Inhalation of hydrogen gas attenuates cisplatin-induced ototoxicity via reducing oxidative stress

Inhalation of hydrogen gas attenuates cisplatin-induced ototoxicity via reducing oxidative stress
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吸入氢气可通过减少氧化应激来减轻顺铂引起的耳毒性。

DOI:
10.1016/j.ijporl.2011.10.014
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发表时间:
2012-01-01
影响因子:
1.5
通讯作者:
Qiu, Jianhua
Qiu, Jianhua
中科院分区:
医学4区
文献类型:
--
作者:
Qu, Juan;Li, Xu;Qiu, Jianhua

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目的:顺铂是一种广泛用于治疗多种肿瘤的抗癌药物,具有由活性氧(ROS)诱导的强烈耳毒性副作用。最近有报道称,氢气(H-2)是一种新型抗氧化剂,可以选择性地还原细胞毒性最强的活性氧自由基--羟基自由基。本研究旨在探讨H-2治疗是否有利于顺铂诱导的耳毒性,通过减少oxidizedstress.Methods:动物腹腔注射顺铂16 mg/kg或相同体积的生理盐水30 min。分别于顺铂或生理盐水注射后1 h和6 h开始给予2% H-2吸入60 min。采用听性脑干反应(ABR)评价各组动物的听力状况。鬼笔环肽染色观察毛细胞损伤情况。此外,血清和耳蜗组织中的氧化产物的水平进行了measured.Results:我们发现,H-2治疗显着衰减顺铂引起的听力损失评价点击诱发和短纯音ABR阈值。此外,组织学分析表明,2%H-2治疗显着减轻顺铂诱导的毛细胞损伤的器官的corti。此外,顺铂可显著升高血清和耳蜗组织中丙二醛(MDA)和8-iso-PGF 2 α(8-iso-PGF 2 α)的水平,而H-2处理可降低上述水平。结论:H-2可通过减轻氧化应激而减轻顺铂所致的耳毒性。因此。H-2通过有效减轻顺铂的耳毒性,有可能改善化疗期间患者的生活质量。(C)2011爱思唯尔爱尔兰有限公司保留所有权利。
Objective: Cisplatin, an anticancer drug used extensively to treat a broad range of tumors, has strong ototoxic side effects induced by reactive oxygen species (ROS). Recently, it has been reported that hydrogen gas (H-2) is a new antioxidant by selectively reducing hydroxyl radical, the most cytotoxic ROS. The present study was designed to investigate whether H-2 treatment is beneficial to cisplatin-induced ototoxicity via reducing oxidative stress.Methods: The animals were intraperitoneally given a 30 min infusion of 16 mg/kg cisplatin or the same volume of saline. H-2 treatment was given twice with 2% H-2 inhalation for 60 min starting at 1 h and 6 h after cisplatin or saline injection, respectively. The hearing status of all animals was evaluated by auditory brainstem responses (ABR). The hair cell damage was observed by phalloidin staining. In addition, the levels of oxidative products in serum and cochlear tissue were measured.Results: We found that H-2 treatment significantly attenuated cisplatin-induced hearing loss evaluated by click-evoked and tone burst ABR threshold. Furthermore, histological analysis revealed that 2% H-2 treatment significantly alleviated cisplatin-induced hair cell damage in the organ of corti. In addition, cisplatin significantly increased the levels of malondialdehyde (MDA) and 8-iso-prostaglandin F2 alpha (8-iso-PGF2 alpha) in serum and cochlear tissue, which was attenuated by H-2 treatment.Conclusion: These results demonstrate that H-2 is beneficial to cisplatin-induced ototoxicity via reducing oxidative stress. Therefore. H-2 has potential for improving the quality of life of patients during chemotherapy by efficiently mitigating the cisplatin ototoxicity. (C) 2011 Elsevier Ireland Ltd. All rights reserved.