PMID- 26732886
OWN - NLM
STAT- MEDLINE
DCOM- 20161227
LR  - 20181113
IS  - 1096-0929 (Electronic)
IS  - 1096-6080 (Print)
IS  - 1096-0929 (Linking)
VI  - 150
IP  - 2
DP  - 2016 Apr
TI  - Acute Ozone-Induced Pulmonary and Systemic Metabolic Effects Are Diminished in 
      Adrenalectomized Rats.
PG  - 312-22
LID - 10.1093/toxsci/kfv331 [doi]
AB  - 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.
CI  - Published by Oxford University Press on behalf of the Society of Toxicology 2016. 
      This work is written by US Government employees and is in the public domain in 
      the US.
FAU - Miller, Desinia B
AU  - Miller DB
AD  - *Curriculum in Toxicology, University of North Carolina-Chapel Hill, Chapel Hill, 
      North Carolina 27599; and.
FAU - Snow, Samantha J
AU  - Snow SJ
AD  - Environmental Public Health Division, National Health and Environmental Effects 
      Research Laboratory, U.S. Environmental Protection Agency, Research Triangle 
      Park, North Carolina 27711.
FAU - Schladweiler, Mette C
AU  - Schladweiler MC
AD  - Environmental Public Health Division, National Health and Environmental Effects 
      Research Laboratory, U.S. Environmental Protection Agency, Research Triangle 
      Park, North Carolina 27711.
FAU - Richards, Judy E
AU  - Richards JE
AD  - Environmental Public Health Division, National Health and Environmental Effects 
      Research Laboratory, U.S. Environmental Protection Agency, Research Triangle 
      Park, North Carolina 27711.
FAU - Ghio, Andrew J
AU  - Ghio AJ
AD  - Environmental Public Health Division, National Health and Environmental Effects 
      Research Laboratory, U.S. Environmental Protection Agency, Research Triangle 
      Park, North Carolina 27711.
FAU - Ledbetter, Allen D
AU  - Ledbetter AD
AD  - Environmental Public Health Division, National Health and Environmental Effects 
      Research Laboratory, U.S. Environmental Protection Agency, Research Triangle 
      Park, North Carolina 27711.
FAU - Kodavanti, Urmila P
AU  - Kodavanti UP
AD  - 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.
LA  - eng
GR  - T32 ES007126/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20160105
PL  - United States
TA  - Toxicol Sci
JT  - Toxicological sciences : an official journal of the Society of Toxicology
JID - 9805461
RN  - 66H7ZZK23N (Ozone)
RN  - W980KJ009P (Corticosterone)
RN  - YKH834O4BH (Epinephrine)
SB  - IM
MH  - Acute Lung Injury/blood/chemically induced/*metabolism
MH  - Adrenal Glands/*metabolism/surgery
MH  - Adrenalectomy
MH  - Animals
MH  - Corticosterone/blood
MH  - Epinephrine/blood
MH  - Glucose Intolerance/drug therapy
MH  - Hyperglycemia/blood/chemically induced/*metabolism
MH  - Inhalation Exposure
MH  - Male
MH  - Ozone/*toxicity
MH  - Rats, Inbred WKY
PMC - PMC4881831
OTO - NOTNLM
OT  - HPA-axis
OT  - adrenalectomy
OT  - lung injury
OT  - ozone
OT  - stress response
EDAT- 2016/01/07 06:00
MHDA- 2016/12/28 06:00
PMCR- 2017/04/01
CRDT- 2016/01/07 06:00
PHST- 2016/01/07 06:00 [entrez]
PHST- 2016/01/07 06:00 [pubmed]
PHST- 2016/12/28 06:00 [medline]
PHST- 2017/04/01 00:00 [pmc-release]
AID - kfv331 [pii]
AID - 10.1093/toxsci/kfv331 [doi]
PST - ppublish
SO  - Toxicol Sci. 2016 Apr;150(2):312-22. doi: 10.1093/toxsci/kfv331. Epub 2016 Jan 5.