Pergolide scavenges both hydroxyl and nitric oxide free radicals in vitro and inhibits lipid peroxidation in different regions of the rat brain.
The free radical hypothesis for the pathogenesis and/or progression of Parkinson's disease (PD) has gained wide acceptance in recent years. Although it is clear that dopamine (DA) agonists cannot completely replace levodopa therapy, they can be beneficial early in the course of PD by reducing the accumulation of DA which undergoes auto-oxidation and generates cytotoxic free radicals. In the present study we demonstrate that pergolide, a widely used DA agonist, has free radical scavenging and antioxidant activities. Using a direct detection system for nitric oxide radical (NO.) by electron spin resonance (ESR) spectrometry in an in vitro .NO-generating system, we examined the quenching effects of pergolide on the amount of NO. generated. Pergolide dose-dependently scavenged NO.. In the competition assay, the IC50 value for pergolide was estimated to be about 30 microM. Pergolide also dose-dependently attenuated the hydroxyl radical (.OH) signal in an in vitro FeSO4-H2O2 ESR system with an approximate IC50 value of 300 microM. Furthermore, this agent significantly inhibited phospholipid peroxidation of rat brain homogenates in in vitro experiments and after repeated administration (0.5 mg/kg/24 h, i.p. for 7 days). Our findings suggest a neuroprotective role for pergolide on dopaminergic neurons due to its free radical scavenging and antioxidant properties.
Gómez-Vargas
M
M
Department of Neuroscience, Institute of Molecular and Cellular Medicine, Okayama University Medical School, Okayama, Japan. gomezmar@cc.okayama-u.ac.jp
Nishibayashi-Asanuma
S
S
Asanuma
M
M
Kondo
Y
Y
Iwata
E
E
Ogawa
N
N
D000818:Animals; D001565:Benzoates; D001923:Brain Chemistry / Q000187:drug effects*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D003497:Cyclic N-Oxides; D018491:Dopamine Agonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004578:Electron Spin Resonance Spectroscopy; D016166:Free Radical Scavengers / Q000494:pharmacology; D006179:Gyrus Cinguli / Q000187:drug effects / Q000378:metabolism; D017665:Hydroxyl Radical / Q000378:metabolism*; D007093:Imidazoles; D015227:Lipid Peroxidation / Q000502:physiology*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D010084:Oxidation-Reduction; D010479:Pergolide / Q000494:pharmacology*; D010743:Phospholipids / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism; D013687:Telencephalon / Q000187:drug effects / Q000378:metabolism
D001565:Benzoates; D003497:Cyclic N-Oxides; D018491:Dopamine Agonists; D016166:Free Radical Scavengers; D007093:Imidazoles; D010743:Phospholipids; C079393:1,3-dihydroxy-4,4,5,5-tetramethyl-2-(4-carboxyphenyl)tetrahydroimidazole; D010479:Pergolide; D009569:Nitric Oxide; D017665:Hydroxyl Radical; C069977:2,2-dimethyl-5-hydroxy-1-pyrrolidinyloxy