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Eur J Pharmacol. 2017 Sep 15;811:148-154. doi: 10.1016/j.ejphar.2017.06.017. Epub 2017 Jun 13.

Medical ozone promotes Nrf2 phosphorylation reducing oxidative stress and pro-inflammatory cytokines in multiple sclerosis patients.

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Department of Pharmacology, Institute of Marine Sciences, Havana 10600, Cuba. Electronic address:
Department of Pharmacology, Institute of Marine Sciences, Havana 10600, Cuba.
Instituto de Ciencias Biomédicas, Universidad Autónoma de Ciudad Juárez, Ciudad Juárez 32315, Chihuahua, Mexico.
Pharmacy and Food Science Institute, University of Havana, Havana, Cuba.
Laboratory of Oxidative Stress, Mexican Association of Oxidative Stress, Mexico D.F., Mexico.
Medical Center Beauty Benefit - San Biagio di Osimo, Via Mons. Oscar Romero, 31, 60027 Osimo, Ancona, Italy.
Department of Pharmacology, Medicine College, Mutah University, Jordan.


Oxidative stress and inflammation play key roles in the pathogenesis of Multiple sclerosis (MS). Different drugs have been used in the clinical practice, however, there is not a completely effective treatment. Due to its potential therapeutic action, medical ozone represents a promising approach for neurodegenerative disorders. The aim of the present study was to address the role of ozone therapy on the cellular redox state in MS patients. Ozone (20μg/ml) was administered three times per week during a month by rectal insufflation. The effect of ozone therapy on biomarkers of oxidative stress and inflammation was addressed by spectrophotometric and immunoenzymatic assays. Furthermore, we investigated the action of ozone on CK2 expression and Nrf2 phosphorylation by western blotting analysis. Medical ozone significantly improved (P < 0.05) the activity of antioxidant enzymes and increased the levels of cellular reduced glutathione. In accordance, a significant reduction (P < 0.05) of oxidative damage on lipids and proteins was observed in ozone-treated patients. As well, the levels of pro-inflammatory cytokines TNFα and IL-1β were lower after ozone treatment. Ozone therapy incremented the CK2 expression together with Nrf2 phosphorylation in mononuclear cells of MS patients. These findings suggest that ozone´s antioxidant and anti-inflammatory effects might be partially associated with an induction of Nrf2 phosphorylation and activation. These results provide new insights on the molecular events modulated by ozone, and pointed out ozone therapy as a potential therapeutic alternative for MS patients.


CK2 expression; Multiple sclerosis; Nrf2 phosphorylation; Oxidative stress; Ozone therapy; Pro-inflammatory cytokines

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