Choi, M.-J.; Kang, H.; Lee, Y.Y.; Choo, O.-S.; Jang, J.H.; Park, S.-H.; Moon, J.-S.; Choi, S.J.; Choung, Y.-H. Cisplatin-Induced Ototoxicity in Rats Is Driven by RIP3-Dependent Necroptosis. Cells2019, 8, 409.
Choi, M.-J.; Kang, H.; Lee, Y.Y.; Choo, O.-S.; Jang, J.H.; Park, S.-H.; Moon, J.-S.; Choi, S.J.; Choung, Y.-H. Cisplatin-Induced Ototoxicity in Rats Is Driven by RIP3-Dependent Necroptosis. Cells 2019, 8, 409.
Choi, M.-J.; Kang, H.; Lee, Y.Y.; Choo, O.-S.; Jang, J.H.; Park, S.-H.; Moon, J.-S.; Choi, S.J.; Choung, Y.-H. Cisplatin-Induced Ototoxicity in Rats Is Driven by RIP3-Dependent Necroptosis. Cells2019, 8, 409.
Choi, M.-J.; Kang, H.; Lee, Y.Y.; Choo, O.-S.; Jang, J.H.; Park, S.-H.; Moon, J.-S.; Choi, S.J.; Choung, Y.-H. Cisplatin-Induced Ototoxicity in Rats Is Driven by RIP3-Dependent Necroptosis. Cells 2019, 8, 409.
Abstract
Cisplatin induces early-onset ototoxicity, resulting in hearing loss. The exact mechanism by which cisplatin causes ototoxicity remains unclear. The purpose of this study was to identify the involvement of receptor-interacting protein kinase(RIP)3-dependent necroptosis in cisplatin-induced ototoxicity in animal models. Sprague–Dawley rats (SD, 8 week) were treated via intraperitoneal (i.p) injection with cisplatin (16 mg/kg for 1 day), and their hearing thresholds were was measured by the auditory brainstem response (ABR) method. Hematoxylin and eosin (H-E) staining, immunohistochemistry, and western blots were performed to determine the effect of cisplatin-induced ototoxicity on cochlear morphology. H-E stains outlined necroptotic changes in the organ of Cortis (OCs) and spiral ganglion neurons (SGNs). Additionally, immunohistochemistry and western blot analysis showed overexpression of RIP3 in the OCs and SGNs that were treated with cisplatin. These results suggest that RIP3-dependent necroptosis was substantial in cisplatin-induced ototoxicity; inner cochlear regions, the OCs, and SGNs were especially sensitive to necroptosis.
Keywords
necroptosis; cisplatin; ototoxicity; organ of corti; spiral ganglion neuron
Subject
Medicine and Pharmacology, Pharmacology and Toxicology
Copyright:
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