Citation:

Kodavanti, U., A. Henriquez, M. Schladweiler, C. Miller, C. Fisher, R. Grindstaff, AND S. Snow. Neuroendocrine stress axes and adaptation after repeated daily ozone exposure. Society of Toxicology, Baltimore, MD, March 10 - 14, 2019.

Impact/Purpose:

Adaptation to repeated exposure to stressors and ozone are well documented, however the mechanisms remain unclear. These results demonstrate that adaptation to repeated ozone exposure is noted in not only pulmonary but also neuroendocrine pathways, and that long-term steroid pretreatment had a small effect on the adaptation to lung injury and inflammation.

Description:

After repeated daily ozone exposure for more than 2 days, rodents demonstrate adaptation/acclimatization from initial lung injury, inflammation and functional alterations. The mechanisms of adaptation to ozone, other pollutants, or non-chemical stressors are not well known. We hypothesized that since ozone-induced lung injury and inflammation are mediated through the activation of neuroendocrine pathways, the adaptive response to initial lung injury and inflammation might involve the lack of neuroendocrine response, and that low level 1-month exogenous glucocorticoid treatment might result in steroid resistance and impairment of adaptation. Male Wistar Kyoto rats (12-week old) were treated with saline or dexamethasone sulfate (DEX, 0.01 mg/kg/day; 7 days/week for 4 weeks; ip) prior to and during daily exposure to air or 0.8 ppm ozone, 4h/day, for 2 or 4 days. Lung injury/inflammation and systemic neuroendocrine changes were assessed post-exposure. Body, thymus and spleen weights were lower in animals treated with DEX when compared to saline controls. DEX reduced circulating adrenocorticotropic hormone in all animals, however, it had no effect on prolactin (PRL), luteinizing hormone (LH) or thyroid stimulating hormone (TSH) levels. Ozone exposure for 2, but not 4 days, was associated with a remarkable depletion of PRL, LH and TSH regardless of DEX treatment. DEX-treatment was associated with ~80% depletion of circulating corticosterone in all air-exposed rats. Ozone exposure for 2, but not 4 days, reversed this depletion, suggesting that adaptation was associated with reduced release of glucocorticoids. Ozone-induced hyperglycemia, glucose intolerance and inhibition of insulin release in response to glucose noted after 2 days were not present after 4 days, indicating adaptation of metabolic response. This adaptation was not influenced by DEX. The lung injury/inflammation and increased lavage fluid IL-6 levels noted after the 2nd day of ozone exposure was not observed after the 4th day of exposure in saline-pretreated rats, however, this adaptation was less pronounced in DEX-treated rats. These results demonstrate that adaptation to repeated ozone exposure is noted in not only pulmonary but also neuroendocrine pathways, and that long-term steroid pretreatment had a small effect on the adaptation to lung injury and inflammation. (Does not reflect US EPA policy).

Record Details: