In vivo ozone exposure induces antioxidant/stress-related responses in murine lung and skin

Giuseppe Valacchi, Elisa Pagnin, Ana M. Corbacho, Estibaliz Olano, Paul A. Davis, Lester Packer, Carroll E Cross

Research output: Contribution to journalArticlepeer-review

98 Scopus citations


Lung and skin are the organs directly exposed to environmental pollution. Ozone (O3) is a toxic, oxidant air pollutant, and exposure has been shown to induce antioxidant depletion as well as oxidation of lipids and proteins within the outermost skin layer (stratum corneum) and the lung respiratory tract lining fluids (RTLFs). To further define skin and lung responses to O3 exposure, SKH-1 hairless mice were exposed to either 0.8 ppm of O3 (a level occasionally reached in very polluted areas) or ambient air 6 h/day for 6 consecutive days. O3 exposure resulted in the depletion of α-tocopherol in lung and plasma and induction in both skin and lung of heme oxygenase 1, cyclooxygenase 2, and proliferating cell nuclear antigen. O3-exposed animals showed a similar extent of upregulation of COX-2 and PCNA in lung and skin, whereas HO-1 was more responsive in skin than in lung (7-fold induction vs. 2-fold induction). In addition to these measures of response to oxidative stress, O3 exposure led to the activation of nuclear factor κB measured as IκBα phosphorylation in both tissues. We conclude that in this model, O3 at high pollutant levels is able to affect both lung and skin biology, inducing depletion of α-tocopherol and inducing stress-related responses in both skin epidermis and respiratory tract epithelium.

Original languageEnglish (US)
Pages (from-to)673-681
Number of pages9
JournalFree Radical Biology and Medicine
Issue number5
StatePublished - Mar 1 2004


  • Cyclooxygenase 2
  • Free radicals
  • Heat stress proteins
  • Heme oxygenase
  • Keratinocytes
  • Lipid peroxidation
  • Nuclear factor κB
  • Ozone
  • Proliferating cell nuclear antigen

ASJC Scopus subject areas

  • Medicine(all)
  • Toxicology
  • Clinical Biochemistry


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