9277614_sThe therapeutic efficacy of ozone therapy may be partly due the controlled and moderate oxidative stress produced by the reactions of ozone with several biological components. The line between effectiveness and toxicity of ozone may be dependent on the strength of the oxidative stress. As with exercise, it is well known that moderate exercise is good for health, whereas excessive exercise is not.

Unlike other complementary approaches, all biochemical, physiological and pharmacological mechanisms elicited by ozone are in the realm of orthodox medicine. There is already good evidence that ozone therapy is more useful in chronic limb ischemia than the golden standard (prostacyclin analogues) and patients with skin lesions are very grateful for being able to use ozonated oil. A scheme of bland ozone therapy associated to a correct life-style has been proposed for delaying aging.

Severe oxidative stress activates nuclear transcriptional factor kappa B (NFκB), resulting in an inflammatory response and tissue injury via the production of COX2, PGE2, and cytokines. However, moderate oxidative stress activates another nuclear transcriptional factor, nuclear factor-erythroid 2-related factor 2 (Nrf2). Nrf2 then induces the transcription of antioxidant response elements (ARE). Transcription of ARE results in the production of numerous antioxidant enzymes, such as SOD, GPx, glutathione-s-transferase(GSTr), catalase (CAT), heme-oxygenase-1 (HO-1), NADPH-quinone-oxidoreductase (NQO-1), phase II enzymes of drug metabolism and heat shock proteins (HSP). Both free antioxidants and anti-oxidative enzymes not only protect cells from oxidation and inflammation but they may be able to reverse the chronic oxidative stress. Based on these observations, ozone therapy may also activate Nrf2 via moderate oxidative stress, and suppress NFκB and inflammatory responses. Furthermore, activation of Nrf2 results in protection against neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases. Mild immune responses are induced via other nuclear transcriptional factors, such as nuclear factor of activated T-cells (NFAT) and activated protein-1 (AP-1).

The potential mechanisms of action of ozone therapy are reviewed in this paper.

Sagai, M., & Bocci, V. (2011). Mechanisms of Action Involved in Ozone Therapy: Is healing induced via a mild oxidative stress? Medical Gas Research, 1, 29. http://doi.org/10.1186/2045-9912-1-29