Although cisplatin is a widely used chemotherapeutic agent, it is severely toxic and causes irreversible hearing loss, restricting its application in clinical settings. This study aimed to determine the molecular mechanism underlying cisplatin-induced ototoxicity. Here, we established in vitro and in vivo ototoxicity models of cisplatin-induced hair cell loss, and our results showed that reducing STING levels decreased inflammatory factor expression and hair cell death. In addition, we found that cisplatin-induced mitochondrial dysfunction was accompanied by cytosolic DNA, which may act as a critical linker between the cyclic GMP-AMP synthesis-stimulator of interferon genes (cGAS-STING) pathway and the pathogenesis of cisplatin-induced hearing loss. H-151, a specific inhibitor of STING, reduced hair cell damage and ameliorated the hearing loss caused by cisplatin in vivo. This study underscores the role of cGAS-STING in cisplatin ototoxicity and presents H-151 as a promising therapeutic for hearing loss.
Cisplatin/toxicity* ; Animals ; Nucleotidyltransferases/antagonists & inhibitors* ; Membrane Proteins/antagonists & inhibitors* ; Signal Transduction/drug effects* ; Mice ; Hair Cells, Auditory, Inner/pathology* ; Antineoplastic Agents/toxicity* ; Mice, Inbred C57BL ; Hearing Loss/metabolism* ; Male ; Ototoxicity/metabolism*

OBJECTIVETo investigate the influence of N-acetyl-L-cysteine (NAC) on pulmonary injury and oxygen stress caused by smoke inhalation injury.

METHODSRats inflicted with smoke inhalation injury were employed as the model. WBC in BALF (bronchoalveolar lavage fluid), MPO (myeloperoxidase) activity, hydrogen peroxide (H(2)O(2)) content, GSH (glutathione) content and total antioxidant (TAO) capacity in pulmonary tissue were determined.

RESULTSPostinjury WBC in BALF, MPO activity in pulmonary tissue and H(2)O(2) content decreased obviously after NAC treatment. But the pulmonary tissue contents of GSH and ATO increased evidently after the treatment with NAC.

CONCLUSIONNAC treatment could ameliorate pulmonary oxygen stress after smoke inhalation injury. AS a result, the pulmonary antioxidant capacity was improved.

Acetylcysteine ; pharmacology ; Animals ; Bronchoalveolar Lavage Fluid ; Disease Models, Animal ; Free Radical Scavengers ; pharmacology ; Glutathione ; metabolism ; Hydrogen Peroxide ; metabolism ; Leukocytes ; drug effects ; Oxidative Stress ; drug effects ; Peroxidase ; metabolism ; Rats ; Rats, Wistar ; Smoke Inhalation Injury ; enzymology ; metabolism ; pathology