Grantee Research Project Results
2003 Progress Report: Studies of Oxidant Mechanisms
EPA Grant Number: R827353C011Subproject: 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: Health Effects Institute (2015 - 2020)
Center Director: Greenbaum, Daniel S.
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
Objective:
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.
Progress Summary:
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.
Future Activities:
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 207 publications | 205 publications in selected types | All 204 journal articles |
| Type | Citation | ||
|---|---|---|---|
|
|
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. |
R827353 (Final) R827353C011 (2003) R827353C011 (Final) |
Exit Exit Exit |
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, particulates, chemical exposure, ambient air quality, human health effects, ambient air monitoring, concentrated ambient particulates (CAPs), pulmonary disease, developmental effects, epidemelogy, respiratory disease, ambient air, ambient measurement methods, air pollution, particle exposure, biological mechanism , particulate exposure, pulmonary, inhalation, ambient particle health effects, human exposure, inhalation toxicology, oxidant mechanisms, measurement methods , respiratory, cardiovascular disease, genetic susceptibility, human health risk
Relevant Websites:
https://cfserver.hsph.harvard.edu/cfdocs/eer/epa/ Exit
Progress and Final Reports:
Original AbstractMain Center Abstract and Reports:
R827353 Health Effects Institute (2015 - 2020) 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
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.