2003 Progress Report: Studies of Oxidant MechanismsEPA Grant Number: R827353C011
Subproject: this is subproject number 011 , established and managed by the Center Director under grant R827353
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: EPA Harvard Center for Ambient Particle Health Effects
Center Director: Koutrakis, Petros
Title: Studies of Oxidant Mechanisms
Investigators: Gonzalez-Flecha, Beatriz
Current Investigators: Godleski, John J. , Gonzalez-Flecha, Beatriz
Institution: Harvard University
EPA Project Officer: Chung, Serena
Project Period: June 1, 1999 through May 31, 2005 (Extended to May 31, 2006)
Project Period Covered by this Report: June 1, 2002 through May 31, 2003
RFA: Airborne Particulate Matter (PM) Centers (1999) RFA Text | Recipients Lists
Research Category: Air Quality and Air Toxics , Particulate Matter , Air
The objective of this research project is to confirm the role of oxidants in the inflammatory response to concentrated ambient particles (CAPs) in adult rats.
This is one of 10 projects funded by the Center. The progress for the other nine projects is reported separately (see reports for R827353C001 through R827353C010.
Dr. González-Flecha and her colleagues have completed and published a study confirming the role of oxidants in the inflammatory response to CAPs in adult rats (Rhoden, et al., 2004). The experimental protocol included exposures to filtered air (Sham) or CAP aerosols (CAPs, 5 hours exposure, average mass concentration: 1,100 ± 300 µg/m3) in the presence or absence of 50 mg/kg N-acetylcysteine (NAC). Bronchoalveolar lavage (BAL), tissue, and blood in samples were collected 24 hours after exposure. The results of this study show a dramatic increase in polymorphonuclear leukocyte (PMN) number in BAL as a result of CAP exposures. This increase was mediated by oxidants because preadministration of NAC effectively prevented PMN influx into the lung. Additional recent data support our hypotheses that CAPs promote oxidant-mediated cardiac dysfunction and that sympathetic activation after CAP deposition in the lung is critical for CAP cardiotoxicity. Adult Sprague-Dawley rats were treated with the 1-adrenoreceptor antagonist atenolol or saline prior to exposure to urban ambient particles (UAPs, Standard Reference Material 1649, 750 µg/kg). Thirty minutes after UAP instillation, the animals were anesthetized and assayed immediately for cardiac levels of oxidants (in situ chemiluminescence). Tissue samples were collected and assayed for edema. Intratracheal instillation of UAPs led to significant increases in heart oxidants and edema. -blockage by atenolol effectively prevented cardiac oxidative stress and damage. These observations were confirmed in a model of inhalation exposure to CAPs. Studies will continue in this important area in the coming year.
We will continue to confirm the role of oxidants in the inflammatory response to CAPs in adult rats. In addition, we will continue to collect and assay tissue samples for edema as well as evaluate our observations in the coming year.
Journal Articles on this Report : 1 Displayed | Download in RIS Format
|Other subproject views:||All 3 publications||3 publications in selected types||All 3 journal articles|
|Other center views:||All 200 publications||198 publications in selected types||All 197 journal articles|
||Rhoden CR, Lawrence J, Godleski JJ, Gonzalez-Flecha B. N-Acetylcysteine prevents lung inflammation after short-term inhalation exposure to concentrated ambient particles. Toxicological Sciences 2004;79(2):296-303.||
Supplemental Keywords:exposure, health effects, susceptibility, biology, toxicology, environmental chemistry, air pollutants, air pollution, air quality, ambient air, ambient air quality, ambient particle health effects, ambient particles, animal inhalation study, exposure assessment, biological mechanism, biological response, cardiopulmonary, cardiopulmonary response, cardiovascular disease, chemical exposure, environmental health hazard, exposure and effects, health risks, human exposure, human health, human health effects, human health risk, human susceptibility, inhalation, inhalation toxicology, inhaled particles, particle exposure, particulate exposure, particulates, pulmonary, pulmonary disease, respiratory, respiratory disease., RFA, Health, Scientific Discipline, Air, particulate matter, Toxicology, Environmental Chemistry, Epidemiology, Risk Assessments, Environmental Microbiology, Environmental Monitoring, tropospheric ozone, Molecular Biology/Genetics, Biology, Environmental Engineering, ambient air quality, particulates, chemical exposure, human health effects, ambient air monitoring, concentrated ambient particulates (CAPs), ambient air, ambient measurement methods, pulmonary disease, developmental effects, epidemelogy, respiratory disease, air pollution, particle exposure, biological mechanism , human exposure, inhalation, pulmonary, particulate exposure, ambient particle health effects, inhalation toxicology, oxidant mechanisms, measurement methods , cardiovascular disease, human health risk, respiratory, genetic susceptibility
Progress and Final Reports:Original Abstract
Main Center Abstract and Reports:R827353 EPA Harvard Center for Ambient Particle Health Effects
Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R827353C001 Assessing Human Exposures to Particulate and Gaseous Air Pollutants
R827353C002 Quantifying Exposure Error and its Effect on Epidemiological Studies
R827353C003 St. Louis Bus, Steubenville and Atlanta Studies
R827353C004 Examining Conditions That Predispose Towards Acute Adverse Effects of Particulate Exposures
R827353C005 Assessing Life-Shortening Associated with Exposure to Particulate Matter
R827353C006 Investigating Chronic Effects of Exposure to Particulate Matter
R827353C007 Determining the Effects of Particle Characteristics on Respiratory Health of Children
R827353C008 Differentiating the Roles of Particle Size, Particle Composition, and Gaseous Co-Pollutants on Cardiac Ischemia
R827353C009 Assessing Deposition of Ambient Particles in the Lung
R827353C010 Relating Changes in Blood Viscosity, Other Clotting Parameters, Heart Rate, and Heart Rate Variability to Particulate and Criteria Gas Exposures
R827353C011 Studies of Oxidant Mechanisms
R827353C012 Modeling Relationships Between Mobile Source Particle Emissions and Population Exposures
R827353C013 Toxicological Evaluation of Realistic Emissions of Source Aerosols (TERESA) Study
R827353C014 Identifying the Physical and Chemical Properties of Particulate Matter Responsible for the Observed Adverse Health Effects
R827353C015 Research Coordination Core
R827353C016 Analytical and Facilities Core
R827353C017 Technology Development and Transfer Core