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 journalArticlepeer-review

65 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

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)

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