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Nat Commun. 2017 Nov 21;8(1):1654. doi: 10.1038/s41467-017-01837-1.

Cisplatin is retained in the cochlea indefinitely following chemotherapy.

Author information

1
National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD, 20892, USA.
2
Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, OX1 3QX, UK.
3
Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
4
Medical Scientist Training Program, Mayo Clinic School of Medicine, Rochester, MN, 55905, USA.
5
National Institute on Minority Health and Health Disparities, National Institutes of Health, Bethesda, MD, 20892, USA.
6
Electro Scientific Industries, Inc., Bozeman, MT, 59715, USA.
7
National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, 20850, USA.
8
National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD, 20892, USA. lisa.cunningham@nih.gov.

Abstract

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.

PMID:
29162831
PMCID:
PMC5698400
DOI:
10.1038/s41467-017-01837-1
[Indexed for MEDLINE]
Free PMC Article

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