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Analysis of Oxidative Stress in Mice Exposed to Concentrated Atmospheric Particulates and Treated with Carbamic Acid, Urethane and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)

Grant number: 13/02400-6
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): May 01, 2013
Effective date (End): April 30, 2014
Field of knowledge:Health Sciences - Pharmacy - Toxicological Analysis
Principal Investigator:Tania Marcourakis
Grantee:Michelle Francini Del Rigo Santos Dias
Home Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Epidemiological studies have associated extended exposure to urban particulate matter (PM) with the development of lung cancer: physical characteristics of the PM, such as size and surface, are crucial to its ability to trigger biological effects. The most important pathophysiological mechanism for triggering lung tumors is oxidative stress, which form reactive oxygen species (ROS), which participate in reactions leading to lipid peroxidation and, consequently, to cell damage. A response model has been developed to explain the process of oxidative stress. Initially, when the oxidative stress is relatively low, several transcription factors induce the production of a series of antioxidants and detoxification enzymes including catalase, superoxide dismutase and glutathione S-transferase, which eliminate ROS, preventing the PM exposure to cause adverse biological effects. In a second phase, when the protective effect of antioxidant response fails, a pro-inflammatory situation occurs and cytotoxic effects appear. Thus, this study aims to examine oxidative stress in different organs and tissues (erythrocytes, plasma, lung and central nervous system) in mice exposed to concentrated particulate matter originated from the city of São Paulo, from the quantification of antioxidant enzymes GPx, GST, GR and SOD, and quantification of an indicator of lipid peroxidation, MDA, allowing the establishment of a relationship of their levels with oxidative stress and the relation of the latter with the exposure to particulate matter in the city of São Paulo.