title: Susceptibility of adult and senescent Brown Norway rats to repeated ozone exposure: an assessment of behavior, serum biochemistry and cardiopulmonary function.
abstract: Ozone (O₃) is a pervasive air pollutant that produces pulmonary and cardiovascular dysfunction and possible neurological dysfunction. Young and old individuals are recognized as being susceptible to O₃; however, remarkably little is known about susceptibility with senescence. This study explored the pulmonary, cardiovascular and neurological effects of O₃ exposure in adult (4 m) and senescent (20 m) Brown Norway rats exposed to 0 or 0.8 ppm O₃ for 6 h, 1 d/week, for 17 weeks. Ventilatory function was assessed 1 and 7 d after each exposure (Buxco). Heart rate, blood pressure (tail cuff) and motor activity were measured biweekly. Blood, aorta and bronchoalveolar lavage fluid (BALF) were analyzed 24 h after the last exposure for pulmonary inflammation, serum biomarkers and aorta mRNA markers of vascular disease. Measures of normal ventilatory function declined following each O₃ exposure in both adult and senescent rats, however, senescent rats took weeks to exhibit a decline. Evidence for residual respiratory effects of O₃ 7 d after exposure in both age groups was observed. O₃ had no effect on either heart rate or blood pressure, but decreased motor activity in both age groups. BALF indicated mild neutrophilic inflammation and protein leakage in adults. Age affected 17/58 serum analytes, O₃ affected 6/58; 2/58 showed an age-O₃ interaction. Leptin, adiponectin, lipocalin and insulin were increased in senescent rats. Overall, adult rats exhibited more immediate effects of episodic O₃ than senescent rats. Residual effects were, however, obtained in both ages of rat, especially for ventilatory endpoints.
authors: Toxicity Assessment Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA. gordon.christopher@epa.gov
authors: C J
authors: CJ
authors: Gordon
authors: K A
authors: KA
authors: Jarema
authors: J R
authors: JR
authors: Lehmann
authors: A D
authors: AD
authors: Ledbetter
authors: M C
authors: MC
authors: Schladweiler
authors: J E
authors: JE
authors: Schmid
authors: W O
authors: WO
authors: Ward
authors: U P
authors: UP
authors: Kodavanti
authors: A
authors: A
authors: Nyska
authors: R C
authors: RC
authors: MacPhail
mesh_terms: D052242:Adiponectin / Q000378:metabolism; D000367:Age Factors; D000375:Aging; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D015415:Biomarkers / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D004198:Disease Susceptibility; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D007328:Insulin / Q000378:metabolism; D020738:Leptin / Q000378:metabolism; D054834:Lipocalins / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010083:Oxidants, Photochemical / Q000633:toxicity*; D010126:Ozone / Q000633:toxicity*; D051381:Rats; D011914:Rats, Inbred BN; D012129:Respiratory Function Tests
chemical_list: D052242:Adiponectin; D015415:Biomarkers; D007328:Insulin; D020738:Leptin; D054834:Lipocalins; D010083:Oxidants, Photochemical; D010126:Ozone