Skip to main content
U.S. flag

An official website of the United States government

Here’s how you know

Dot gov

Official websites use .gov
A .gov website belongs to an official government organization in the United States.

HTTPS

Secure .gov websites use HTTPS
A lock ( Lock A locked padlock ) or https:// means you’ve safely connected to the .gov website. Share sensitive information only on official, secure websites.

  • Environmental Topics
  • Laws & Regulations
  • Report a Violation
  • About EPA
Risk Assessment
Contact Us

Neuroendocrine aspect of ozone adaptation at lung and systemic level: The influence of one-month glucocorticoid pretreatment

On this page:

  • Overview
Ozone-induced lung injury and inflammation dissipate despite continuation of exposure for 3 or more days; however, the mechanisms of adaptation/habituation remain unclear. We have shown that ozone-induced pulmonary and systemic effects are mediated through reversible neuroendocrine activation and adrenal release of the stress hormones corticosterone and epinephrine. Here, we hypothesized that adaptation from ozone-induced pulmonary and systemic effects is associated with diminution of neuroendocrine activation and reduced glucocorticoid activity. Male Wistar Kyoto rats (12-week old) were injected daily with vehicle (VEH, saline) or a therapeutically relevant dose of dexamethasone sulfate (DEX, 0.01 mg/kg/day; i.p.) for 1-month to induce glucocorticoid resistance and to determine if reduced glucocorticoid effectiveness is associated with diminution of ozone adaptation response. Saline or DEX-treated rats were exposed to air or 0.8 ppm ozone, 4 hours/day for 2 or 4 days (D+2 or D+4) to assess impacts of acute exposure and characterize adaptation responses, respectively. Acute ozone exposure (D+2) increased lung lavage fluid protein and neutrophils, and decreased circulating lymphocytes; effects that were not evident in D+4. Likewise, ozone-induced hyperglycemia, glucose intolerance and inhibition of beta-cell insulin release in D+2 were attenuated in D+4. This adaptation was modestly attenuated in DEX pretreated rats. Ozone-induced depletion of circulating prolactin, thyroid stimulating hormone, and luteinizing hormone after 2-day exposure were not observed at D+4 suggesting central mediation of adaptation. Genes involved in epinephrine synthesis were similarly induced in adrenals after ozone exposure at D+2 and D+4, however, those involved in glucocorticoid biosynthesis were induced only after D+2 but not D+4 exposure, suggesting involvement of reduced glucocorticoid synthesis in mediating ozone adaptation. These results suggest that ozone adaptation likely involves the lack of hypothalamic-pituitary-adrenal axis activation and glucocorticoid production. (Does not reflect US EPA policy)

Impact/Purpose

The mechanisms of adaptation that occur in animal models and humans after exposure to irritant pollutants are not understood. Based on our findings that neuroendocrine system is involved in mediating ozone health effects, here we assessed its role in animal adaptation to ozone-induced injury and inflammation. We show that glucocorticoid availability and likely the lack of resultant central neuroendocrine activation after repeated ozone exposure are involved in mediating tolerance/adaptation. This is important when understanding how organisms adapt to environmental stressors and what conditions may fail them.

Citation

Kodavanti, U., S. Snow, Mette C. Schladweiler, C. Miller, AND A. Henriquez. Neuroendocrine aspect of ozone adaptation at lung and systemic level: The influence of one-month glucocorticoid pretreatment. Society of Toxicology (SOT) - Virtual, NA, Virtual, March 14 - 18, 2021.
  • Risk Assessment Home
  • About Risk Assessment
  • Risk Recent Additions
  • Human Health Risk Assessment
  • Ecological Risk Assessment
  • Risk Advanced Search
    • Risk Publications
  • Risk Assessment Guidance
  • Risk Tools and Databases
  • Superfund Risk Assessment
  • Where you live
Contact Us to ask a question, provide feedback, or report a problem.
Last updated on April 13, 2021
United States Environmental Protection Agency

Discover.

  • Accessibility Statement
  • Budget & Performance
  • Contracting
  • EPA www Web Snapshots
  • Grants
  • No FEAR Act Data
  • Privacy
  • Privacy and Security Notice

Connect.

  • Data
  • Inspector General
  • Jobs
  • Newsroom
  • Open Government
  • Regulations.gov
  • Subscribe
  • USA.gov
  • White House

Ask.

  • Contact EPA
  • EPA Disclaimers
  • Hotlines
  • FOIA Requests
  • Frequent Questions

Follow.