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Reactive oxygen species (ROS) generation and redox homeostasis refer to the complex biological system that maintains the balance between the production of reactive oxygen species and their neutralization by antioxidant defenses [1.1.1, 1.3.1]. ROS, such as superoxide and hydrogen peroxide, are primarily generated by the mitochondrial electron transport chain and enzymes like NADPH oxidases (NOX) [1.1.1, 1.2.5]. While physiological levels of ROS are essential for signal transduction, cell proliferation, and immune responses, an imbalance leading to excessive ROS—termed oxidative stress—causes damage to DNA, proteins, and lipids [1.2.1, 1.3.4]. This system is a critical therapeutic focus in cancer, where pro-oxidant drugs like doxorubicin and cisplatin are used to overwhelm the antioxidant capacity of tumor cells and induce apoptosis or ferroptosis [1.1.1, 1.5.2]. Conversely, in neurodegenerative and cardiovascular diseases, the goal is often to restore redox balance using antioxidants or Nrf2 activators to prevent oxidative damage [1.3.3, 1.4.2]. However, the dual role of ROS as both signaling molecules and toxic agents presents a significant challenge, as non-specific modulation can interfere with vital cellular processes [1.4.1, 1.5.1].
Drugs targeting this system act by either inducing oxidative stress to trigger cell death (pro-oxidants) or by enhancing antioxidant capacity and scavenging free radicals to prevent tissue damage (antioxidants) [1.1.1, 1.3.2].
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