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Evid Based Complement Alternat Med. 2019 Nov 18;2019:2169103. doi: 10.1155/2019/2169103. eCollection 2019.

Ozone Exerts Cytoprotective and Anti-Inflammatory Effects in Cardiomyocytes and Skin Fibroblasts after Incubation with Doxorubicin.

Author information

"Kaos" ONLUS Foundation, Turin, Italy.
Oxygen-Ozone Therapy Scientific Society (SIOOT), Gorle, Italy.
Division of Cardiology, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, Napoli, Italy.
University of Pavia, Pavia, Italy.
ASMO (Association of Multidisciplinary Study in Oncology) and Mediterranean Diet, Piazza Nicola Amore, Napoli, Italy.



Skin reactions and cardiotoxicity are one of the most common side effects of doxorubicin in cancer patients. The main mechanisms based on the etiopathogenesis of these reactions are mediated by the overproduction of proinflammatory cytokines, metalloproteases, and the disruption of mitochondrial homeostasis. Ozone therapy demonstrated anti-inflammatory effects in several preclinical and clinical studies. The aim of this research is based on the evaluation of cardioprotective and dermatoprotective effects of ozone during incubation with doxorubicin, giving preliminary evidences for further studies in the field of cardio-oncology.


Human skin fibroblast cells and human fetal cardiomyocytes were exposed to doxorubicin at subclinical concentration (100 nM) alone or combined with ozone concentrated from 10 up to 50 μg/mL. Cell viability and multiple anti-inflammatory studies were performed in both cell lines, with particular attention on the quantification of interleukins, leukotriene B4, NF-κB, and Nrf2 expressions during treatments.


Ozone decreased significantly the cytotoxicity of doxorubicin in skin fibroblasts and cardiomyocytes after 24 h of incubation. The best cytoprotective effect of ozone was reached to 30 μg/mL with a plateau phase at higher concentration. Ozone also demonstrated anti-inflammatory effects decreasing significantly the interleukins and proinflammatory mediators in both cells.


Ozone exerts cardioprotective and dermatoprotective effects during incubation with doxorubicin, and the involved mechanisms are mediated by its anti-inflammatory effects. The overall picture described herein is a pilot study for preclinical studies in oncology.

Conflict of interest statement

The authors also declare that Dr. Simonetti is the past President of the KAOS ONLUS Association and a board member of SIOOT, and Dr. Valdenassi is the President of SIOOT.

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