Pergolide scavenges both hydroxyl and nitric oxide free radicals in vitro and inhibits lipid peroxidation in different regions of the rat brain

Abstract

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.

Isolation of a diterpenoid substance with potent neuroprotective activity from fetal calf serum

“…NO ⅐ and hydroxyl radical ( ⅐ OH) were detected by ESR spectrometry in an in vitro system generating NO ⅐ and ⅐ OH as described (21). The NO ⅐ donor 3-(2-hydroxy-1-methyl-2-nitrosohydrazino)-N-methyl-1-propanamin (NOC7; 5 M) and 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazole-1-oxyl 3-oxide (carboxy-PTIO; 5 M), as a spin-trapping agent, were used for detection of NO ⅐ .…”

Antiparkinsonian Drugs and Their Neuroprotective Effects.

“…3,4) Similar phenomena were observed in MPTP-treated animals used as models of parkinsonism. 27,70) Recent studies have suggested that ergot-derivative D 2 -receptor agonists, such as bromocriptine, pergolide and cabergoline, directly scavenge hydroxyl and/or nitric oxide (NO) radicals [71][72][73][74] and inhibit lipid peroxidation. 75,76) Ropinirole, a non-ergot D 2 -receptor agonist, also scavenges free radicals and suppresses lipid peroxidation.…”

Pramipexole Protects Spinal Motor Neuron Death Against Glutamate-Induced Neurotoxicity

“…Several studies have reported antioxidation or scavenging of free radicals for dopamine agonists, including apomorphine, bromocriptine, pergolide, PPX and ropinirole in cell cultures and animal model of injury of substantia nigra [14][15][16][17][18][19][20][21][22][23]. Preincubation of primary mesencephalic neuronal cultures with bromocriptine or quinpirole has provided neuroprotection against glutamate-induced neurotoxicity [24].…”