Investigation of the effects of triciclic psychodrugs against the oxidative stress in Neuro-2A cells

• Grant number: 12/14493-6
• Support Opportunities: Scholarships in Brazil - Master
• Start date: October 01, 2012
• End date: January 31, 2014
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Tiago Rodrigues
• Grantee: Gemima Samara Bezerra Vanderley
• Host Institution: Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil

Abstract

The pathogenesis of neuronal disorders has been associated to the cell death with involvement of oxidative stress. The increase in the mitochondrial free radical production, persistent changes in the mitochondrial integrity (mitochondrial permeability transition, MPT) and mitochondrial depolarization seem to play central role. In this project it will be studied the effects of three psychotropic drugs, imipramine, chlorpromazine, and thioridazine on the oxidative stress in Neuro-2A cells, a neuronal model. It is intended primarily to characterize the hydrogen peroxide induced oxidative stress in these cells and then evaluate cell response when exposed to the drugs under oxidative stress conditions. There is a controversy about the cytoprotective / cytotoxic activity of these drugs in these conditions. It will be evaluated the cell viability and parameters related to the cellular redox state as the oxidation state of cellular proteins and lipids, antioxidants content and reactive oxygen species generation. It will also be investigated the molecular mechanisms that account to the observed effects including the involvement of mitochondria, since this is the major source and target of oxygen reactive species.