Cellular membranes and macromolecules (Reactive Oxygen Species-mediated damage) (ROS-mediated cellular damage)

Cellular membranes and macromolecules via ROS generation refers to a broad cytotoxic mechanism rather than a single molecular target like a receptor or enzyme. This process involves the production of reactive oxygen species (ROS)—including superoxide radicals, hydrogen peroxide, and hydroxyl radicals—which chemically attack and degrade essential cellular components (Sies & Jones, 2020, Nature Reviews Molecular Cell Biology). Key substrates of this oxidative assault include polyunsaturated fatty acids in the lipid bilayer, leading to lipid peroxidation; amino acid residues in proteins, causing misfolding or inactivation; and nitrogenous bases in DNA, resulting in mutations or strand breaks (Moloney & Cotter, 2018, Seminars in Cell & Developmental Biology). In clinical practice, this mechanism is exploited by several classes of chemotherapeutics, such as anthracyclines and platinum-based agents, as well as ionizing radiation and photodynamic therapy, to induce apoptosis in malignant cells (NIH/NCI, 2023). However, because ROS-mediated damage is often non-specific, it can lead to significant off-target toxicities, such as the dose-limiting cardiotoxicity observed with doxorubicin (PubChem, 2024). Consequently, while ROS generation is a potent therapeutic tool for eliminating diseased cells, managing the balance between therapeutic oxidative stress and systemic damage remains a primary challenge in drug development.

Other names

Oxidative stress-induced damageROS-induced lipid peroxidationOxidative modification of macromoleculesReactive oxygen species generation

Induction of oxidative stress through the generation of reactive oxygen species (ROS), which leads to the chemical modification and degradation of lipids, proteins, and nucleic acids, ultimately resulting in loss of cellular integrity and activation of programmed cell death pathways.