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Gu J, Tong L, Lin X, et al. The disruption and hyperpermeability of blood-labyrinth barrier mediates cisplatin-induced ototoxicity. Toxicol Lett. 2021;354:56-64doi: 10.1016/j.toxlet.2021.10.015.
Gu, J., Tong, L., Lin, X., Chen, Y., Wu, H., Wang, X., & Yu, D. (2022). The disruption and hyperpermeability of blood-labyrinth barrier mediates cisplatin-induced ototoxicity. Toxicology letters, 35456-64. https://doi.org/10.1016/j.toxlet.2021.10.015
Gu, Jiayi, et al. "The disruption and hyperpermeability of blood-labyrinth barrier mediates cisplatin-induced ototoxicity." Toxicology letters vol. 354 (2022): 56-64. doi: https://doi.org/10.1016/j.toxlet.2021.10.015
Gu J, Tong L, Lin X, Chen Y, Wu H, Wang X, Yu D. The disruption and hyperpermeability of blood-labyrinth barrier mediates cisplatin-induced ototoxicity. Toxicol Lett. 2022 Jan 01;354:56-64. doi: 10.1016/j.toxlet.2021.10.015. Epub 2021 Oct 29. PMID: 34757176.
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Toxicol Lett. 2022 Jan 01;354:56-64. doi: 10.1016/j.toxlet.2021.10.015. Epub 2021 Oct 29.

The disruption and hyperpermeability of blood-labyrinth barrier mediates cisplatin-induced ototoxicity.

Toxicology letters

Jiayi Gu, Ling Tong, Xin Lin, Yuming Chen, Hao Wu, Xueling Wang, Dehong Yu

Affiliations

  1. Department of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Ear Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China.
  2. Zhongshan Hospital, Fudan University, Shanghai, China.
  3. Department of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Ear Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China. Electronic address: [email protected].
  4. Department of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Ear Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China. Electronic address: [email protected].
  5. Department of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Ear Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China. Electronic address: [email protected].

PMID: 34757176 DOI: 10.1016/j.toxlet.2021.10.015

Abstract

The ototoxic mechanisms of cisplatin on the organ of Corti and spiral ganglion neurons have been extensively studied, while few studies have been focused on the stria vascularis (SV). Herein, we verified the functional and morphological impairment in SV induced by a single injection of cisplatin (12 mg/kg, I.P.), represented by a reduction in Endocochlear Potentials (EP) and strial atrophy, and explored underlying mechanisms. Our results revealed increased extravasation of chromatic tracers (Evans blue dye and FITC-dextran) around microvessels after cisplatin exposure. The increased vascular permeability could be attributed to changes of pericytes (PCs) and perivascular-resident macrophage-like melanocytes (PVM/Ms) in number or morphology, as well as the enhanced level of HIF-1α and downstream VEGF. This capillary leakage led to a high accumulation of cisplatin in the perivascular space in SV, and disrupted the integrity of blood-labyrinth barrier (BLB). Also, tight junction (ZO-1) loosening and Na

Copyright © 2021 Elsevier B.V. All rights reserved.

Keywords: Blood-labyrinth barrier; Cisplatin-induced ototoxicity; Hyperpermeability; Stria vascularis

Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this pa

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