Beyond Paradox: Ozone Therapy as a Hormetic Modulator in Ischemia-Reperfusion Injury - An Update

Area of Science:

• Biomedical science
• Therapeutic research
• Oxidative stress and inflammation

Background:

• Ischemia-reperfusion injury (IRI) is a major clinical problem linked to mitochondrial dysfunction and redox imbalance.
• Ozone therapy, once viewed as harmful, is now recognized for its therapeutic potential via hormesis.
• Controlled ozone administration exhibits dose-dependent effects.

Purpose of the Study:

• To critically analyze the emerging role of ozone therapy in managing IRI.
• To evaluate ozone's hormetic properties and their impact on cellular stress responses.
• To identify research gaps and future directions for clinical translation.

Main Methods:

• Review of recent research on ozone therapy and IRI.
• Quantitative analysis of low-dose ozone effects on oxidative stress markers and antioxidant enzymes.
• Assessment of protective mechanisms involving Nrf2 and NF-κB pathways.
• Evaluation of evidence across cardiovascular, digestive, urogenital, and cerebral systems.

Main Results:

• Low-dose ozone (10-40 µg/mL) significantly reduces oxidative stress and enhances antioxidant activity.
• Ozone therapy upregulates protective enzymes via Nrf2 and suppresses NF-κB-mediated inflammation.
• Consistent protective effects observed across multiple organ systems with moderate to large effect sizes.
• Therapeutic window identified: beneficial effects at 10-40 µg/mL, potential toxicity above 80 µg/mL.

Conclusions:

• Ozone therapy demonstrates promising experimental efficacy in IRI through hormetic modulation.
• Significant limitations exist, including reliance on animal models and lack of standardized protocols.
• Further research is crucial, focusing on optimal dosing, administration, safety, and well-designed human trials for clinical application.