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Fenugreek in Management of Neurological and Psychological Disorders
Published in Dilip Ghosh, Prasad Thakurdesai, Fenugreek, 2022
Rohini Pujari, Prasad Thakurdesai
Furthermore, SFSE-T also exhibited significant protection from 4-phenyl-1,2,3,6-tetrahydro pyridine (MPTP)-induced lesions of brain and motor dysfunction (indicated by speed, distance traveled, number of squares crossed, and spontaneous motor activity scores) in C57BL/6 mice (Gaur et al. 2013). The neurotoxin, MPTP, induces toxic effects on dopaminergic cells, especially in the brain’s substantia nigra pars compacta region (Javitch and Snyder 1984), neuronal impairment and motor dysfunction similar to clinical PD. Neuronal impairment induced by MPTP occurs by converting MPTP to 1-ethyl-4-phenyl-2, 3-dihydropyridium ion (MPP+) by MAO-B in astrocytes (Nicklas, Vyas, and Heikkila 1985). MPP+ produces toxicity specifically in dopaminergic neurons due to its high affinity towards dopamine transporter (DAT) (Javitch and Snyder 1984). The neuroprotection against MPTP-induced neuronal damage by SFSE-T was attributed to the activation of DAT-activating electron transport system of mitochondrial complex-I (NADPH-ubiquinone oxidoreductase I). SFSE-T did not affect the oxotremorine-induced salivation and lacrimation, which showed a lack of anticholinergic effects (Gaur et al. 2013). Therefore, SFSE-T is suggested to provide significant safety benefits compared with many synthetic antiparkinsonian drugs concerning anticholinergic side effects, a major limitation in chronic management of PD (Tuite and Riss 2003).
Homeostasis of Dopamine
Published in Nira Ben-Jonathan, Dopamine, 2020
Several toxic substances which structurally resemble DA are also substrates for DAT and, therefore, can accumulate in DA neurons and cause specific local damage. A prime example is 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), whose neurotoxic properties were serendipitously discovered in the early 1980s when several young drug addicts who were inadvertently exposed to MPTP as a contaminant of heroin, developed an acute form of Parkinsonism [52]. MPTP is first converted by MAO to MPP+ before it is recognized by DAT and is taken up exclusively by dopaminergic neurons. Once inside the neuron, MPP+ accumulates in the mitochondria, where it interferes with the mitochondrial electron transport chain complex I. MPP+ also alters catecholamine metabolism, leading to high oxidative stress and cell death. The selective dopaminergic toxicity of MPP+ has been widely exploited in the efforts to develop cellular and animal models of Parkinson’s disease.
Molecular Aspects of the Activity and Inhibition of the FAD-Containing Monoamine Oxidases
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
A wide variety of amine-containing drugs are also metabolized by MAO, contributing 1% of the enzymatic metabolism of marketed drugs (compared to 95% by the P450 family) (Rendic and Guengerich, 2015). The biotransformation of drugs and other xenobiotics by the amine oxidases in contrast to the P450 family has been reviewed (Benedetti et al., 2001). Metabolism by MAO can also transform a compound into a toxic product. A well-known example is the four electron oxidation of l-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) by MAO to 1-methyl-4-phenylpyridinium (MPP+). The toxic MPP+ is taken up into dopaminergic cells in the substantia nigra and is accumulated into mitochondria where it inhibits NADH oxidation by the respiratory chain, hence preventing ATP production and consequent dopaminergic cell death leading to Parkinson’s disease (Singer and Ramsay, 1990). To avoid such adverse side effects in development of new compounds, computational methods for the prediction of probable metabolic products has been developed based on databases of approved drugs with well-characterized metabolic profiles (Kar and Leszczynski, 2017).
Increased mean perfusion pressure variability is associated with subsequent deterioration of renal function in critically ill patients with central venous pressure monitoring: a retrospective observational study
Published in Renal Failure, 2022
Yudie Peng, Buyun Wu, Changying Xing, Huijuan Mao
Additionally, the association between MPPV and deterioration of renal function may be heterogeneous in patients with cardiac surgery, medical sepsis and others. Critically ill patients with medical sepsis are characterized with endothelial dysfunction [38]. Thus, the same rise and fall in MPP may lead to greater fluctuation of renal blood flow compared to those diseases without marked endothelial dysfunction. And for patients undergoing cardiac surgery, they presented with decreased perfusion pressure characterized by renal venous congestion [39]. The correlation between absolute level of MPP and the deterioration of renal function may be more significant [40]. After adjusting for TWA-MPP, the correlation between MPPV and the deterioration of renal function weakened. In patients after abdominal surgery, intra-abdominal pressure may have a greater effect on renal perfusion [41]. However, our study excluded patients with acute compartment syndrome, and the number of patients undergoing abdominal surgery was limited, so they were not discussed separately.
Protective role of selenium on MPP+ and homocysteine-induced TRPM2 channel activation in SH-SY5Y cells
Published in Journal of Receptors and Signal Transduction, 2022
Kenan Yıldızhan, Mustafa Nazıroğlu
Human neuroblastoma SH-SY5Y cells, especially in vitro neuronal cell models, have been studied extensively in relation to, for example, Alzheimer's and PDs [12]. MPP is a neurotoxic metabolite derived from MPTP used to induce PD in experimental models. MPP is known to cause neuronal toxicity by inhibiting mitochondrial complex I and NAD(H)-related oxidation of the electron transport chain [13]. MPP influences dopamine release processes and the subsequent formation of free radicals [14]. In a study, the SH-SY5Y cells induced by MPP have been reported to reduce apoptosis and cytotoxicity with antioxidant properties of tectorigenin [5]. There are studies showing increased intracellular reactive oxygen species (ROS) and Ca2+ in SH-SY5Y cells induced by MPP [15]. ROS also directly induce Ca2+ influx into the cytosol by activation of ROS sensible Ca2+ permeable channels in the cell membrane. Therefore, this mechanism generates a cycle that gradually increases Ca2+ concentration that leads to cell death [16].
Evaluation of cell protection by Psephellus pyrrhoblepharus (Boiss.) Wagenitz extracts in MPP+-induced dopaminergic cell damage
Published in Drug and Chemical Toxicology, 2022
Pelin Taştan, Güliz Armagan, Taner Dağcı, Bijen Kıvçak
MPP+ is a well-known neurotoxin that interacts with ‘complex I’ in the electron transport chain in the substantia nigra causing dopaminergic cell death following being taken into the cell by the dopamine transporter (Przedborski and Vila 2003). MPP+ triggers the production of free radicals and increases cell death, thereby inducing a syndrome resembling Parkinson’s disease (Rascol et al.2003). This neurotoxin produces neuronal degeneration mediated by oxidative stress, mitochondrial dysfunction, and apoptosis in the human neuroblastoma cell line SH-SY5Y (Singer and Ramsay 1990, Wu et al.2009). In this study, we aimed to evaluate the potential neuroprotective effects of the n-hexane, chloroform, and methanol: water (1:1) extracts of P. pyrrhoblepharus in an MPP+-induced dopaminergic cell death model suggesting a potential use of these extracts in oxidative stress-related diseases.