Hyperbaric oxygen therapy and N-acetylcysteine: a redox-dependent interaction

Hyperbaric oxygen therapy (HBOT) is widely used in clinical medicine and exerts its therapeutic effects primarily by modulating cellular redox signaling. Acute exposure to hyperbaric hyperoxia induces a transient increase in reactive oxygen species (ROS), which can initiate adaptive antioxidant responses and activate cytoprotective pathways. However, excessive ROS generation may also contribute to oxidative injury, depending on the treatment protocol and underlying pathological state. N-acetylcysteine (NAC), a precursor of glutathione and a widely used antioxidant, has therefore been investigated as a potential adjunct therapy to modulate HBOT-induced oxidative responses. This mini-review summarizes current evidence regarding the interaction between HBOT and NAC in experimental and clinical studies. The available studies indicate that the combined effects of HBOT and NAC are context-dependent. In conditions characterized by severe oxidative stress, NAC may enhance the therapeutic effects of HBOT by reducing pathological ROS accumulation and improving antioxidant capacity. In contrast, in models where ROS act as signaling molecules that trigger adaptive or regenerative pathways, antioxidant intervention may attenuate or abolish the beneficial effects of HBOT. Evidence also suggests that treatment timing, dosage, and baseline oxidative status may modify the outcomes of combined therapy. Overall, the interaction between HBOT and NAC reflects a delicate balance between pathological oxidative stress and redox-dependent signaling mechanisms. A better understanding of these dynamics may help optimize therapeutic strategies involving hyperbaric oxygen and antioxidant modulation in clinical practice.