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Susceptibility of adult and senescent brown norway rats to repeated ozone exposure: An assessment of behavior, serum biochemistry and cardiopulmonary function
Gordon, C., K. Jarema, J. Lehmann, A. Ledbetter, M. Schladweiler, Judy Schmid, W. Ward, U. Kodavanti, A. Nyska, AND R. Macphail. Susceptibility of adult and senescent brown norway rats to repeated ozone exposure: An assessment of behavior, serum biochemistry and cardiopulmonary function. INHALATION TOXICOLOGY. Taylor & Francis, Inc., Philadelphia, PA, 25(3):141-59, (2013).
The aged are considered a susceptible population to air pollutants and other environmental toxicants. This study was developed to perform a comprehensive assessment using cardiovascular, pulmonary, behavioral, and serum biomarker endpoints to compare the susceptibility of young and aged rats to episodic ozone exposure. It was found that young animals show a more rapid and severe respiratory dysfunction as results of their ability to mount a rapid inflammatory response following ozone. Aged rats eventually show declines in ventilatory function but lag behind the younger animals. Serum biomarkers of age and ozone exposure were identified. The data from this study will be useful in the refinement of guidelines of exposure to ozone and other air pollutants while factoring in age as critical aspect of susceptibility.
Tropospheric ozone (03) is a pervasive air pollutant that produces pulmonary and cardiovascular dysfunction and there is growing evidence suggesting neurological dysfunction as well. Young and old individuals are generally recognized as being susceptible to ozone toxicity; however, remarkably little is known about susceptibility in old age. Ambient episodic (recurring intermittent) exposures to ozone are common but have rarely been employed in laboratory investigations. This study explored the pulmonary, cardiovascular and neurological effects of episodic ozone exposure in adult and senescent Laboratory rats. An assessment of potential biomarkers of susceptibility was also included. Male Brown Norway rats, 4 (adult) or 20 months (senescent) old (n = 11-12/group) were exposed to filtered air or 0.8 ppm 03 for 6 hours, 1 day per week, for 17 weeks. Ventilatory function was assessed 1 and 7 days after exposure using unrestrained whole body plethysmography. Heart rate and blood pressure (tail cuff), and motor activity, were measured biweekly. Blood and bronchoalveolar lavage were collected 24 hr after the last (1 71h) exposure and analyzed for pulmonary inflammation, hematological endpoints and serum biomarkers. Markers of vascular disease in aorta were also examined at the mRNA level. Age-related differences in air-controls were obtained with many endpoints. Several ozone effects on ventilatory function were obtained, with generally no difference due to age. Measures of normal ventilatory function declined following ozone in both adult and senescent rats, however, senescent rats took longer to exhibit a decline. Some evidence was found for residual respiratory effects of ozone seven days after episodic exposure in both ages of rat. Ozone had no effect on either heart rate or blood pressure, but decreased motor activity in both age groups. Histopathology showed mild, focal terminal bronchiolar thickening. Bronchoalveolar lavage fluid indicated mild neutrophilic inflammation in adult rats and a small degree of protein leakage. Age affected the expression of 17/58 serum analytes, ozone affected 6/58, while just 2/58 showed an age-ozone interaction. Leptin, adiponectin and lipocalin all were increased in senescent rats; ozone further increased lipocalin and insulin in senescent rats. Overall, adult rats exhibited more immediate effects of episodic ozone than senescent rats. Residual effects were, however, obtained in both ages of rat, especially for ventilatory endpoints.
Record Details:Record Type: DOCUMENT (JOURNAL/PEER REVIEWED JOURNAL)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY
TOXICOLOGY ASSESSMENT DIVISION