Induction of protective proteins is fundamental to hyperbaric oxygen preconditioning.

Hyperbaric oxygen (HBO) therapy involves the administration of 100% oxygen at elevated atmospheric pressure and has long been utilized for both therapeutic and prophylactic purposes. While early applications of HBO pretreatment primarily emphasized denitrogenation and denucleation to prevent decompression sickness in diving and aerospace settings, accumulating preclinical studies and clinical evidence now indicate that HBO pretreatment's broader protective effects are mediated by preconditioning. Central to this process is the generation of reactive oxygen species (ROS), which serve as critical signaling molecules that trigger adaptive cellular responses upon exposure to HBO. ROS induced by HBO activates key transcriptional regulators, including nuclear factor erythroid 2-related factor 2, heat shock factor 1, and hypoxia-inducible factor-1α, leading to the upregulation of protective proteins such as heme oxygenase-1, heat shock proteins, and vascular endothelial growth factor. These molecular responses enhance tissue resilience, promote cellular survival, and improve tolerance to ischemic, inflammatory, and oxidative injuries observed across diverse clinical conditions. This review focuses on HBO-induced protective proteins, synthesizing current knowledge of their molecular mechanisms, expression dynamics, and clinical relevance, as well as the role of exposure protocols in regulating their expression. The findings provide a framework for designing and interpreting future clinical applications of HBO preconditioning.