MANGANESE-INDUCED REACTIVE OXYGEN SPECIES - COMPARISON BETWEEN MN+2 AND MN+3
MANGANESE-INDUCED REACTIVE OXYGEN SPECIES - COMPARISON BETWEEN MN+2 AND MN+3
复制标题
DOI：
10.1016/1055-8330(95)90023-3
复制
发表时间：
1995-09-01
期刊：
影响因子：
--
通讯作者：
SLIKKER, W
中科院分区：
文献类型：
--
作者：
ALI, SF;DUHART, HM;SLIKKER, W
锰（Mn）是一种必需元素，已知其缺乏或过量会导致实验动物和人的神经毒性。锰的神经毒性作用机制尚不清楚。本研究旨在评估体外或体内暴露于Mn是否会产生活性氧（ROS）。我们还试图确定单次注射锰是否会产生大鼠大脑不同区域单胺浓度的变化。成年Sprague-Dawley大鼠分别给药0、50或100 mg/kg，分别给药MnCl2 （Mn+2）或MnOAc (Mn+3)，给药1 h后处死。大脑被迅速移除并解剖以进行神经化学分析。用分子探针2′，7′-二氯荧光素二乙酸酯（DCFH-DA）测定活性氧，用HPLC/EC测定单胺及其代谢物。体外暴露于MnCl2 （1-1000 μ M）会导致纹状体中ROS的剂量依赖性增加，而低浓度（1-100 μ M）的MnOAc也会产生类似的增加。体内暴露于MnOAc （Mn+3）会导致尾状核和海马中ROS的显著增加，而MnCl2 （Mn+2）仅在海马中产生显著影响。急性注射MnCl2或MnOAc均未改变多巴胺、血清素及其代谢物（DOPAC、HVA和5-HIAA）的浓度。这些数据表明，二价和三价锰都能诱导ROS，但Mn+3比Mn+2更有效。1995学术出版社有限公司
Manganese (Mn) is an essential element, the deficiency or excess of which is known to cause neurotoxicity in experimental animals and man. The mechanism of action of Mn neurotoxicity is still unclear. The present study was designed to evaluate whether in vitro or in vivo exposure to Mn produced reactive oxygen species (ROS). We also sought to determine if a single injection of Mn produces changes in monoamines concentration in different regions of rat brain. Adult Sprague-Dawley rats were dosed with 0, 50 or 100 mg/kg, ip with either MnCl2 (Mn+2) or MnOAc (Mn+3) and were sacrificed 1 h after the dose was administered. Brains were quickly removed and dissected for neurochemical analysis. ROS were measured by a molecular probe, 2',7'-dichlorofluorescein diacetate (DCFH-DA), and monoamines and their metabolites were measured by HPLC/EC. In vitro exposure to MnCl2 (1-1000 mu M) produced dose-dependent increases of ROS in striatum whereas MnOAc produced similar increases at much lower concentrations (1-100 mu M) In vivo exposure to MnOAc (Mn+3) produced significant increases of ROS in caudate nucleus and hippocampus, whereas MnCl2 (Mn+2) produced significant effects only in hippocampus. Concentrations of dopamine, serotonin and their metabolites (DOPAC, HVA and 5-HIAA) were not altered with acute injections of either MnCl2 or MnOAc. These data suggest that both divalent and trivalent manganese induce ROS, however, Mn+3 is an order of magnitude more potent than Mn+2. (C) 1995 Academic Press Limited