Reactive oxygen species-related redox cycling (ROS redox cycling)

Reactive oxygen species (ROS)-related redox cycling is a biochemical process characterized by the repeated reduction and oxidation of a molecule, resulting in the catalytic generation of ROS such as superoxide radicals and hydrogen peroxide (Kovacic & Somanathan, 2014, 'Mechanisms of toxicity by redox cycling drugs'). This cycle is often initiated by cellular enzymes like NADPH-cytochrome P450 reductase or NADH dehydrogenase, which transfer an electron to a substrate—typically a quinone, nitro compound, or metal complex—to form a reactive radical (Monks et al., 1992, 'Quinone chemistry and toxicity'). In the presence of molecular oxygen, this radical is rapidly re-oxidized to the parent compound, transferring the electron to oxygen and creating a superoxide anion. This mechanism is a double-edged sword in pharmacology; it is utilized by certain chemotherapeutic agents like Doxorubicin to induce oxidative stress-mediated apoptosis in malignant cells, but it is also a primary driver of drug-induced toxicities, such as anthracycline-induced cardiomyopathy and paraquat-induced pulmonary fibrosis (Bolton et al., 2000, 'Role of quinones in toxicology'). Because it describes a chemical cycle rather than a specific protein or receptor, it is classified as a mechanism of action or toxicological pathway rather than a therapeutic target molecule. Understanding this process is essential for developing strategies to mitigate oxidative damage in healthy tissues during treatment.

Other names

Redox cyclingROS generationOxidative stress inductionQuinone redox cyclingOne-electron reduction-oxidation cycle

Drugs or xenobiotics undergo enzymatic one-electron reduction (typically by NADPH-cytochrome P450 reductase) to form a reactive radical intermediate, which then reacts with molecular oxygen to regenerate the parent compound and produce a superoxide radical (O2•-), creating a continuous catalytic cycle of ROS production (Kovacic & Somanathan, 2014).