Neurochemical correlates of chlordecone neurotoxicity.

Neurochemical correlates of chlordecone neurotoxicity.
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十氯酮神经毒性的神经化学相关性。

DOI:
10.1080/15287398109530107
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发表时间:
1981
期刊:
Journal of toxicology and environmental health
影响因子:
--
通讯作者:
Dewey,WL
Dewey,WL
中科院分区:
--
文献类型:
--
作者:
End,DW;Carchman,RA;Dewey,WL

文献摘要

参考文献

被引文献

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研究人员在几种体外生物神经化学系统中检测了具有神经毒性的有机氯杀虫剂十氯酮(Kepone),试图确定可能与十氯酮毒性人类中枢神经系统表现相关的神经化学改变。在体外,十氯酮是脑线粒体氧化磷酸化和相关Ca2+运输的显著有效抑制剂(Ki= 10−7M)。在高浓度十氯酮(10−5M)下,观察到生物膜的不稳定。这两种作用似乎都有助于抑制突触体Ca2+摄取,这伴随着神经递质释放的明显刺激,尽管矛盾。对[14C]十氯酮处理的研究表明,在体外引起神经化学变化的浓度与在完整动物中以40 mg/kg致震颤剂量达到的脑组织十氯酮浓度相当。然而,在十氯酮中毒动物多巴胺和去甲肾上腺素转换的研究中,没有观察到十氯酮毒性的神经化学相关物质。这些发现讨论了神经化学分析的发展,适用于调查神经毒性毒剂。
The neurotoxic organochlorine insecticide chlordecone (Kepone) was examined in severalin vitroandin vivoneurochemical systems in an attempt to identify neuro‐chemical alterations that might be relevant to the central nervous system manifestations of chlordecone toxicity in humans.In vitro, chlordecone was a remarkably potent inhibitor of brain mitochondrial oxidative phosphorylation and associated Ca2+transport (Ki= 10−7M). At a high concentration of chlordecone (10−5M), destabilization of biological membranes was observed. Both of these effects appeared to contribute to inhibition of synaptosomal Ca2+uptake, which was accompanied by a pronounced, although paradoxical, stimulation of neurotransmitter release. Studies of the disposition of [14C]chlordecone revealed that the concentrations that elicited neurochemical changesin vitrowere comparable to the brain tissue chlordecone concentrations achieved with a 40 mg/kg tremorigenic dose in intact animals. However, no neurochemical correlates of chlordecone toxicity were observed in studies of dopamine and norepinephrine turnover in chlordecone‐intoxicated animals. These findings are discussed in relation to the development of neurochemical assays appropriate for investigating neurotoxic agents.
Kepone:文献摘要。
DOI: --
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期刊:
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