotective effect in vivo. We investigated the in vitro free radical scavenging and antioxidant activities of cabergoline, a long-acting ergot DA agonist, as well as its ability to activate glutathione (GSH), catalase (Cat) and superoxide dismutase (SOD) activating effects and its in vivo neuroprotective properties against 6-hydroxydopamine (6-OHDA) intracerebroventricularly (i.c.v.) in mice. The striatal DA turnover induced by i.c.v. injection of 6-OHDA was completely normalized by pretreatment with cabergoline. Moreover, cabergoline scavenged free radicals in vitro and significantly reduced lipid peroxidation in vitro and in vivo. Furthermore, daily administration of cabergoline to mice significantly increased striatal GSH levels by activation of RNA expressions of GSH-related enzymes, although striatal Cat and SOD activities did not change. In addition, our present results suggest that repeated administration of cabergoline attenuates both 6-OHDA-induced nigrostriatal DAergic dysfunction and DA neuronal cell death, since cabergoline also had a neuroprotective effect in the immunohistochemical experiment. In conclusion, our findings indicate that the multiple antioxidant mechanisms of cabergoline, such as activation of the GSH system and the direct free radical scavenging activity, may explain the neuroprotective effect of this ergot DA agonist.

Original languageEnglish
Pages (from-to)259-267
Number of pages9
JournalNeuroscience Research
Volume43
Issue number3
DOIs
Publication statusPublished - 2002

Fingerprint

Dopamine Agonists
Free Radicals
Glutathione
Oxidopamine
Corpus Striatum
Neuroprotective Agents
Catalase
Superoxide Dismutase
Dopamine
Antioxidants
Neuroprotection
cabergoline
Lipid Peroxidation
Parkinson Disease
Cell Death
RNA
Injections
In Vitro Techniques
Enzymes

Keywords

  • 6-Hydroxydopamine
  • Antioxidant
  • Dopamine D2 receptor
  • Dopaminergic neurons
  • Nigrostriatal pathway
  • Parkinson's disease

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

The dopamine agonist cabergoline provides neuroprotection by activation of the glutathione system and scavenging free radicals. / Yoshioka, Michiyo; Tanaka, Ken Ichi; Miyazaki, Ikuko; Fujita, Naoko; Higashi, Youichirou; Asanuma, Masato; Ogawa, Norio.

In: Neuroscience Research, Vol. 43, No. 3, 2002, p. 259-267.

Research output: Contribution to journalArticle

Yoshioka, Michiyo ; Tanaka, Ken Ichi ; Miyazaki, Ikuko ; Fujita, Naoko ; Higashi, Youichirou ; Asanuma, Masato ; Ogawa, Norio. / The dopamine agonist cabergoline provides neuroprotection by activation of the glutathione system and scavenging free radicals. In: Neuroscience Research. 2002 ; Vol. 43, No. 3. pp. 259-267.
@article{599bd80487fb4613bdf5119c88410dc0,
title = "The dopamine agonist cabergoline provides neuroprotection by activation of the glutathione system and scavenging free radicals",
abstract = "Free radicals are involved in the pathogenesis and/or progression of Parkinson's disease (PD). Several ergot derivative dopamine (DA) agonists have been reported to scavenge free radicals in vitro and to show a neuroprotective effect in vivo. We investigated the in vitro free radical scavenging and antioxidant activities of cabergoline, a long-acting ergot DA agonist, as well as its ability to activate glutathione (GSH), catalase (Cat) and superoxide dismutase (SOD) activating effects and its in vivo neuroprotective properties against 6-hydroxydopamine (6-OHDA) intracerebroventricularly (i.c.v.) in mice. The striatal DA turnover induced by i.c.v. injection of 6-OHDA was completely normalized by pretreatment with cabergoline. Moreover, cabergoline scavenged free radicals in vitro and significantly reduced lipid peroxidation in vitro and in vivo. Furthermore, daily administration of cabergoline to mice significantly increased striatal GSH levels by activation of RNA expressions of GSH-related enzymes, although striatal Cat and SOD activities did not change. In addition, our present results suggest that repeated administration of cabergoline attenuates both 6-OHDA-induced nigrostriatal DAergic dysfunction and DA neuronal cell death, since cabergoline also had a neuroprotective effect in the immunohistochemical experiment. In conclusion, our findings indicate that the multiple antioxidant mechanisms of cabergoline, such as activation of the GSH system and the direct free radical scavenging activity, may explain the neuroprotective effect of this ergot DA agonist.",
keywords = "6-Hydroxydopamine, Antioxidant, Dopamine D2 receptor, Dopaminergic neurons, Nigrostriatal pathway, Parkinson's disease",
author = "Michiyo Yoshioka and Tanaka, {Ken Ichi} and Ikuko Miyazaki and Naoko Fujita and Youichirou Higashi and Masato Asanuma and Norio Ogawa",
year = "2002",
doi = "10.1016/S0168-0102(02)00040-8",
language = "English",
volume = "43",
pages = "259--267",
journal = "Neuroscience Research",
issn = "0168-0102",
publisher = "Elsevier Ireland Ltd",
number = "3",

}

TY - JOUR

T1 - The dopamine agonist cabergoline provides neuroprotection by activation of the glutathione system and scavenging free radicals

AU - Yoshioka, Michiyo

AU - Tanaka, Ken Ichi

AU - Miyazaki, Ikuko

AU - Fujita, Naoko

AU - Higashi, Youichirou

AU - Asanuma, Masato

AU - Ogawa, Norio

PY - 2002

Y1 - 2002

N2 - Free radicals are involved in the pathogenesis and/or progression of Parkinson's disease (PD). Several ergot derivative dopamine (DA) agonists have been reported to scavenge free radicals in vitro and to show a neuroprotective effect in vivo. We investigated the in vitro free radical scavenging and antioxidant activities of cabergoline, a long-acting ergot DA agonist, as well as its ability to activate glutathione (GSH), catalase (Cat) and superoxide dismutase (SOD) activating effects and its in vivo neuroprotective properties against 6-hydroxydopamine (6-OHDA) intracerebroventricularly (i.c.v.) in mice. The striatal DA turnover induced by i.c.v. injection of 6-OHDA was completely normalized by pretreatment with cabergoline. Moreover, cabergoline scavenged free radicals in vitro and significantly reduced lipid peroxidation in vitro and in vivo. Furthermore, daily administration of cabergoline to mice significantly increased striatal GSH levels by activation of RNA expressions of GSH-related enzymes, although striatal Cat and SOD activities did not change. In addition, our present results suggest that repeated administration of cabergoline attenuates both 6-OHDA-induced nigrostriatal DAergic dysfunction and DA neuronal cell death, since cabergoline also had a neuroprotective effect in the immunohistochemical experiment. In conclusion, our findings indicate that the multiple antioxidant mechanisms of cabergoline, such as activation of the GSH system and the direct free radical scavenging activity, may explain the neuroprotective effect of this ergot DA agonist.

AB - Free radicals are involved in the pathogenesis and/or progression of Parkinson's disease (PD). Several ergot derivative dopamine (DA) agonists have been reported to scavenge free radicals in vitro and to show a neuroprotective effect in vivo. We investigated the in vitro free radical scavenging and antioxidant activities of cabergoline, a long-acting ergot DA agonist, as well as its ability to activate glutathione (GSH), catalase (Cat) and superoxide dismutase (SOD) activating effects and its in vivo neuroprotective properties against 6-hydroxydopamine (6-OHDA) intracerebroventricularly (i.c.v.) in mice. The striatal DA turnover induced by i.c.v. injection of 6-OHDA was completely normalized by pretreatment with cabergoline. Moreover, cabergoline scavenged free radicals in vitro and significantly reduced lipid peroxidation in vitro and in vivo. Furthermore, daily administration of cabergoline to mice significantly increased striatal GSH levels by activation of RNA expressions of GSH-related enzymes, although striatal Cat and SOD activities did not change. In addition, our present results suggest that repeated administration of cabergoline attenuates both 6-OHDA-induced nigrostriatal DAergic dysfunction and DA neuronal cell death, since cabergoline also had a neuroprotective effect in the immunohistochemical experiment. In conclusion, our findings indicate that the multiple antioxidant mechanisms of cabergoline, such as activation of the GSH system and the direct free radical scavenging activity, may explain the neuroprotective effect of this ergot DA agonist.

KW - 6-Hydroxydopamine

KW - Antioxidant

KW - Dopamine D2 receptor

KW - Dopaminergic neurons

KW - Nigrostriatal pathway

KW - Parkinson's disease

UR - http://www.scopus.com/inward/record.url?scp=0036018104&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036018104&partnerID=8YFLogxK

U2 - 10.1016/S0168-0102(02)00040-8

DO - 10.1016/S0168-0102(02)00040-8

M3 - Article

C2 - 12103444

AN - SCOPUS:0036018104

VL - 43

SP - 259

EP - 267

JO - Neuroscience Research

JF - Neuroscience Research

SN - 0168-0102

IS - 3

ER -