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Cisplatin is retained in the cochlea indefinitely following chemotherapy

Cisplatin chemotherapy causes permanent hearing loss in 40–80% of treated patients. It is unclear whether the cochlea has unique sensitivity to cisplatin or is exposed to higher levels of the drug. Here we use inductively coupled plasma mass spectrometry (ICP-MS) to examine cisplatin pharmacokinetic...

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Autores principales: Breglio, Andrew M., Rusheen, Aaron E., Shide, Eric D., Fernandez, Katharine A., Spielbauer, Katie K., McLachlin, Katherine M., Hall, Matthew D., Amable, Lauren, Cunningham, Lisa L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5698400/
https://www.ncbi.nlm.nih.gov/pubmed/29162831
http://dx.doi.org/10.1038/s41467-017-01837-1
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author Breglio, Andrew M.
Rusheen, Aaron E.
Shide, Eric D.
Fernandez, Katharine A.
Spielbauer, Katie K.
McLachlin, Katherine M.
Hall, Matthew D.
Amable, Lauren
Cunningham, Lisa L.
author_facet Breglio, Andrew M.
Rusheen, Aaron E.
Shide, Eric D.
Fernandez, Katharine A.
Spielbauer, Katie K.
McLachlin, Katherine M.
Hall, Matthew D.
Amable, Lauren
Cunningham, Lisa L.
author_sort Breglio, Andrew M.
collection PubMed
description Cisplatin chemotherapy causes permanent hearing loss in 40–80% of treated patients. It is unclear whether the cochlea has unique sensitivity to cisplatin or is exposed to higher levels of the drug. Here we use inductively coupled plasma mass spectrometry (ICP-MS) to examine cisplatin pharmacokinetics in the cochleae of mice and humans. In most organs cisplatin is detected within one hour after injection, and is eliminated over the following days to weeks. In contrast, the cochlea retains cisplatin for months to years after treatment in both mice and humans. Using laser ablation coupled to ICP-MS, we map cisplatin distribution within the human cochlea. Cisplatin accumulation is consistently high in the stria vascularis, the region of the cochlea that maintains the ionic composition of endolymph. Our results demonstrate long-term retention of cisplatin in the human cochlea, and they point to the stria vascularis as an important therapeutic target for preventing cisplatin ototoxicity.
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spelling pubmed-56984002017-11-24 Cisplatin is retained in the cochlea indefinitely following chemotherapy Breglio, Andrew M. Rusheen, Aaron E. Shide, Eric D. Fernandez, Katharine A. Spielbauer, Katie K. McLachlin, Katherine M. Hall, Matthew D. Amable, Lauren Cunningham, Lisa L. Nat Commun Article Cisplatin chemotherapy causes permanent hearing loss in 40–80% of treated patients. It is unclear whether the cochlea has unique sensitivity to cisplatin or is exposed to higher levels of the drug. Here we use inductively coupled plasma mass spectrometry (ICP-MS) to examine cisplatin pharmacokinetics in the cochleae of mice and humans. In most organs cisplatin is detected within one hour after injection, and is eliminated over the following days to weeks. In contrast, the cochlea retains cisplatin for months to years after treatment in both mice and humans. Using laser ablation coupled to ICP-MS, we map cisplatin distribution within the human cochlea. Cisplatin accumulation is consistently high in the stria vascularis, the region of the cochlea that maintains the ionic composition of endolymph. Our results demonstrate long-term retention of cisplatin in the human cochlea, and they point to the stria vascularis as an important therapeutic target for preventing cisplatin ototoxicity. Nature Publishing Group UK 2017-11-21 /pmc/articles/PMC5698400/ /pubmed/29162831 http://dx.doi.org/10.1038/s41467-017-01837-1 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Breglio, Andrew M.
Rusheen, Aaron E.
Shide, Eric D.
Fernandez, Katharine A.
Spielbauer, Katie K.
McLachlin, Katherine M.
Hall, Matthew D.
Amable, Lauren
Cunningham, Lisa L.
Cisplatin is retained in the cochlea indefinitely following chemotherapy
title Cisplatin is retained in the cochlea indefinitely following chemotherapy
title_full Cisplatin is retained in the cochlea indefinitely following chemotherapy
title_fullStr Cisplatin is retained in the cochlea indefinitely following chemotherapy
title_full_unstemmed Cisplatin is retained in the cochlea indefinitely following chemotherapy
title_short Cisplatin is retained in the cochlea indefinitely following chemotherapy
title_sort cisplatin is retained in the cochlea indefinitely following chemotherapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5698400/
https://www.ncbi.nlm.nih.gov/pubmed/29162831
http://dx.doi.org/10.1038/s41467-017-01837-1
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