Cisplatin and oxaliplatin are toxic to cochlear outer hair cells and both target thioredoxin reductase in organ of Corti cultures.
Cisplatin and oxaliplatin are toxic to cochlear outer hair cells and both target thioredoxin reductase in organ of Corti cultures.
复制标题
DOI：
10.3109/00016489.2013.879740
复制
发表时间：
2014-05
影响因子：
1.4
通讯作者：
Kirkegaard M
中科院分区：
文献类型：
--
作者：
Dammeyer P;Hellberg V;Wallin I;Laurell G;Shoshan M;Ehrsson H;Arnér ES;Kirkegaard M
硫氧还蛋白还原酶（TrxR）的抑制可能是顺铂诱导耳毒性的一个因素。直接暴露于顺铂和奥沙利铂的Corti器官使毛细胞损失相等。已知含铂药物针对癌细胞中的抗氧化硒蛋白TrxR。这两种含铂的抗癌药物，顺铂和奥沙利铂，有不同的副作用。只有顺铂引起听力损失，即有奥沙利铂治疗后未见的耳毒性副作用。本研究的目的是评估TrxR是否为耳蜗中的靶标。当顺铂和奥沙利铂直接给药于Corti器官时，也比较了外毛细胞的损失。Corti细胞培养器官直接暴露于顺铂和奥沙利铂。检测毛细胞及TrxR水平。进行TrxR免疫组化染色。采用动物模型评价顺铂和奥沙利铂在体内治疗后对TrxR的影响。将耳蜗器官型培养物直接暴露于顺铂或奥沙利铂诱导相当水平的外毛细胞损失和TrxR抑制，表明如果耳蜗直接暴露于顺铂或奥沙利铂，这两种药物具有相似的耳毒性。
Inhibition of thioredoxin reductase (TrxR) may be a contributing factor in cisplatin-induced ototoxicity. Direct exposure of organ of Corti to cisplatin and oxaliplatin gives equal loss of hair cells. Platinum-containing drugs are known to target the anti-oxidant selenoprotein TrxR in cancer cells. Two such anti-cancer, platinum-containing drugs, cisplatin and oxaliplatin, have different side effects. Only cisplatin induces hearing loss, i.e. has an ototoxic side effect that is not seen after treatment with oxaliplatin. The objective of this study was to evaluate if TrxR is a target in the cochlea. Loss of outer hair cells was also compared when cisplatin and oxaliplatin were administered directly to the organ of Corti. Organ of Corti cell culture was used for direct exposure to cisplatin and oxaliplatin. Hair cells were evaluated and the level of TrxR was assessed. Immunohistochemical staining for TrxR was performed. An animal model was used to evaluate the effect on TrxR after treatment with cisplatin and oxaliplatin in vivo. Direct exposure of cochlear organotypic cultures to either cisplatin or oxaliplatin induced comparable levels of outer hair cell loss and inhibition of TrxR, demonstrating that both drugs are similarly ototoxic provided that the cochlea becomes directly exposed.
登录
查看更多内容
影响因子：
3.7
作者：
Anestål K;Prast-Nielsen S;Cenas N;Arnér ES
通讯作者：
Arnér ES
影响因子：
6
作者：
Ciarimboli, Giuliano;Deuster, Dirk;Schlatter, Eberhard
通讯作者：
Schlatter, Eberhard
影响因子：
7.4
作者：
Arnér, ESJ;Nakamura, H;Spyrou, G
通讯作者：
Spyrou, G
影响因子：
45.3
作者：
Knight, Kristin R.;Kraemer, Dale F.;Neuwelt, Edward A.
通讯作者：
Neuwelt, Edward A.
影响因子：
4.8
作者：
Sun, QA;Zappacosta, F;Gladyshev, VN
通讯作者：
Gladyshev, VN