Cabergoline prevents necrotic neuronal death in an in vitro model of oxidative stress.
To study if cabergoline, a long-lasting specific dopamine D2 receptor agonist, has neuroprotective effects against oxidative stress, we exposed (3 h) SH-SY5Y human neuroblastoma cells to tert-butylhydroperoxide (t-BOOH; 500 microM). t-BOOH caused a 42+/-4% neuronal death, which was prevented by cabergoline (2 h before) in a concentration-dependent manner (EC(50): 1.24 microM). This effect was not antagonised by haloperidol (concentration up to 10 microM), and was associated with an increased availability of intracellular GSH contents (+30+/-11%) and a decrease in the membrane lipid peroxidation (-23+/-9%). Our data suggest that cabergoline has neuroprotective effects useful for Parkinson's disease therapy.
Lombardi
Grazia
G
DISCAFF Department, University of Piemonte Orientale, Via Bovio 6, 28100 Novara, Italy. lombardi@pharm.unipmn.it
Varsaldi
Federica
F
Miglio
Gianluca
G
Papini
Maria Grazia
MG
Battaglia
Angelo
A
Canonico
Pier Luigi
PL
D000077465:Cabergoline; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018491:Dopamine Agonists / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D004873:Ergolines / Q000494:pharmacology*; D005609:Free Radicals / Q000378:metabolism; D006220:Haloperidol / Q000494:pharmacology; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008959:Models, Neurological; D009336:Necrosis; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D010300:Parkinson Disease / Q000378:metabolism / Q000517:prevention & control; D017448:Receptors, Dopamine D2 / Q000819:agonists; D014407:Tumor Cells, Cultured; D020122:tert-Butylhydroperoxide / Q000633:toxicity
D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D004873:Ergolines; D005609:Free Radicals; D018696:Neuroprotective Agents; D017448:Receptors, Dopamine D2; D020122:tert-Butylhydroperoxide; D006220:Haloperidol; D000077465:Cabergoline