ORGANOMETAL-INDUCED INCREASES IN OXYGEN REACTIVE SPECIES - THE POTENTIAL OF 2',7'-DICHLOROFLUORESCIN DIACETATE AS AN INDEX OF NEUROTOXIC DAMAGE
ORGANOMETAL-INDUCED INCREASES IN OXYGEN REACTIVE SPECIES - THE POTENTIAL OF 2',7'-DICHLOROFLUORESCIN DIACETATE AS AN INDEX OF NEUROTOXIC DAMAGE
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DOI：
10.1016/0041-008x(90)90278-3
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发表时间：
1990-06-01
影响因子：
3.8
通讯作者：
BONDY, SC
中科院分区：
文献类型：
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作者：
LEBEL, CP;ALI, SF;BONDY, SC
用2‘’，7‘-二氯二乙酸二氯荧光素(DCFH-DA)为探针，用荧光指示剂Fluo-3研究了神经毒性金属甲基汞(MeHg)和三甲基锡(TMT)对突触体粗提物(P2)和细胞内钙([Ca+]i)形成的影响。单次注射甲基汞(1 mg/kg)后2天和7天，小脑氧活性物质的形成率明显增加。注射TMT(3 mg/kg)后2天，大鼠海马区和额叶皮质氧反应性明显升高。体外暴露于甲基汞(10-20微米)可增加氧活性物质的形成速率，而TMT(5-40微米)则无此作用。用任何一种有机金属处理的动物的小脑和海马体的P2组分中的[Ca~(2+)]i水平没有改变。数据表明，大脑区域、小脑(MeHg)和海马区(TMT)的氧反应物种增加，据信这些有毒物质选择性地容易受到这些毒物的影响。研究结果表明，氧化损伤可能是这两种有机金属毒性的一个机制。DCFH-DA的使用可能在神经系统中作为神经毒性损伤的指示器。
The effects of the neurotoxic metals methylmercury (MeHg) and trimethyltin (TMT) on oxygen reactive species formation within a crude synaptosomal fraction (P2), using the probe 2'',7''-dichlorofluorescin diacetate (DCFH-DA), and intracellular calcium ([Ca2+]i), with the fluorescent indicator fluo-3, have been investigated. Two and seven days after a single injection of MeHg (1 mg/kg) the formation rate of cerebellar oxygen reactive species was significantly increased. Hippocampal and frontocortical oxygen reactive species were elevated 2 days after TMT injection (3 mg/kg). In vitro exposure to MeHg (10-20.mu.M) increased the formation rate of oxygen reactive species, while TMT (5-40 .mu.M) was without effect. Levels of [Ca2+]i were unaltered in P2 fractions from cerebellum and hippocampus of animals treated with either organometal. The data demonstrate that oxygen reactive species are elevated in brain regions, cerebellum (MeHg) and hippocampus (TMT), believed to be selectively vulnerable to these toxic agents. Findings suggest that oxidative damage may be a mechanism underlying the toxicity of both organometals. The use of DCFH-DA may have potential in the nervous system as an indicator of neurotoxic damage.