Susceptibility of adult and senescent Brown Norway rats to repeated ozone exposure: an assessment of behavior, serum biochemistry and cardiopulmonary function

Self Cite

Setting exposure standards for environmental pollutants may consider the aged as a susceptible population but the few published studies assessing susceptibility of the aged to air pollutants are inconsistent. Episodic ozone (O₃) is more reflective of potential exposures occurring in human populations and could be more harmful to the aged. This study used radiotelemetry to monitor heart rate (HR), core temperature (T(c)) and motor activity (MA) in adult (9-12 months) and senescent (20-24 months) male, Brown Norway rats exposed to episodic O₃ (6 h/day of 1 ppm O₃ for 2 consecutive days/week for 13 weeks). Acute O₃ initially led to marked drops in HR and T(c). As exposures progressed each week, there was diminution in the hypothermic and bradycardic effects of O₃. Senescent rats were less affected than adults. Acute responses were exacerbated on the second day of O₃ exposure with adults exhibiting greater sensitivity. During recovery following 2 d of O₃, adult and senescent rats exhibited an elevated T(c) and HR during the day but not at night, an effect that persisted for at least 48 h after O₃ exposure. MA was elevated in adults but not senescent rats during recovery from O₃. Overall, acute effects of O₃, including reductions in HR and T(c), were attenuated in senescent rats. Autonomic responses during recovery, included an elevation in T(c) with a pattern akin to that of a fever and rise in HR that were independent of age. An attenuated inflammatory response to O₃ in senescent rats may explain the relatively heightened physiological response to O₃ in younger rats.

Section: Discussionmentioning

confidence: 99%

Episodic ozone exposure in adult and senescent Brown Norway rats: acute and delayed effect on heart rate, core temperature and motor activity

Gordon

Johnstone

Aydin

et al. 2014

Self Cite

“…Aliquots of BALF were used to determine total cell counts with a Z1 Coulter Counter (Coulter, Inc., Miami, FL) and cell differentials according to previously described procedures (Gordon et al, 2013). The cell free BALF was used to analyze lung injury biomarkers [total protein, albumin lactate dehydrogenase (LDH) activity, N-acetyl glucosaminidase (NAG) activity and γ-glutamyl transferase (GGT)] activity as described earlier (Gordon et al, 2013).…”

Section: Methodsmentioning

confidence: 99%

Comparative cardiopulmonary toxicity of exhausts from soy-based biofuels and diesel in healthy and hypertensive rats

Bass

Schladweiler

Nyska

et al. 2015

Increased use of renewable energy sources raise concerns about health effects of new emissions. We analyzed relative cardiopulmonary health effects of exhausts from (1) 100% soy biofuel (B100), (2) 20% soy biofuel + 80% low sulfur petroleum diesel (B20), and (3) 100% petroleum diesel (B0) in rats. Normotensive Wistar–Kyoto (WKY) and spontaneously hypertensive rats were exposed to these three exhausts at 0, 50, 150 and 500 μg/m3, 4 h/day for 2 days or 4 weeks (5 days/week). In addition, WKY rats were exposed for 1 day and responses were analyzed 0 h, 1 day or 4 days later for time-course assessment. Hematological parameters, in vitro platelet aggregation, bronchoalveolar lavage fluid (BALF) markers of pulmonary injury and inflammation, ex vivo aortic ring constriction, heart and aorta mRNA markers of vasoconstriction, thrombosis and atherogenesis were analyzed. The presence of pigmented macrophages in the lung alveoli was clearly evident with all three exhausts without apparent pathology. Overall, exposure to all three exhausts produced only modest effects in most endpoints analyzed in both strains. BALF γ-glutamyl transferase (GGT) activity was the most consistent marker and was increased in both strains, primarily with B0 (B0>B100>B20). This increase was associated with only modest increases in BALF neutrophils. Small and very acute increases occurred in aorta mRNA markers of vasoconstriction and thrombosis with B100 but not B0 in WKY rats. Our comparative evaluations show modest cardiovascular and pulmonary effects at low concentrations of all exhausts: B0 causing more pulmonary injury and B100 more acute vascular effects. BALF GGT activity could serve as a sensitive biomarker of inhaled pollutants.

“…A proprietary algorithm within the software automatically pre-screens measurements for acceptability, and rejects values falling outside of a pre-programmed range. Components of the plethysmography system and its operation are described elsewhere (Gordon et al, 2013;Hamelmann et al, 1997;Shannahan et al, 2010) and are unchanged from previous studies, with the exception of the N-O plethysmographs, which we had not previously utilized. The N-O plethysmographs were used following the manufacturer's instructions, with the exception that the pneumotachometers, which convert air flow in the plethysmograph into quantifiable signals representing changes in air pressure, were moved from the cone's rear sidewall to the back of the rear plunger (similar to N-O plethysmographs for mice), to prevent interference with the screen by fur or dander.…”

Section: Plethysmograph Exposure System (Experiments 2)mentioning

confidence: 98%

Use of novel inhalation kinetic studies to refine physiologically-based pharmacokinetic models for ethanol in non-pregnant and pregnant rats

Martin¹,

Oshiro²,

Evansky³

et al. 2014

Ethanol (EtOH) exposure induces a variety of concentration-dependent neurological and developmental effects in the rat. Physiologically-based pharmacokinetic (PBPK) models have been used to predict the inhalation exposure concentrations necessary to produce blood EtOH concentrations (BEC) in the range associated with these effects. Previous laboratory reports often lacked sufficient detail to adequately simulate reported exposure scenarios associated with BECs in this range, or lacked data on the time-course of EtOH in target tissues (e.g. brain, liver, eye, fetus). To address these data gaps, inhalation studies were performed at 5000, 10 000, and 21 000 ppm (6 h/d) in non-pregnant female Long-Evans (LE) rats and at 21 000 ppm (6.33 h/d) for 12 d of gestation in pregnant LE rats to evaluate our previously published PBPK models at toxicologically-relevant blood and tissue concentrations. Additionally, nose-only and whole-body plethysmography studies were conducted to refine model descriptions of respiration and uptake within the respiratory tract. The resulting time-course and plethysmography data from these in vivo studies were compared to simulations from our previously published models, after which the models were recalibrated to improve descriptions of tissue dosimetry by accounting for dose-dependencies in pharmacokinetic behavior. Simulations using the recalibrated models reproduced these data from non-pregnant, pregnant, and fetal rats to within a factor of 2 or better across datasets, resulting in a suite of model structures suitable for simulation of a broad range of EtOH exposure scenarios.