Protective effects of MET channels on aminoglycosides- and cisplatin-induced ototoxicity.

Abstract

Aminoglycosides and cisplatin drugs are extensively utilized for their high efficacy in treating various conditions in the clinic, however, their ototoxic side effects warrant significant attention. These drugs could penetrate the inner ear via specific channels or transporters, which not only affect the survival of hair cells but also induce the overproduction of reactive oxygen species. Currently, scientific research mainly addresses this issue through the downstream intervention of reactive oxygen species. However, recent studies have revealed that directly reducing the uptake of these drugs by hair cells can effectively avoid initial damage. In particular, the interactions between drugs and hair cells, as well as the specific functions of relevant channels and transporters, can be explored in detail through the use of molecular dynamics simulations. The swift advancement in the field of structural biology has shed light on the structural functions of various channels and transporters closely related to drug absorption, such as electromechanical transduction channels (MET) and organic cation transporter-2, etc., providing theoretical basis and potential targets for novel ear protection strategies. It is, therefore, imperative to investigate the regulatory role of the MET channel in the up-taking of ototoxic drugs, serving as a pivotal point for the development of preventative and therapeutic approaches. This review aims to highlight the mechanism of inhibition of ototoxic substances absorption by auditory hair cells, explore how to develop novel ear protection methods by targeting these channels and transporters, and provide a new perspective and strategy for addressing drug-induced ototoxicity. The approach to protecting hair cells by targeting these channels and transporters not only broadens our understanding of the underlying mechanisms of ototoxicity, but could also spur further research and progress in the field of auditory protection.