Declassification of the neurotoxic mechanism of cisplatin - caused by necrotity withering from RIP3-mediated

Cancer in the global incidence of increasing incidence, chemotherapy in the treatment of malignant tumors is indispensable, cisplatin, also known as cofamine, for the current commonly used metal platinum complex, anti-cancer spectrum, clinical lying is mainly used to treat head and neck squamous cell carcinoma, ovarian cancer, testicular cancer and bladder, esophageal, lung and other parts of the epithelial cell carcinoma, is currently quite effective chemotherapy drugs, the treatment of tumors also has a sensitive effectHowever, the use of cisplatin treatment, but also can not ignore the fact that cisplatin has some side effects, such as malignant vomiting, nephrotoxicity, neurotoxicity and ear toxicityCisplatin can lead to hearing problems, such as cisplatin in children's high-risk neuroblastoma (NB) clinical chemotherapy use, a study shows that 67 cases of high-risk neuroblastoma children, hearing damage rate of 16.41% significantly higher than before treatment, cisplatin can cause light moderate hearing damageAbout 60%-80% of patients in the application of cisplatin chemotherapy when the hearing threshold increased, about 15% of patients have severe hearing impairment, and this hearing loss is often two-sided, irreversible, hearing loss often occurs in the high-frequency zone of 4000-8000 Hz, and gradually to the medium- and low-frequency area of hearing, and the more times to receive chemotherapy hearing damage, so the more toxic ear is affected by the treatment of the diseasecell death includes apoptosis, necrosis, and necrosisApoptosis is apoptosis process initiated by apoptosis-related genes involved in a variety of physiological pathology factors, and many inflammatory media and cytokines affect the apoptosis processNecrosis is a passive process, and necrosis apoptosis is a new way of cell deathA recent study published in the journal Cells found that the neurotoxicity of cisplatin is caused by Apoptotic necrosis mediated by RIP3in the past, although the effects of cisplatin on hearing have been recognized, the specific mechanism sits not clearlyThe experiment used 8-week-old SD rats, injected with cisplatin (16 mg/kg) daily through the abdominal cavity, followed by ABR assays, HE staining, immunohistization and immunoprinting, and used necrotizing apoptosticin 1 (Nec-1) and apoptosis inhibitor Z-VAD in the HEI-OC1 cell lineHE staining shows an increase in apoptosis necrosis of the helix nerve knotImmune histology and immunoprinting showed an increase in RIP3 protein levels in the helix nerve section after cisplatin therapyThe addition of RIP1 selective inhibitor Nec-1 significantly inhibited cell death caused by cisplatin, while adding Z-VAD did not alter cell death caused by cisplatinThe results show that RIP3-mediated necrotity apoptosis is essential for cell death caused by cisplatinThe cochlear implants and spiral nerve sections of the inner ear are susceptible to necrosis witheringThere have been many reports in the past that there is a close relationship between reactive oxygen and hair apoptosis, but the exact mechanism is unknown, and whether necrosis apoptosis is related to reactive oxygen is still unknownThe mechanism of the internal ear toxicity caused by cisplatin has not yet been fully clarified, and its effect on cochlear alcoe form is mainly manifested in the outer hair cells, vascular lines and helical nerve sections of The Corti device, which seriously affects the quality of life of many tumor patients after their recovery The mechanism of cisplatin-induced internal ear toxicity has not yet been fully clarified, and only by constantly excavating its intrinsic mechanism can effective treatments be found to reduce the occurrence of side effects and improve the quality of life for chemotherapy patients reference source: Mi-Jin Choi, Hyunsook Kang, Yun Yeong Lee, et al Cisplatin-Induced Ototoxicity in Rats Is Driven by RIP3-Dependent Necroptosis Cells 2019, 8,409.