Targeting nitrative stress for attenuating cisplatin-induced downregulation of cochlear LIM domain only 4 and ototoxicity

Schematic representation of the role of nitrative stress and LMO4 downregulation in cisplatin-induced ototoxicity. Cisplatin is known to induce cochlear oxidative stress by activating NOX3. The cisplatin-induced generation of reactive oxygen species eventually leads to the nitration of LMO4 and decreases its level in the cochlea. Generally, LMO4 acts as a scaffold for protein complexes and regulates cellular apoptosis. The cisplatin-induced decrease in LMO4 probably compromises the LMO4 associated anti-apoptotic machinery and thereby facilitates cochlear apoptosis and ototoxicity.