Mechanisms of pyroptosis in cisplatin ototoxicity based on the NLRP3/Caspase-1/GSDMD pathway
FU Changxue
ZHANG Ya'nan
TIAN Meihui
LIU Huan
SUN Weifang
LI Kun
PENG Houneng
TANG Yong
Abstract：Objective To investigate damaging toxic effects of cisplatin on House Ear Institute-Organ of Corti 1(HEI-OC1)cells and potential mechanisms.Methods In this study,a model of HEI-OC1 cell injury by cisplatin was established.The Caspase-1 inhibitor VX-765 was used as intervention.The CCK-8 method was used to identify cell viability.Flow cytometry,LDH release assay,and AO/EB fluorescence staining were used to examine cellular membrane integrity.ELISA,Western-Blot,immunofluorescence and qRT-PCR were used to demonstrate expression of pyroptosis-related proteins and its mRNAs.Results Compared with the control,cisplatin treated cells demosntrated decreased survival,with some cells showing increased membrane permeability,swelling and deformation or cell membrane rupture.Expression of pyroptosis-related proteins and mRNAs was increased(P<0.05).Compared with cisplatin treatment only,cells treated with VX-765+cisplatin showed increased survival with decreased expression of pyroptosis-related proteins and mRNAs(P<0.05).Conclusions Cisplatin induced death of HEI-OC1 cells in a concentration-dependent manner.Caspase-1-mediated cellular pyroptosis plays an important role in cisplatin-induced ototoxicity,potentially by regulating the NLRP3/Caspase-1/GSDMD pathway.
Keywords：hair cellcisplatinototoxicitypyroptosishearing loss
Publication Date：2025-12-20
Online Publishing Date：2025-12-11(First online date of this platform, not the publication date of the document)
Pages：8( 1045-1052 )