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LACK OF EFFECT OF AGE AND ANTIOXIDANT DEPLETION ON RESPIRATORY RESPONSES TO CONCENTRATED AMBIENT PARTICULATES (CAPS) IN RATS
Dye, J A., L. C. Walsh, C. L. Hayes, J H. Richards, D. W. Winsett, U P. Kodavanti, AND W P. Watkinson. LACK OF EFFECT OF AGE AND ANTIOXIDANT DEPLETION ON RESPIRATORY RESPONSES TO CONCENTRATED AMBIENT PARTICULATES (CAPS) IN RATS. Presented at PM: Atmospheric Sciences, Exposure and the Fourth Colloquium on PM and Human Health, Pittsburgh, PA, March 31-April 4, 2003.
2003 AAR PM Meeting
Particulate Matter: Atmospheric Sciences,
Exposure and the Fourth Colloquium on PM and Human Health
LACK OF EFFECT OF AGE AND ANTIOXIDANT DEPLETION ON RESPIRATORY RESPONSES TO CONCENTRATED AMBIENT PARTICULATES (CAPs) IN RATS. JA Dye, LC Walsh, CL Hayes,* JH Richards, DW Winsett, UP Kodavanti, WP Watkinson. US EPA, ORD, NHEERL, ETD, Pulmonary Toxicology Branch, RTP, NC and *SEEP, RTP, NC.
Metal-mediated generation of reactive oxygen species (ROS) and oxidative stress have been proposed as one of the main mechanisms for emission-source PM toxicity. Oxidative stress has also been implicated in aging and in the pathogenesis of asthma. Asthma, an inflammatory air-ways disease has become an urgent health problem; with elderly asthmatics experiencing some of the highest mortality rates of any age group. Thus, we evaluated whether antioxidant re-sponses were important in the respiratory effects associated with ambient PM exposure. In study 1, 12-wk Sprague Dawley (CD) rats were exposed to CAPs from central North Carolina (NC). Buthionine sulfoximine (BSO) was administered systemically to deplete lung glutathione prior to and during air or CAPs nose-only exposure (4h/day x 2 days). Airway re-sponsiveness (AR) to methacholine was also assessed. In study 2, young adult (10-wk) and geriatric (15-mo) spontaneously hypertensive (SH) and WKY (background strain) rats were ex-posed to air or CAPs in a whole-body chamber (4h/day x 2 days). In addition to hypertension, SH rats have neutrophilic lung inflammation seemingly related to antioxidant deficits. Lung, blood, bronchoal-veolar, and nasal lavage fluid (BALF, NALF) samples were collected 20h later. In study 1, PM cham-ber concentrations were 150-800 ?g/M^3. Although BSO treatment depleted lung glutathione levels by 50%, neither saline- nor BSO-treated rats exhibited increased AR af-ter CAPs exposure. Likewise, regardless of antioxidant status, neither group developed signifi-cant lung injury / inflammation. In study 2, PM concentrations were 1400-1800 ?g/M^3. Data indicated that for many BALF indices, relative to WKY rats, SH rats had higher levels (e.g., albu-min, TP, lysozyme, cytokines) and cell counts (due to more macro-phages). While the magnitude of these differences increased with age, relative to these changes, CAPs-induced effects in geriatric rats were negligible. In young rats, CAPs expo-sure was associated with minor increases in BALF GGT and trends towards increased albumin, TP, and neutrophils. In summary, depletion of lung antioxidant levels failed to predispose CD rats to developing greater lung changes after exposure to summertime CAPs from the NC airshed. Similarly, although geriatric SH rats had greater changes in BALF biochemical and inflammatory indices, advanced age alone did not predispose these rats to de-veloping greater CAPs-induced lung injury or inflammation. (Abstract does not reflect USEPA policy.)
Record Details:Record Type: DOCUMENT (PRESENTATION/ABSTRACT)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY
EXPERIMENTAL TOXICOLOGY DIVISION
PULMONARY TOXICOLOGY BRANCH