Neurochemical Mechanisms Underlying Neuroprotective Actions of Bromocriptine, Salicylate, d- and L-Deprenyl in Neurodegeneration caused by MPTP

Abstract

MPTP (l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine) is a potent neurotoxin that causes selective nigral neuronal lesions resulting in severe striatal dopamine (DA) depletion in humans and animals. One of the proposed cellular mechanisms underlying neurodegeneration caused by MPTP is oxidative stress (Adams and Odunze, 1991), following production of reactive oxygen species in the brain (Chiueh et al., 1994). MPTP is converted to its neurotoxic metabolite, MPP⁺, by the action of MAO-B. Inhibitors of this enzyme protect against MPTP-neurotoxicity in animals (Cohen et al., 1984). Deprenyl is used in the treatment of Parkinson’s disease (PD) by virtue of its MAO-B inhibitory action. Deprenyl is suggested to have additional free radical scavenging property (Wu et al., 1994). Bromocriptine (BRC) is a widely used antiparkinsonian drug with potent D2 receptor agonistic action. Strong free radical scavenging action and neuroprotective effect of BRC have been demonstrated recently against MPTP-neurotoxicity (Muralikrishnan and Mohanakumar, 1998). Salicylic acid (SA), the active metabolite of aspirin, is a widely used anti-inflammatory/analgesic agent. SA is used as a hydroxyl radical (·OH) trap in laboratories worldwide. In a recent study, SA rendered protection against MPTP-induced neurotoxicity (Aubin et al., 1998). We demonstrate here the ·OH scavenging action and position influence on brain antioxidant molecules by these drugs as the basic mechanism in protecting the neurons from MPTP insults.