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A. Schwartz

Clínica Fiorela, Madrid, Spain


The Nuclear factor, Nrf2 is a master transcription factor that regulates EpRE or antioxidant response element (ARE) or human antioxidant response element (hARE) in human, mediated expression genes encoding antioxidant enzymes and cytoprotective proteins to cellular stresses. These Nrf2-regulated genes can be classified into phase II xenobiotic-metabolizing enzymes antioxidants, molecular chaperones, DNA repair enzymes, and anti-inflammatory response proteins, thereby reducing reactive compounds such as electrophiles and free radicals to less toxic intermediates whilst increasing the ability of the cell to repair any damage ensued. Importantly, Nrf2 has been shown to possess an EpRE sequence within its own promoter region providing a platform for Nrf2 to initiate its own transcription further enhancing the adaptive cell defense response.

Recent studies suggest that the sequence context of the EpRE (electrophile-responsive element) the nature of the chemical inducers, and the cell type are important for determining the activity of the enhancer in a particular gene. The evidence of the EpRE pathway was observed also for some xenobiotics modulating the regulation of Phase I and Phase II drug-metabolizing enzymes. Nrf2 is a powerful protein located within each cell in the body and it is activated by an Nrf2 activator. Once released it migrates into the cell nucleus and bonds to the DNA at the location of the EpRE which is the master regulator of the entire antioxidant system located in all human cells. We know that excessive free radicals induce better antioxidant production through this pathway, but the question is: ozone also does? It seems that ex vivo it does. However what does occur in vivo in the patient’s blood? It Is ozone able to induce and trigger throughout Nrf2 the production of thousands of antioxidant molecules, providing far better protection against the brain and total body damaging effects from free radicals?


Key words: ozone, ozone therapy, Nrf2, nuclear factor erythroid 2, Autohemotherapy, EpRE, electrophile-responsive element