Oxidative stress and covalent binding have been proposed as possible mechanisms involved in the cytotoxic effects of the parkinsonism-causing compound l-methyl-4-phenyl-I,2,3,6-tetrahydzopyridine (MPTP). However, the toxicity induced by MPTP in isolated fat hepatocytes seems to be relatively independent of oxygen ~adical-induced oxidative stress. Here we demonstrate that MPTP cytotoxicity is no...

Kinetic deuterium isotope effects for the noncompetitive, intermolecular monoamine oxidase B-catalyzed oxidation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to the corresponding 1-methyl-4-phenyl-2,3-dihydropyridinium species MPDP+ were found to be 3.55 on Vmax and 8.01 on Vmax/Km with MPTP-6,6-d2 as the deuterated substrate. Similar values were obtained with MPTP-2,2,6-d4 and MPTP-C...

The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) animal model is a useful tool to study Parkinson's disease (PD) and was used in the present study to investigate the potential beneficial as well as deleterious effects of systemic bone-marrow mononuclear cell (BMMC) or mesenchymal stem cell (BM-MSC) transplantation. MPTP administration resulted in a breakdown of the blood-brain barrier an...

Uncontrolled release of Ca(2+) from the sarcoplasmic reticulum (SR) contributes to the reperfusion-induced cardiomyocyte injury, e.g. hypercontracture and necrosis. To find out the underlying cellular mechanisms of this phenomenon, we investigated whether the opening of mitochondrial permeability transition pores (MPTP), resulting in ATP depletion and reactive oxygen species (ROS) formation, ma...

Paeonol is a major phenolic compound of the Chinese herb, Cortex Moutan, and is known for its antioxidant, anti-inflammatory and antitumor properties. The present study was designed to investigate the therapeutic potential and underlying mechanisms of paeonol on a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid (MPTP/p)-induced mouse model of Parkinson's disease (PD). MPTP (25 mg/kg), f...

Administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to mice and nonhuman primates causes a parkinsonian disorder characterized by a loss of dopamine-producing neurons in the substantia nigra and corresponding motor deficits. MPTP has been proposed to exert its neurotoxic effects through a variety of mechanisms, including inhibition of complex I of the mitochondrial respiratory...

Recent studies provide evidence that phospholipase A2 (PLA2) may play a role in the development of experimental parkinsonism. In this investigation an attempt was made to determine a possible protective effect of quinacrine (QNC), a PLA2 inhibitor on MPTP as well as 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in rodents. For MPTP studies, adult male mice (C57 BL) were treated with MPTP (30...

Ablation of mouse occipital cortex induces precisely timed and uniform p53-modulated and Bax-dependent apoptosis of thalamocortical projection neurons in the dorsal lateral geniculate nucleus (LGN) by 7 d after lesion. We tested the hypothesis that this neuronal apoptosis is initiated by oxidative stress and the mitochondrial permeability transition pore (mPTP). Preapoptotic LGN neurons accumul...

Parkinson disease is a neurological disorder accompanied by degeneration of dopaminergic system and neuronal loss. Recently studies have focused on stem cells therapy, therefore the goal of this study was to investigate the effect of adipose derived stem cells grafting, on locomotion and imbalance in Parkinson model of rats. Twenty-four male Wistar rats weighing 200-250 g were divided into thre...