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Bittersweet: Real-Time, Dynamic Changes in Blood Glucose Levels during an Acute Ozone Exposure in Rats
Snow, S., W. Cheng, A. Henriquez, A. Farraj, M. Hazari, R. Conolly, AND U. Kodavanti. Bittersweet: Real-Time, Dynamic Changes in Blood Glucose Levels during an Acute Ozone Exposure in Rats. Society of Toxicology, San Antonio, TX, March 11 - 15, 2018.
This research demonstrates the ability to acquire dynamic temporal data for biomolecules in freely-moving animals prior to, during, and following exposure, which is critical for support of computational modeling of biological effects of environmental stressors.
In humans and rats, acute exposures to ozone have been shown to activate the sympathetic-adrenal-medullary and hypothalamic-pituitary-adrenal axes to induce multi-organ metabolic alterations including impaired glucose homeostasis. These findings have largely been gleaned from one-time snapshots of responses measured after exposure. The complexity of such responses, however, requires a multidimensional view of in-life, dynamic biomolecular changes across time for accurate elucidation of etiology. The purpose of this study was to use new radio-telemetry technology capable of providing real-time quantitative glucose and core body temperature data to assess the impacts of ozone exposure across time and exposure level. We hypothesized that new radio-telemetry technology involving real-time quantitative glucose and core body temperature monitoring will allow live acquisition of changes in circulating biomolecules during an ozone exposure in rats. Male, 13 week old Wistar-Kyoto rats (n=8) were implanted with HD-XG glucose telemeters (DSI, St. Paul, MN) using aseptic techniques. Following a 2-week recovery, animals were exposed to 0.0, 0.2, 0.4, and 0.8 ppm ozone, 4h/day for 1 day/week for 4 consecutive weeks in a crossover design to ensure that all 8 implanted animals were exposed to each concentration. During the 4 weeks of exposure, blood glucose levels, core body temperature, and locomotor activity were continuously monitored prior to, during, and following ozone exposure. Approximately 1.5h into the exposure at 0.8 ppm ozone, blood glucose levels rapidly increased as core body temperature simultaneously decreased. In addition to establishing a concentration response curve, we performed a glucose tolerance test immediately following an acute 4h exposure to 0.0 and 0.8 ppm ozone over a 2-week period using a crossover design. These data revealed the temporal dynamics of ozone-induced hyperglycemia and glucose intolerance. Collectively, these data demonstrate the ability to acquire dynamic temporal data for biomolecules in freely-moving animals prior to, during, and following exposure, which is critical for support of computational modeling of biological effects of environmental stressors. (This abstract does not reflect US EPA Policy)