Experimental evidence for the beneficial effects of low-concentration ozone
Flavia Carton, Carlo Pellicciari, Gabriele Tabaracci, Manuela MalatestaOzone (O 3 ), a molecule consisting of three oxygen atoms, is an unstable compound whose clinical application as a complementary therapy continues to expand. Although numerous clinical studies support its therapeutic potential, the molecular basis of its effects has remained poorly understood. This review summarizes the current knowledge on the cellular and molecular mechanisms activated by low-concentration O 3 . Central to its action is the induction of mild oxidative stress by low concentrations of O 3 , which triggers an antioxidant response mediated through nuclear factor erythroid 2-related factor 2, enhancing cell survival. Additionally, low-concentration O 3 exhibits antiinflammatory properties by modulating cytokine expression, inhibiting metalloproteinases, and activating macrophages. The regenerative potential of low-concentration O 3 may be attributed to the stimulation of fibroblasts, chondrocytes, and osteoblasts. Moreover, the antitumor effects of low-concentration O 3 in cancer cell lines and animal models appear to be linked to the inhibition of cell proliferation and migration, as well as proapoptotic activity. More research is needed to determine the best treatment methods, long-term effectiveness, and standardized clinical procedures for ozone therapy in specific diseases. This review provides a detailed reference for understanding how O 3 therapy works.