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

Proceedings of the National Academy of Sciences, Journal Year: 2025, Volume and Issue: 122(11)

Published: March 11, 2025

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 regulated cell death dependent on gasdermin D (GSDMD)—was activated in cochleae cisplatin-treated mice, causing CIHL. Meanwhile, treatment with GSDMD inhibitor necrosulfonamide alleviated CIHL these mice. To further examine role GSDMD-mediated pyroptosis CIHL, conducted experiments Gsdmd- deficient mice . Gsdmd −/− significantly lower cochlear damage than control and appeared to be invulnerable Furthermore, stria vascularis (SV), not hair cells (HCs), played a dominant In marginal (MCs) SV, cisplatin induced caspase-dependent cleavage, pore-forming N-terminal rapidly localized mitochondria, leading abnormal mitochondrial aggregation oxidative stress. The consequent dysfunction MCs might result severe progression inflammation, SV damage, HC loss. Notably, pharmacological inhibition using FDA-approved drug disulfiram effectively symptoms Collectively, findings offer broad avenue for inhibiting pyroptosis-induced ototoxicity provide valuable theoretical insights clinical management

Language: Английский

Research Progress of Tinnitus and Neuroinflammation

Journal of Biosciences and Medicines, Journal Year: 2025, Volume and Issue: 13(04), P. 251 - 264

Published: Jan. 1, 2025

Language: Английский

A comprehensive review of the impact of natural products in preventing drug-induced ototoxicity

Inflammopharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: May 8, 2025

Abstract Ototoxicity, the property of certain drugs to cause hearing loss, is a significant concern in medical treatments, particularly with use chemotherapeutic agents like cisplatin and aminoglycosides. These can lead permanent sensorineural loss (SNHL), affecting substantial proportion patients. Existing strategies alleviate these side effects are limited, prompting interest natural products as potential protective agents. Natural being investigated for their ability counteract mechanisms through anti-inflammatory antioxidant properties. The review seeks highlight complementary therapies conventional ototoxic medications, emphasizing roles, which involved cochlear cellular damage programmed cell death. Further research essential establish standardized protocols ensure integration into clinical practice effective therapeutic options.

Language: Английский