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Ozone Induced Impairment of Systemic Metabolic Processes: Influence of Prior Ozone Exposure and Metformin Pre-treatment on Aged Wistar Kyoto (WKY) Rats.
Citation:
Bass, V., D. Andrews, J. Richards, M. Schladweiler, A. Ledbetter, D. Miller, AND U. Kodavanti. Ozone Induced Impairment of Systemic Metabolic Processes: Influence of Prior Ozone Exposure and Metformin Pre-treatment on Aged Wistar Kyoto (WKY) Rats. Presented at Society of Toxicology, Phoenix, AZ, March 23 - 27, 2014.
Impact/Purpose:
This study shows that prior ozone exposure does not impact subsequent ozone induced metabolic impairment and that ozone induced metabolic health effects are not reduced by pretreating rats with anti-diabetogenic drug metformin that increases tissue glucose uptake suggesting that ozone likely does not impair glucose uptake by muscle or adipose tissues.
Description:
SOT2014 Abstract for presentation: March 23-27, 2014; Phoenix, AZ Ozone Induced Impairment of Systemic Metabolic Processes: Influence of Prior Ozone Exposure and Metformin Pre-treatment on Aged Wistar Kyoto (WKY) Rats. V. Bass, D. Andrews, J. Richards, M. Schladweiler, A. Ledbetter, D. Miller, U. Kodavanti. NHEERL, USEPA, Research Triangle Park, NC Ozone exposure (O3) is associated with adverse cardiopulmonary health effects in humans and thought to produce metabolic impairment, such as insulin resistance. Recently, we showed that acute O3 exposure caused glucose intolerance and increased serum leptin and epinephrine in aged Brown Norway rats. We hypothesized that 1) subchronic pre-exposure to O3 at a young age would predispose rats to exacerbated metabolic effects of subsequent O3 exposure later in life and 2) metabolic effects of O3 would be diminished in aged rats pretreated with metformin to improve tissue glucose uptake. WKY rats were exposed to O3 at 0 or 0.5 ppm 6h/dx2days/week x 13 weeks starting at 3 months of age. To study the effects of pre-exposure, the same rats were re-exposed to 0 or 1ppm ozone acutely for 6h at 14 months of age. To examine if treatment to improve glucose uptake would reduce the effects ozone, another group of 18 month old WKY rats were treated with the anti-diabetic drug metformin in drinking water (3g/L) for 2 weeks prior to a 6h/day x 2 day acute exposure to 0 or 1ppm ozone. Glucose tolerance tests (GTT), serum, and Broncheoaveolar lavage fluid (BALF) analyses were done immediately after exposure in both studies. Marked age-related impairment of glucose tolerance was observed. Additionally, O3 exposure caused further impairment of glucose tolerance. O3 exposure resulted in acute lung injury/inflammation and increases in serum levels of leptin, insulin, cholesterol and triglycerides in aged WKY rats. Pre-exposure to ozone had no significant impact on any of these parameters. Treatment with metformin did not reduce ozone-induced lung injury or glucose intolerance, but decreased serum leptin and insulin in all rats. Our results suggest that pre-exposure to O3 does not impact response to re-exposure at an older age. We believe that the metabolic effects of ozone are not mediated by impaired cellular glucose regulation. (Does not reflect US EPA policy).