The protective effect of trihexyphenidyl on the beta-amyloid peptide (25-35)-induced cytotoxicity in PC12 cells.

Key Laboratory of Natural Medicine and Immune Engineering, Henan University, 475001, Kaifeng, China.
Clinical and Experimental Medicine (Impact Factor: 2.83). 12/2010; 10(4):237-43. DOI: 10.1007/s10238-010-0090-9
Source: PubMed

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.

  • [Show abstract] [Hide abstract]
    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. · 2.47 Impact Factor
  • [Show abstract] [Hide abstract]
    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 01/2011; 5:1563-1567.