Cisplatin-induced vestibular hair cell lesion-less damage at high doses
Cisplatin, a widely used anticancer drug, damages hair cells in cochlear organotypic cultures at low doses, but paradoxically causes little damage at high doses resulting in a U-shaped dose-response function. To determine if the cisplatin dose-response function for vestibular hair cells follows a si...
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2018-12-01
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| Series: | Journal of Otology |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1672293018300527 |
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doaj-34b544fbda0a47deac79e356a951c3802020-11-25T00:21:32ZengElsevierJournal of Otology1672-29302018-12-01134115121Cisplatin-induced vestibular hair cell lesion-less damage at high dosesDalian Ding0Haiyan Jiang1Jianhui Zhang2Xianrong Xu3Weidong Qi4Haibo Shi5Shankai Yin6Richard Salvi7Center for Hearing and Deafness, University at Buffalo, USA; Department of Otolaryngology Head and Neck Surgery, Huashan Hospital, Fudan University, Shanghai, China; Corresponding author. Center for Hearing and Deafness, University at Buffalo, USA.Center for Hearing and Deafness, University at Buffalo, USADepartment of Otolaryngology Head and Neck Surgery, The Third People’s Hospital of Chengdu, ChinaAir Force General Hospital, Beijing, ChinaDepartment of Otolaryngology Head and Neck Surgery, Huashan Hospital, Fudan University, Shanghai, ChinaDepartment of Otorhinolaryngology, Affiliated Sixth People’s Hospital of Shanghai Jiaotong University, Shanghai, ChinaDepartment of Otorhinolaryngology, Affiliated Sixth People’s Hospital of Shanghai Jiaotong University, Shanghai, ChinaCenter for Hearing and Deafness, University at Buffalo, USA; Department of Audiology and Speech-Language Pathology, Asia University, ChinaCisplatin, a widely used anticancer drug, damages hair cells in cochlear organotypic cultures at low doses, but paradoxically causes little damage at high doses resulting in a U-shaped dose-response function. To determine if the cisplatin dose-response function for vestibular hair cells follows a similar pattern, we treated vestibular organotypic cultures with doses of cisplatin ranging from 10 to 1000 μM. Vestibular hair cell lesions progressively increased as the dose of cisplatin increased with maximum damage occurring around 50–100 μM, but the lesions progressively decreased at higher doses resulting in little hair cell loss at 1000 μM. The U-shaped dose-response function for cisplatin-treated vestibular hair cells in culture appears to be regulated by copper transporters, Ctr1, ATP7A and ATP7B, that dose-dependently regulate the uptake, sequestration and extrusion of cisplatin. Keywords: Cisplatin, Ototoxicity, Copper transporters, Vestibular organotypic cultureshttp://www.sciencedirect.com/science/article/pii/S1672293018300527 |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Dalian Ding Haiyan Jiang Jianhui Zhang Xianrong Xu Weidong Qi Haibo Shi Shankai Yin Richard Salvi |
| spellingShingle |
Dalian Ding Haiyan Jiang Jianhui Zhang Xianrong Xu Weidong Qi Haibo Shi Shankai Yin Richard Salvi Cisplatin-induced vestibular hair cell lesion-less damage at high doses Journal of Otology |
| author_facet |
Dalian Ding Haiyan Jiang Jianhui Zhang Xianrong Xu Weidong Qi Haibo Shi Shankai Yin Richard Salvi |
| author_sort |
Dalian Ding |
| title |
Cisplatin-induced vestibular hair cell lesion-less damage at high doses |
| title_short |
Cisplatin-induced vestibular hair cell lesion-less damage at high doses |
| title_full |
Cisplatin-induced vestibular hair cell lesion-less damage at high doses |
| title_fullStr |
Cisplatin-induced vestibular hair cell lesion-less damage at high doses |
| title_full_unstemmed |
Cisplatin-induced vestibular hair cell lesion-less damage at high doses |
| title_sort |
cisplatin-induced vestibular hair cell lesion-less damage at high doses |
| publisher |
Elsevier |
| series |
Journal of Otology |
| issn |
1672-2930 |
| publishDate |
2018-12-01 |
| description |
Cisplatin, a widely used anticancer drug, damages hair cells in cochlear organotypic cultures at low doses, but paradoxically causes little damage at high doses resulting in a U-shaped dose-response function. To determine if the cisplatin dose-response function for vestibular hair cells follows a similar pattern, we treated vestibular organotypic cultures with doses of cisplatin ranging from 10 to 1000 μM. Vestibular hair cell lesions progressively increased as the dose of cisplatin increased with maximum damage occurring around 50–100 μM, but the lesions progressively decreased at higher doses resulting in little hair cell loss at 1000 μM. The U-shaped dose-response function for cisplatin-treated vestibular hair cells in culture appears to be regulated by copper transporters, Ctr1, ATP7A and ATP7B, that dose-dependently regulate the uptake, sequestration and extrusion of cisplatin. Keywords: Cisplatin, Ototoxicity, Copper transporters, Vestibular organotypic cultures |
| url |
http://www.sciencedirect.com/science/article/pii/S1672293018300527 |
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