Is ozone pre-conditioning effect linked to Nrf2/EpRE activation pathway in vivo? A preliminary result

Eur J Pharmacol. 2014 Nov 5;742:158-62. doi: 10.1016/j.ejphar.2014.08.029. Epub 2014 Sep 16.


The present preliminary study has been focused on verifying whether ozone preconditioning may be linked to Nrf2/EpRE (nuclear factor erythroid 2/electrophile-responsive element) activation pathway in vivo. Healthy volunteers received a total of three Major Auto-Hemotherapy (MAH) treatments, with treatments administered every second day. The amount of blood used for each subject was standardized to the value obtained multiplying the subject׳s body weight by 1.3 in order to ensure the same ozone concentrations for each subject. A parallel group (n=50) age and gender matched was used as reference for the experimental variables related to the oxidative stress parameters. Levels of Nrf2 and oxidative stress index were measured throughout the study. Levels of Nrf2 (P<0.01) in peripheral blood mononuclear cells (PBMC) were found to increase immediately after ozone/oxygen exposure (35µg/ml, prior to reinfusion). This effect was still detected (P<0.05) in total circulating PBMC when measured 30min following reinfusion. After a series of 3 MAH, Nrf2 returned back to the basal level. At the end of the experiment the activities of superoxide dismutase and catalase were increased (P<0.05). These data demonstrate for the first time in vivo the activation of the Nrf2 pathway by a low dose of ozone and the promotion of the feedback mechanism that induces the synthesis of proteins which collectively favors cell survival.

Keywords: Autohemotherapy; Electrophile-responsive element; EpRE; Nrf2; Nuclear factor erythroid 2; Ozone therapy.

Publication types

  • Controlled Clinical Trial

MeSH terms

  • Adult
  • Antioxidant Response Elements / drug effects*
  • Female
  • Humans
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / metabolism
  • Male
  • Metabolic Networks and Pathways / drug effects
  • NF-E2-Related Factor 2 / blood*
  • Oxidative Stress / drug effects
  • Ozone / administration & dosage*
  • Ozone / therapeutic use
  • Prospective Studies


  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • Ozone