The role of oxidative stress in I-methyl-4-phenyl1 .2,3,6tetrahydropyridine (MPTPJ-mediated neurotoxicity is as yet unclear and the evidence for generation of oxygen free radicals as a primary event in the neurotoxicity is yet to be demonstrated. The present study was unoertaken to ascertain the potential role of oxidative damage. and the protective role, if any, of the antioxidant, glutathione...

The present experiments sought to determine the implication of estrogen receptors (ERalpha and ERbeta) and their interaction with insulin-like growth factor receptor (IGF-IR) signaling pathways in neuroprotection by estradiol against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity. C57BL/6 male mice were pretreated for 5 days with 17beta-estradiol, an estrogen receptor alpha (ERalp...

To elucidate the toxicological relevance of hepatic aldehyde oxidase (AO) as a detoxification enzyme of 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP), we studied the metabolism and the hepatotoxicity of MPTP in intact rat livers exhibiting different AO activities by using a recirculating perfusion method. In the perfusate during a 90-min recirculation of 1 mM MPTP, the perfused liver fro...

Mitochondria play a central role in both apoptosis and necrosis through the opening of the mitochondrial permeability transition pore (MPTP). This is thought to be formed through a Ca(2+)-triggered conformational change of the adenine nucleotide translocase (ANT) bound to matrix cyclophilin-D and we have now demonstrated this directly by reconstitution of the pure components. Opening of the MPT...

Administration of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to mammals causes damage to the nigrostriatal dopaminergic pathway similar to that observed in Parkinson disease (PD). Reactive oxygen species (ROS) are thought to be involved in the pathogenesis of MPTP-mediated dopaminergic neurodegeneration. To further clarify the role of superoxide anion radical (*O2-) and to study the po...

Since its discovery in the 1970s, the mitochondrial permeability transition (MPT) has been proposed to be a strategic regulator of cell death. Intense research efforts have focused on elucidating the molecular components of the MPT because this knowledge may help to better understand and treat various pathologies ranging from neurodegenerative and cardiac diseases to cancer. In the case of canc...

Dopamine agonists used to manage Parkinsonian motor symptoms have been suggested to be neuroprotective. The study was designed to assess the neuroprotective potential of the D(3)/D(2)/D(1) dopamine receptor agonist rotigotine in the acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned (MPTP) mouse model of Parkinson's disease by measuring mesencephalic degenerating neurons using FluoroJa...

MPTP (1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine) is converted by monoamine oxidase B to its putative toxic metabolite MPP+ (1-methyl-4-phenylpyridinium ion) via MPDP+ (1-methyl-4-phenyl-2,3-dihydropyridinium ion). Both the parent compound and these two major metabolites were toxic to isolated rat hepatocytes with MPDP+ being the most toxic and MPP+ the least effective. MPP+ produced a slight...

INTRODUCTION In Parkinson's disease (PD), compelling data indicate a functional link between adenosine/dopamine receptors and the progression of the neurodegenerative process. The present study was carried out to evaluate the effect of the non-selective adenosine receptor (ADR) antagonist caffeine, as well as the selective antagonists 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), an ADRsA1 antago...