Adaptive responses induced by low-dose stressors can enhance cellular resilience and system functionality. In this context, ozone, a potent oxidant known for its UV-shielding and antimicrobial properties, has attracted interest over the past decades for its potential therapeutic applications, when administered as a controlled mixture of 1–5% ozone and 95–99% oxygen. Emerging evidence supports the action of this mixture in stimulating the endogenous stress response through induction of moderate oxidative stress, ultimately yielding beneficial effects. The exposure to the mixture contributes to cell homeostasis restoration by activating key biochemical pathways involved in antioxidant defence, and in regulation of inflammation and immune responses, depending on the physiological/pathological condition and the specific cellular context. This review discusses oxygen–ozone mixture molecular mechanisms and its pivotal cellular targets, focusing on cell types for which robust evidence is available from preclinical studies. Comparative analyses of in vitro and in vivo literature data revealed that the oxygen–ozone mixture activates common molecular pathways across different cell types; however, downstream cellular responses diverge substantially, manifesting as adaptive, protective, or regenerative effects and underscoring the need for context-specific therapeutic applications. The ozone influence on stem cell proliferation and differentiation, as well as its potential use as an adjuvant in regenerative medicine, is also addressed. The impact of oxygen-ozone mixture on cellular functions This review examines the molecular mechanisms underlying the action of a controlledmixture of 1–5% ozone and 95–99% oxygen, focusing on cell types for which robust preclinical evidence is available. Exposure to this mixturepromotes the restoration of cellular homeostasis through the activation of key biochemical pathways involved in redox regulation. Comparativeanalyses of in vitro and in vivo data show that, although different cell types exhibit distinct downstream responses that range from adaptive toprotective or regenerative effects, these responses are functionally aligned, as they all contribute to strengthening the cellular antioxidantcapacity. This convergence highlights the central role of redox balance while the distinct responses support the need for context-specifictherapeutic applications
Khalid et al. (Wed,) studied this question.