title: Acute Ozone-Induced Pulmonary and Systemic Metabolic Effects Are Diminished in Adrenalectomized Rats.
abstract: Acute ozone exposure increases circulating stress hormones and induces metabolic alterations in animals. We hypothesized that the increase of adrenal-derived stress hormones is necessary for both ozone-induced metabolic effects and lung injury. Male Wistar-Kyoto rats underwent bilateral adrenal demedullation (DEMED), total bilateral adrenalectomy (ADREX), or sham surgery (SHAM). After a 4 day recovery, rats were exposed to air or ozone (1 ppm), 4 h/day for 1 or 2 days and responses assessed immediately postexposure. Circulating adrenaline levels dropped to nearly zero in DEMED and ADREX rats relative to SHAM. Corticosterone 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 rats 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 (P = .15) and branched-chain amino acids increased 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 > DEMED). Ozone-mediated decreases in circulating white blood cells in SHAM were not observed in DEMED and ADREX rats. We demonstrate that ozone-induced peripheral metabolic effects and lung injury/inflammation are mediated through adrenal-derived stress hormones likely via the activation of stress response pathway.
authors.affiliation: *Curriculum in Toxicology, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina 27599; and.
authors.forename: Desinia B
authors.initials: DB
authors.lastname: Miller
authors.affiliation: Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711.
authors.forename: Samantha J
authors.initials: SJ
authors.lastname: Snow
authors.affiliation: Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711.
authors.forename: Mette C
authors.initials: MC
authors.lastname: Schladweiler
authors.affiliation: Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711.
authors.forename: Judy E
authors.initials: JE
authors.lastname: Richards
authors.affiliation: Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Ghio
authors.affiliation: Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711.
authors.forename: Allen D
authors.initials: AD
authors.lastname: Ledbetter
authors.affiliation: Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711 kodavanti.urmila@epa.gov.
authors.forename: Urmila P
authors.initials: UP
authors.lastname: Kodavanti
mesh_terms: D055371:Acute Lung Injury / Q000097:blood / Q000139:chemically induced / Q000378:metabolism*; D000311:Adrenal Glands / Q000378:metabolism* / Q000601:surgery; D000315:Adrenalectomy; D000818:Animals; D003345:Corticosterone / Q000097:blood; D004837:Epinephrine / Q000097:blood; D018149:Glucose Intolerance / Q000188:drug therapy; D006943:Hyperglycemia / Q000097:blood / Q000139:chemically induced / Q000378:metabolism*; D019570:Inhalation Exposure; D008297:Male; D010126:Ozone / Q000633:toxicity*; D011921:Rats, Inbred WKY
chemical_list: D010126:Ozone; D003345:Corticosterone; D004837:Epinephrine
keywords: HPA-axis; adrenalectomy; lung injury; ozone; stress response