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The reactive oxygen species (ROS) and reactive nitrogen species (RNS) pool consists of highly reactive molecules, such as superoxide, hydrogen peroxide, hydroxyl radicals, nitric oxide, and peroxynitrite, which are generated through mitochondrial metabolism and enzymatic activities of NADPH oxidases (NOX) and nitric oxide synthases (NOS) [1.3.1, 1.5.4]. At physiological levels, these species serve as critical signaling mediators in processes like vasodilation, immune defense, and gene expression regulation [1.3.2, 1.5.1]. However, an imbalance known as oxidative or nitrosative stress leads to the damage of cellular macromolecules, including DNA, proteins, and lipids, contributing to the pathogenesis of cancer, neurodegenerative diseases, and cardiovascular disorders [1.2.2, 1.4.2]. Therapeutic interventions target this pool either by using antioxidants and scavengers like edaravone and N-acetylcysteine to mitigate damage, or by employing pro-oxidants like cisplatin to overwhelm cancer cell defenses and induce apoptosis [1.1.2, 1.3.5]. A major challenge in targeting the ROS/RNS pool is its double-edged sword nature, where non-selective suppression can disrupt essential redox signaling or lead to reductive stress [1.3.2, 1.4.1].
Drugs targeting the ROS/RNS pool act by directly scavenging and neutralizing reactive species, inhibiting the enzymes responsible for their production (e.g., NOX, XO), or inducing their accumulation to toxic levels to promote cell death in cancer cells.
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