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Acute Ozone-Induced Pulmonary and Systemic Metabolic Effects are Diminished in Adrenalectomized Rats
Citation:
Miller, D., M. Schladweiler, S. Snow, J. Richards, D. Andrews, Andy Ghio, A. Ledbetter, AND U. Kodavanti. Acute Ozone-Induced Pulmonary and Systemic Metabolic Effects are Diminished in Adrenalectomized Rats. Society of Toxicology, New Orleans, LA, March 13 - 17, 2016.
Impact/Purpose:
This study provides mechanistic evidence of involvement of hypothalamus pituitary adrenal stress axis in mediating ozone induced systemic metabolic and pulmonary health effects.
Description:
Acute ozone exposure increases circulating stress hormones and induces peripheral metabolic alterations in animals and humans. We hypothesized that the increase of adrenal-derived stress hormones is necessary for ozone-induced systemic metabolic effects and lung injury. Male Wistar-Kyoto rats (12 week-old) underwent total bilateral adrenalectomy (ADREX), adrenal demedullation (DEMED) or sham surgery (SHEM). After 4 day recovery, rats were exposed to air or ozone (1ppm), 4h/day for 1 or 2 days. Circulating adrenaline levels dropped to nearly zero in DEMED and ADREX rats relative to air-exposed SHAM. Corticosterone levels tended to be low in DEMED rats and dropped to nearly zero in ADREX rats. Adrenalectomy in air-exposed rats caused modest changes in metabolites and lung toxicity parameters. Ozone-induced hyperglycemia and glucose intolerance were markedly attenuated in DEMED with nearly complete reversal in ADREX rats. Ozone increased circulating epinephrine and corticosterone in SHAM but not in DEMED or ADREX rats. Free fatty acids and branched-chain amino acids tended to increase after ozone exposure in SHAM but not in DEMED or ADREX rats. Lung minute volume was not affected by surgery or ozone but ozone-induced labored breathing was less pronounced in ADREX rats. Ozone-induced increases in lung protein leakage and neutrophilic inflammation were markedly reduced in DEMED and ADREX rats (ADREX>DMED). Ozone-mediated decrease in circulating WBC in SHAM was not observed in DEMED and ADREX rats. We show that ozone-induced peripheral metabolic effects and lung injury/inflammation are mediated through adrenal-derived stress hormones as a result of activation of stress response pathway. (Does not reflect EPA Policy).