The protective effect of trihexyphenidyl on the beta-amyloid peptide (25-35)-induced cytotoxicity in PC12 cells
ABSTRACT In the development and progression of Alzheimer's disease (AD), β-amyloid peptide (Aβ) that induced cytotoxicity containing apoptosis and excess production of reactive oxygen species (ROS) is considered as a causal role. The aim of present study is to investigate the protective effect of Trihexyphenidyl (THY) on Aβ(25-35)-induced cytotoxicity in cultured rat pheochromocytoma (PC12) cells. In this report, the cell survival was measured by MTT assay, the enzyme activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX), the contents of lipid peroxidation products malondialdehyde (MDA) and ROS in the cells were determined. Acridine orange (AO) was used to observe the morphological characteristic of apoptotic cells. Mitochondrial membrane potential in PC12 cells were monitored by fluorospectrophotometer combining with Rh123. As a cell permeable fluorescent probe, Fura-2/AM was employed to detect intracellular [Ca(2+)]. The results showed that after incubation with Aβ(25-35) (10 μM) for 24 h, there were decreased changes in cell viability, SOD, and GSH-PX activity as well as mitochondrial membrane potential, in contrast, the levels of [Ca(2+)](i), ROS, and MDA were increased, THY significantly attenuated all the changes induced by Aβ(25-35), indicating that THY exhibited protective effect against Aβ(25-35)-induced cytotoxicity, which may represent the cellular mechanisms of the action.
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ABSTRACT: Despite the crucial role of redox active metals like copper and iron in central biological reactions, their elevated levels are involved in the pathogenesis of Alzheimer's Disease (AD). Similarly reactive oxygen/nitrogen species (ROS/RNS) produced during normal metabolic activities, specifically oxidative phosphorylation of the cell, are scavenged by antioxidant enzymes like superoxide dismutase (SOD), catalase but impaired metabolic pathways tend to generate elevated levels of these ROS/RNS. Iron, copper, and zinc are some of the metals, which intensify this process and contribute for the pathogenesis of AD. This review summarizes the mechanism of ROS/RNS production and their role in lipid peroxidation. The factors, which make brain vulnerable for lipid peroxidation, have been discussed. It also focuses on possible treatment options and future directions.Acta Neurologica Scandinavica 02/2011; 124(5):295-301. DOI:10.1111/j.1600-0404.2010.01483.x · 2.40 Impact Factor
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ABSTRACT: Ethanol has long been demonstrated to trigger cell apoptosis in the central nervous system. The over-production of reactive oxygen species (ROS) is considered as one of the most important mechanisms involving in the apoptosis caused by ethanol. Ginkgolide B (GB), which was widely used as a monomer of traditional Chinese medicine, was reported to scavenge free radicals in endothelial cells and smooth muscle cells. But whether GB can prevent ethanol-induced neurotoxicity is still unknown. The aim of this study was to investigate effects of GB on ethanol-induced cytotoxicity, oxidative stress and apoptosis and explore potential protective molecular mechanism of GB. It was found that GB inhibited cell injury and apoptosis in a dose-dependent manner in ethanol-treated PC12 cells by MTT and LDH assays. It was also found that activities of caspase-3 increased by ethanol were mostly abrogated by GB. Further, GB decreased the production of ROS and subsequent over-production of lipid peroxides. A significant increase of alcohol dehydrogenase (ADH) and CYP2E1 enzyme activity was found in the ethanol-exposed PC12 cells as compared to controls. However, GB pretreatment did not significantly affect ethanol-induced ADH and CYP2E1 activities. Quantitative real-time PCR and Western blot analysis demonstrated that ethanol treatment resulted in a significant increase in mRNA and protein expression of NADPH oxidases, which are main oxidases producing ROS in neurons. Moreover, expression and activities of NADPH oxidases were down-regulated by GB. These results indicate that ethanol-induced neurotoxicity is ameliorated by GB mainly through regulating expression and activity of NADPH oxidases.Toxicology 06/2011; 287(1-3):124-30. DOI:10.1016/j.tox.2011.06.006 · 3.62 Impact Factor
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ABSTRACT: This paper analyzes the problems of ecotourism and proposes some suggestions according to the behaviors of travel agency, tourist and eco-scenic spot. From a macro perspective, the government should tax the eco-scenic spots in order to solve the externalities of ecotourism. Establishing the return model between the travel agency and eco-scenic spot is useful to restrict travel agency behavior. This paper constructs the ecotourism models based on capital and tax aiming at harmonious development and proposes a series of recommendations for the government and eco-scenic spots.Energy Procedia 12/2011; 5:1563-1567. DOI:10.1016/j.egypro.2011.03.267