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Non-specific biomolecules via ROS/LOPs refers to the broad array of cellular components, including genomic DNA, functional proteins, and membrane lipids, that serve as substrates for oxidative modification by Reactive Oxygen Species (ROS) and Lipid Oxidation Products (LOPs) [Halliwell & Gutteridge, 2015]. This interaction is characterized by a lack of specificity, where highly reactive intermediates like hydroxyl radicals or lipid peroxyl radicals cause irreversible structural damage, such as DNA strand breaks, protein carbonylation, and lipid peroxidation [NIH, 2023]. In oncology, this mechanism is intentionally triggered by therapies like radiation, photodynamic therapy, and certain chemotherapeutic agents to induce cell death in malignant tissues [PubMed, 2021]. Additionally, in the context of medical ozone therapy, the generation of LOPs acts as a transient oxidative stressor that modulates various biological pathways by reacting with these biomolecules [Bocci, 2011]. However, in chronic conditions like neurodegeneration and cardiovascular disease, the uncontrolled oxidation of these biomolecules drives disease progression and tissue degradation [StatPearls, 2023]. From a drug development perspective, targeting these molecules presents a significant challenge due to the difficulty in achieving site-specific oxidation without causing systemic toxicity [PubMed, 2020].
Induction of non-specific oxidative damage to cellular macromolecules (DNA, proteins, and lipids) through the generation of reactive oxygen species (ROS) and lipid oxidation products (LOPs) [Halliwell & Gutteridge, 2015; Bocci, 2011].
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