The Role of Nrf2 in the Antioxidant Cellular Response to Medical Ozone Exposure

Int J Mol Sci. 2019 Aug 17;20(16):4009. doi: 10.3390/ijms20164009.


Ozone (O3) is a natural, highly unstable atmospheric gas that rapidly decomposes to oxygen. Although not being a radical molecule, O3 is a very strong oxidant and therefore it is potentially toxic for living organisms. However, scientific evidence proved that the effects of O3 exposure are dose-dependent: high dosages stimulate severe oxidative stress resulting in inflammatory response and tissue injury, whereas low O3 concentrations induce a moderate oxidative eustress activating antioxidant pathways. These properties make O3 a powerful medical tool, which can be used as either a disinfectant or an adjuvant agent in the therapy of numerous diseases. In this paper, the cellular mechanisms involved in the antioxidant response to O3 exposure will be reviewed with special reference to the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) and its role in the efficacy of ozone therapy.

Keywords: adipose biology; cancer; inflammation; mitochondria; oxidative stress; ozone therapy; proteostasis.

Publication types

  • Review

MeSH terms

  • Animals
  • Antioxidants / metabolism*
  • Humans
  • Inflammation*
  • NF-E2-Related Factor 2 / metabolism*
  • Neoplasms / drug therapy
  • Neoplasms / metabolism
  • Oxidative Stress*
  • Ozone / pharmacology*
  • Ozone / therapeutic use
  • Treatment Outcome


  • Antioxidants
  • NF-E2-Related Factor 2
  • Ozone