GSDMD-mediated mitochondrial dysfunction in marginal cells: A potential driver of inflammation and stria vascularis damage in CIHL.

ABSTRACT: Inflammation is among the known causes of cisplatin-induced hearing loss (CIHL), but its exact pathophysiological mechanisms remain unclear. Herein, we demonstrated that pyroptosis-a recently identified inflammatory type of regulated cell death dependent on gasdermin D (GSDMD)-was activated in the cochleae of cisplatin-treated mice, causing CIHL. Meanwhile, treatment with the GSDMD inhibitor necrosulfonamide alleviated CIHL in these mice. To further examine the role of GSDMD-mediated pyroptosis in CIHL, we conducted experiments in Gsdmd-deficient mice. Gsdmd^-/- mice demonstrated significantly lower cisplatin-induced cochlear damage than control mice and appeared to be invulnerable to CIHL. Furthermore, GSDMD-mediated pyroptosis in the stria vascularis (SV), but not

SUBMITTER: Xiao Y 

PROVIDER: S-EPMC11929501 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature