Cisplatin is retained in the cochlea indefinitely following chemotherapy.

Cisplatin is retained in the cochlea indefinitely following chemotherapy.
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DOI:
10.1038/s41467-017-01837-1
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发表时间:
2017-11-21
影响因子:
16.6
通讯作者:
Cunningham LL
Cunningham LL
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Breglio AM;Rusheen AE;Shide ED;Fernandez KA;Spielbauer KK;McLachlin KM;Hall MD;Amable L;Cunningham LL

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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. Permanent hearing loss occurs in many cancer patients treated with cisplatin. In this study, the authors examine cisplatin pharmacokinetics in the cochleae of mice and humans showing that cisplatin is retained for months to years after treatment.
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