Organophosphorus-induced delayed neuropathy: A simple and efficient therapeutic strategy
Organophosphorus-induced delayed neuropathy: A simple and efficient therapeutic strategy
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DOI：
10.1016/j.toxlet.2009.10.032
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发表时间：
2010-02-01
影响因子：
3.5
通讯作者：
de Oliveira, Georgino H.
中科院分区：
文献类型：
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作者：
Emerick, Guilherme L.;Peccinini, Rosangela G.;de Oliveira, Georgino H.
有机磷（OP）用作杀虫剂和液压液会产生急性中毒，称为OP引起的迟发性神经病（OPIDN），其影响需要很长时间才能恢复。因此，一种安全的治疗策略来预防这种中毒最严重的影响将受到欢迎。在这项研究中，给母鸡注射磷酸三邻甲苯酯（TOCP，500 mg/kg，口服），随后或不注射尼莫地平（1 mg/kg，肌肉注射）和葡萄糖酸钙（Ca-glu，5 mg/kg，静脉注射）。 TOCP中毒后6小时，观察到神经病靶酯酶(NTE)活性抑制，24小时后达到峰值，抑制超过80%。给予 TOCP 12 小时后，血浆钙水平下降，24 小时后，坐骨神经中的 Ca2+ 下降 56.4%；同时钙激活中性蛋白酶（CANP）活性增加308.7%，效果持续14天。任何在 TOCP 中毒后接受治疗的鸟类都表现出明显的 OPIDN 症状。这些结果表明，NTE 可能参与调节钙进入细胞，负责维持钙通道的正常功能，而增加 CANP 活性则负责触发 OPIDN。因此，通过适当调整尼莫地平和 Ca-glu 的剂量，我们相信这种治疗策略可用于患有神经性 OP 急性中毒的人类。 (C) 2009 Elsevier Ireland Ltd. 保留所有权利。
Organophosphorus (OP) used as pesticides and hydraulic fluids can produce acute poisoning known as OP-induced delayed neuropathy (OPIDN), whose effects take long time to recover. Thus a secure therapeutic strategy to prevent the most serious effects of this poisoning would be welcome. In this study, tri-o-cresyl phosphate (TOCP, 500 mg/kg p.o.) was given to hens, followed or not by nimodipine (1 mg/kg i.m.) and calcium gluconate (Ca-glu 5 mg/kg i.v.). Six hours after TOCP intoxication, neuropathy target esterase (NTE) activity inhibition was observed, peaking after 24 It exceeding 80% inhibition. A fall in the plasmatic calcium levels was noted 12 h after TOCP was given and, in the sciatic nerve, Ca2+ fell 56.4% 24 h later; at the same time calcium activated neutral protease (CANP) activity increased 308.7%, an effect that lasted 14 days. Any bird that received therapeutic treatment after TOCP intoxication presented significant signs of OPIDN. These results suggest that NTE may be implicated in the regulation of calcium entrance into cells being responsible for the maintenance of normal function of calcium channels, and that increasing CANP activity is responsible to triggering OPIDN. Thus, with one suitably adjusted dose of nimodipine as well as Ca-glu, we believe that this treatment strategy may be used in humans with acute poisoning by neuropathic OP. (C) 2009 Elsevier Ireland Ltd. All rights reserved.