Ozone Therapy as a Controlled Modulator of Redox Signaling and Adaptive Stress Responses: Molecular Mechanisms, Hormetic Effects, and Biomedical Implications

Medical ozone has emerged as a potential redox-modulating intervention in inflammatory and degenerative conditions, particularly in dermatological contexts characterized by chronic oxidative imbalance and impaired tissue remodeling. Unlike conventional pharmacological agents, ozone exerts its biological activity through rapid chemical reactions generating transient reactive and electrophilic species that activate endogenous adaptive signaling pathways. Controlled oxidative perturbations activate antioxidant transcriptional programs, primarily mediated by the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, while modulating inflammatory signaling networks, including nuclear factor kappa B (NF-κB) and the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome. This dual behavior reflects hormetic responses in which low-dose exposure promotes adaptive cellular signaling, whereas excessive oxidative burden leads to structural and functional damage. This review summarizes current knowledge on the molecular mechanisms underlying ozone-induced redox modulation, with emphasis on chemical reactivity, spatiotemporal signaling dynamics, thiol-based sensing, and metabolic reinforcement of antioxidant defenses. Particular attention is given to skin and subcutaneous adipose tissue, where oxidative stress, immune activation, and extracellular matrix remodeling converge. Dose dependency, safety constraints, and methodological variability are critically discussed, highlighting the narrow threshold between adaptive signaling and oxidative injury and the need for rigorous mechanistic and clinical validation.