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Cellular and tissue components exposed to medical ozone represent the primary biochemical environment where ozone exerts its therapeutic effects. Upon administration, ozone (O3) does not target a specific receptor but instead reacts instantaneously with polyunsaturated fatty acids (PUFAs), water, and antioxidants present in plasma or interstitial fluids (Bocci, 2006). This chemical interaction generates transient reactive oxygen species (ROS), such as hydrogen peroxide (H2O2), and more stable lipid oxidation products (LOPs), including 4-hydroxynonenal (4-HNE) (Sagai & Bocci, 2011). These secondary messengers subsequently interact with various cell types, such as erythrocytes to improve oxygen delivery and leukocytes to modulate the immune response (Elvis & Ekta, 2011). Furthermore, LOPs can activate the Nrf2/ARE pathway, leading to the up-regulation of endogenous antioxidant enzymes like superoxide dismutase and glutathione peroxidase (Smith et al., 2017). While used therapeutically for conditions like chronic wounds, infections, and ischemic disorders, precise dosing is critical to avoid overwhelming the body's antioxidant capacity (Bocci et al., 2009). Inhalation of ozone is strictly avoided due to the lack of antioxidant protection in the lung's alveolar surface liquid, which leads to severe respiratory toxicity (NIH, 2023). Overall, these components serve as the substrate for a controlled oxidative stress that triggers beneficial biological adaptations.
Ozone reacts with polyunsaturated fatty acids and water in biological fluids to generate reactive oxygen species (ROS) and lipid oxidation products (LOPs), which act as secondary messengers to activate Nrf2-mediated antioxidant responses and modulate cytokine production.
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