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Environ Sci Pollut Res Int. 2010 Jan;17(1):181-6. doi: 10.1007/s11356-009-0117-5. Epub 2009 Mar 10.
BACKGROUND, AIM, AND SCOPE: Hexanitrohexaazaisowurtzitane (CL-20) is a relatively new energetic compound sharing some degree of structural similarity with hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), a known neurotoxic compound. Previously, we demonstrated using a noninvasive electrophysiological technique that CL-20 was a more potent neurotoxicant than RDX to the earthworm Eisenia fetida. In the present study, we investigated the effect of CL-20 exposure and subsequent recovery on muscarinic acetylcholine receptors (mAChRs) to further define the mechanism of reversible neurotoxicity of CL-20 in E. fetida.
We used a noninvasive electrophysiological technique to evaluate neurotoxicity in CL-20-treated worms, and then measured how such exposures altered levels of whole-body mAChR in the same animals.
A good correlation exists between these two types of endpoints. Effect on mAChR levels was most prominent at day 6 of exposure. After 7 days of recovery, both conduction velocity and mAChR were significantly restored. Our results show that sublethal concentrations of CL-20 significantly reduced mAChR levels in a concentration- and duration-dependent manner, which was accompanied with significant decreases in the conduction velocity of the medial and lateral giant nerve fibers. After 7-day post exposure recovery, worms restored both neurochemical (mAChR) and neurophysiological (conduction velocity) endpoints that were reduced during 6-day exposures to CL-20 concentrations from 0.02 to 0.22 microg/cm(2).
Our findings support the idea that CL-20 induced neurotoxic effects are reversible, and suggest that CL-20 neurotoxicity may be mediated through the cholinergic system. Future studies will investigate other neurotransmission systems such as GABA, glutamate, and monoamine. Ion channels in the nerve membrane should be examined to further define the precise mechanisms underlying CL-20 neurotoxicity.
背景、目的和范围：六硝基六氮杂异伍兹烷（CL-20）是一种相对较新的高能化合物，在结构上与六氢-1,3,5-三硝基-1,3,5-三嗪（RDX）有一定程度的相似性，RDX 是一种已知的神经毒性化合物。此前，我们使用一种非侵入性的电生理学技术证明，CL-20 对蚯蚓 Eisenia fetida 的神经毒性强于 RDX。在本研究中，我们研究了 CL-20 暴露及其随后的恢复对毒蕈碱乙酰胆碱受体（mAChR）的影响，以进一步确定 CL-20 在 E. fetida 中可逆神经毒性的机制。
我们使用非侵入性的电生理学技术评估 CL-20 处理后的蠕虫的神经毒性，然后测量这种暴露如何改变同一动物体内的全身 mAChR 水平。
这两种终点之间存在良好的相关性。暴露第 6 天，mAChR 水平的变化最为显著。暴露后 7 天恢复时，传导速度和 mAChR 均显著恢复。我们的结果表明，亚致死浓度的 CL-20 以浓度和时间依赖的方式显著降低 mAChR 水平，同时显著降低中侧巨神经纤维的传导速度。暴露后 7 天恢复时，蠕虫恢复了暴露于 0.02 至 0.22 μg/cm(2) CL-20 浓度 6 天后降低的神经化学（mAChR）和神经生理（传导速度）终点。
我们的发现支持 CL-20 诱导的神经毒性作用是可逆的观点，并表明 CL-20 神经毒性可能通过胆碱能系统介导。未来的研究将调查其他神经递质系统，如 GABA、谷氨酸和单胺。应检查神经膜中的离子通道，以进一步确定 CL-20 神经毒性的确切机制。
