Neuroprotection by pramipexole against dopamine- and levodopa-induced cytotoxicity

Linglong Zou, Joseph Jankovic, Dominic B. Rowe, Wenjie Xie, Stanley H. Appel, Weidong Le*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

101 Citations (Scopus)

Abstract

Pramipexole, a novel non-ergoline dopamine (DA) agonist, has been applied successfully for treatment of Parkinson's disease (PD). We report here that pramipexole can protect dopaminergic cell line Mes23.5 against dopamine- and levodopa-induced cytotoxicity possibly through a mechanism related to antioxidant activity. In the MES 23.5 cultures, DA and L-DOPA induce a dose- and time-dependent cytotoxicity, as determined by tetrazolium salt and trypan blue assays. Furthermore, an in situ terminal deoxynucleotidyl transferase assay demonstrates that DA-induced cell death is apoptotic. Pretreatment with pramipexole in a concentration range (4-100 μM) significantly attenuates DA- or L-DOPA-induced cytotoxicity and apoptosis, an action which is not blocked by D3 antagonist U-99194 A or D2 antagonist raclopride. Pramipexole also protects MES 23.5 cells from hydrogen peroxide- induced cytotoxicity in a dose-dependent manner. In cell-free system, pramipexole can effectively inhibit the formation of melanin, an end product resulting from DA or L-DOPA oxidation. These results indicate that pramipexole exerts its neuroprotective effect possibly through a mechanism, which is independent of DA receptors but related to antioxidation or scavenging of free radicals (e.g. hydrogen peroxide). As a direct DA agonist and potentially neuroprotective agent, pramipexole remains attractive in the treatment of PD.

Original languageEnglish
Pages (from-to)1275-1285
Number of pages11
JournalLife Sciences
Volume64
Issue number15
DOIs
Publication statusPublished - 5 Mar 1999
Externally publishedYes

Keywords

  • Dopamine
  • L-DOPA
  • Neuroprotection
  • Oxidative stress
  • Pramipexole

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