New insight in colistin induced neurotoxicity with the mitochondrial dysfunction in mice central nervous tissues
New insight in colistin induced neurotoxicity with the mitochondrial dysfunction in mice central nervous tissues
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关于粘菌素诱导小鼠中枢神经组织线粒体功能障碍的神经毒性的新见解
DOI：
10.1016/j.etp.2013.01.008
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发表时间：
2013-09-01
影响因子：
--
通讯作者：
Li, Jian
中科院分区：
文献类型：
--
作者：
Dai, Chongshan;Li, Jichang;Li, Jian
本研究以小鼠为实验动物，分别经尾静脉给予硫酸粘杆菌素15（分两次给药，间隔12 h）、7.5和5 mg/kg bw，连续1、3和7 d，观察小鼠行为学特征、中枢神经组织线粒体超微结构和功能变化，探讨硫酸粘杆菌素神经毒性的机制。为了评估粘菌素诱导的神经毒性的可恢复性，还在第15天（硫酸粘菌素施用7天后8天）检查神经毒性。结果表明，与相应对照组相比，15 mg/kg剂量组小鼠自发活动在第3天和第7天显著减少。神经组织线粒体超微结构出现异常变化，并呈剂量和时间依赖性，如15 mg/kg组第3天和第7天出现严重空泡化和分裂，7.5 mg/kg组第7天较轻。此外，黏菌素还可引起线粒体膜电位（Δ psi（m））、线粒体膜通透性转换（MPT）和线粒体琥珀酸脱氢酶（SDH）活性的变化，表明黏菌素影响线粒体功能。15 mg/kg组小鼠神经组织在第15天仅出现轻微损伤，而7.5和5 mg/kg组小鼠在第15天的行为学和神经病理学特征未见异常改变。结果提示，线粒体功能障碍可能是硫酸粘杆菌素神经毒性的部分机制。(C)2013年爱思唯尔有限公司。All rights reserved.
In the present study, the mechanism of colistin-induced neurotoxicity was investigated with a focus on behavioral characters, mitochondrial ultrastructures and functions of the central nerve tissues in mice followed by administrating intravenously 15 (divided into two dose and 12 h apart), 7.5 and 5 mg/kg bw colistin sulfate for 1, 3 or 7 days successively. To assess the recoverability of colistin-induced neurotoxicity, the neurotoxicity was also examined on day 15 (8 post colistin sulfate administration for 7 days). The results showed that, the spontaneous activities of mice were significantly decreased on days 3 and 7 in the 15 mg/kg group compared with the correspondingly control group. The abnormal ultrastructure changes of mitochondria were presented in their nervous tissues and changed in a dose- and time-dependent manner, e.g. severe vacuolation and fission on days 3 and 7 in the 15 mg/kg group and more slight on day 7 in the 7.5 mg/kg group. In addition, mitochondrial permeability transition (MPT), membrane potential (Delta psi(m)) and activities of mitochondrial succinate dehydrogenase changed, showing that colistin affected the mitochondrial functions. The recoverability of colistin-induced neurotoxicity was showed and only slight injury occurred in the nerve tissues of mice on day 15 in the 15 mg/kg group and it had no abnormal changes in the behavioral and neuropathology characters in mice on day 15 in the 7.5 and 5 mg/kg groups. The results suggested that mitochondrial dysfunction might partly account for the mechanism of neurotoxicity induced by colistin sulfate. (C) 2013 Elsevier GmbH. All rights reserved.