Citation:

Snow, S., A. Henriquez, M. Schladweiler, M. Hargrove, C. Miller, W. Williams, AND U. Kodavanti. Dynamic Changes in Neuroendocrine Hormones and Inflammatory Cell Egress Following an Acute Ozone Exposure in Rats. Society of Toxicology Annual Meeting, Baltimore, Maryland, March 10 - 14, 2019.

Impact/Purpose:

Acute exposure to ozone leads to multi-organ alterations through activation of the sympathetic-adrenal-medullary and hypothalamic-pituitary-adrenal axis, which control the synthesis and release from adrenal glands of epinephrine and glucocorticoids, respectively. These hormones regulate and maintain homeostasis through modulating changes in two fundamental survival processes in the body: metabolism and immune response. The purpose of this study was to elucidate the temporal sequence behind ozone-induced metabolic alterations and innate immune response to the lung by constructing a time line of events for stress hormone release and egress of immune cells. These temporal datasets are critical for the accurate characterization of injury mechanisms as well as the development of predictive, computational models of the adverse effects of environmental stressors.

Description:

Acute exposure to ozone leads to multi-organ alterations through activation of the sympathetic-adrenal-medullary and hypothalamic-pituitary-adrenal axis, which control the synthesis and release from adrenal glands of epinephrine and glucocorticoids, respectively. These hormones regulate and maintain homeostasis through modulating changes in two fundamental survival processes in the body: metabolism and immune response. The purpose of this study was to elucidate the temporal sequence behind ozone-induced metabolic alterations and innate immune response to the lung by constructing a time line of events for stress hormone release and egress of immune cells. Male, 12-14 weeks old Wistar-Kyoto rats were exposed to filtered air or ozone (0.4 or 0.8 ppm) for 30 min, 1h, 2h, or 4h followed immediately by necropsy to collect blood and tissues for analysis. Circulating hormones were measured in plasma or serum samples. The levels of thyroid stimulating hormone, luteinizing hormone, and prolactin steadily decreased with increased exposure times to 0.8 ppm ozone. Adrenocorticotrophin, which stimulates the release of corticosterone from the adrenal cortex, was increased at 30 min (p=0.0759), 1h, and 2h. This was prior to the elevation of corticosterone at 1h, 2h, and 4h post-exposure to 0.8 ppm ozone. Ozone exposure (0.8 ppm) led to significant increases in epinephrine levels at the 1h, 2h, and 4h timepoints, illustrating the rapid response of these stress response pathways. These findings corresponded with significant increases in free fatty acids (1h, 2h, and 4h), total cholesterol (4h), and blood glucose levels (4h) following exposure to the high dose of ozone. Furthermore, ozone exposure at 0.8 ppm led to significant decreases in circulating white blood cells and lymphocytes at the 4h timepoint. Neither apoptotic nor necrotic white blood cell subpopulations were altered, suggesting mobilization into tissues rather than cell death was responsible for the decreased count. Collectively, these findings help elucidate the temporal mechanisms that lead to the release of neuroendocrine hormones, metabolic alterations, and immune responses following ozone exposure. These temporal datasets are critical for the accurate characterization of injury mechanisms as well as the development of predictive, computational models of the adverse effects of environmental stressors.

Record Details: