Deferoxamine protects cochlear hair cells and hair cell-like HEI-OC1 cells against tert-butyl hydroperoxide-induced ototoxicity.

Oxidative stress is the common mechanism of sensorineural hearing loss (SNHL) caused by many factors, such as noise, drugs and ageing. Here, we used tert-butyl hydroperoxide (t-BHP) to cause oxidative stress damage in HEI-OC1 cells and in an in vitro cochlear explant model. We observed lipid peroxidation, iron accumulation, mitochondrial shrinkage and vanishing of mitochondrial cristae, which caused hair cell ferroptosis, after t-BHP exposure. Moreover, the number of TUNEL-positive cells in cochlear explants and HEI-OC1 cells increased significantly, suggesting that t-BHP caused the apoptosis of hair cells. Administration of deferoxamine (DFOM) significantly attenuated t-BHP-induced hair cell loss and disordered hair cell arrangement in cochlear explants as well as HEI-OC1 cell death, including via apoptosis and ferroptosis. Mechanistically, we found that DFOM treatment reduced t-BHP-induced lipid peroxidation, iron accumulation and mitochondrial pathological changes in hair cells, consequently mitigating apoptosis and ferroptosis. Moreover, DFOM treatment alleviated GSH depletion caused by t-BHP and activated the Nrf2 signalling pathway to exert a protective effect. Furthermore, we confirmed that the protective effect of DFOM mainly depended on its ability to chelate iron by constructing Fth1 knockout (KO), TfR1 KO and Nrf2 KO HEI-OC1 cell lines using CRISPR/Cas9 technology and a Flag-Fth1 (overexpression) HEI-OC1 cell line using the FlpIn™ System. Our findings suggest that DFOM is a potential drug for SNHL treatment due to its ability to inhibit apoptosis and ferroptosis by chelating iron and scavenging reactive oxygen species (ROS).

[Clinicopathological features of primary seminal vesicle adenocarcinoma: A report of 4 cases and review of the literature].

OBJECTIVE: To investigate the clinicopathological characteristics, diagnosis, and treatment of primary seminal vesicle adenocarcinoma (SVAC). METHODS: We analyzed the clinical data and clinicopathological characteristics of 4 cases of primary SVAC treated in the Department of Urology of the Second Hospital of Tianjin Medical University and reviewed relevant literature. RESULTS: All the 4 patients were treated by open radical resection of the seminal vesicle and prostate and pathologically diagnosed with SVAC. Preoperative prostatic biopsy had shown 1 of the cases to be negative, while preoperative CT and transrectal ultrasound had revealed a huge pelvic cystic neoplasm in another patient. Immunohistochemistry manifested that the 4 cases were all negative for prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), and cytokeratin 20 (CK20), but positive for cancer antigen 125 (CA125) and CK7. All the patients recovered smoothly after surgery and experienced no recurrence or metastasis during 154, 41, 20, and 12 months of follow-up. CONCLUSIONS: Primary seminal vesicle carcinoma is extremely rare and presents in an advanced stage. Immunohistochemistry plays a valuable role in its differential diagnosis. Various combinations of radical surgery, radiotherapy, androgen-deprivation therapy, and chemotherapy are recommended for the treatment of the disease.