Cisplatin-induced ototoxicity pathway

The "Cisplatin-induced ototoxicity pathway" refers to a collection of molecular mechanisms by which cisplatin—a widely used chemotherapeutic agent—causes permanent hearing loss. This is not a single molecule or receptor but rather a complex network involving multiple cellular processes within the inner ear. After entering the cochlea through blood-labyrinth barriers via transporters such as copper transporter protein 1 (CTR1) and organic cation transporter protein 2 (OCT2), cisplatin accumulates in hair cells where it forms toxic DNA adducts that trigger apoptosis through p53 activation, mitochondrial dysfunction, release of cytochrome c, caspase cascade activation, oxidative stress from excessive ROS generation via NADPH oxidase/xanthine oxidase activity, lipid peroxidation, ferroptosis pathways, and induction of inflammatory responses mediated by STAT1-regulated genes like COX‑2 and TNF‑α. These events culminate in irreversible sensory hair cell death leading to sensorineural hearing loss. While several antioxidants or anti-inflammatory agents have shown protective effects experimentally—such as melatonin or silymarin—no definitive clinical prevention strategy exists yet for this adverse effect associated with platinum-based chemotherapy drugs like cisplatin.[1][3][5]

Other names

Cisplatin ototoxicity pathwayPlatinum-based drug-induced hearing loss pathwayCisplatin-associated cochlear toxicity mechanism

For cisplatin and related drugs causing ototoxicity: - Formation of DNA adducts leading to DNA damage and activation of apoptotic pathways[1][5][7] - Generation of reactive oxygen species (ROS), resulting in oxidative stress and cell death in cochlear cells[2][5][6][7] - Activation of inflammatory signaling cascades, including upregulation of COX‑2, iNOS, TNF‑α via STAT1 activation[1][7]