Korean J Otorhinolaryngol-Head Neck Surg.  2022 Oct;65(10):569-579. 10.3342/kjorl-hns.2022.00507.

Cisplatin-Induced Ototoxicity: Updates on Potential Molecular Mechanism

• Jung DJ

• KMID: 2534445
• DOI: http://doi.org/10.3342/kjorl-hns.2022.00507

Abstract

Cis-diamminedichloroplatinum(II) (cisplatin), platinum compound, is an anti-cancer agent currently used for the treatment of a number of human solid cancers. It irreversibly reacts with DNA to form an interconnection between guanine-group helices, resulting in cell death. Furthermore, it is also associated with numerous adverse effects such as nephrotoxicity, neurotoxicity, and ototoxicity. Hearing loss due to cisplatin ototoxicity is usually permanent and bilateral. Many studies have been conducted on the ototoxicity of cisplatin, however, its pathology and treatment have not been fully elucidated. Studies have reported that cisplatin inhibits the action of adenylate cyclase in the stria vascularis, and hearing loss occurs due to a decrease in the receptor current of the outer hair cells. In addition, it has been reported that morphological changes in the inner ear include changes in outer hair cells and abnormal findings in the supporting cells of the organ of Corti and Reissner’s membrane. Oxidative stress is known to be the main cause of ototoxicity. In addition, it has recently been suggested that inflammation may trigger inner ear cell death through autophagy, necrosis, and endogenous apoptosis. In this review, we intend to provide a basis for the prevention strategy of cisplatin-induced ototoxicity by revealing its molecular targets and intracellular pathways.

Keyword

Cisplatin; Mechanism; Ototoxicity