...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of applied toxicology >Minireview: does in-vitro testing of oximes help predict their in-vivo action after paraoxon exposure?
【24h】

Minireview: does in-vitro testing of oximes help predict their in-vivo action after paraoxon exposure?

机译：Minireview：肟的体外测试是否有助于预测对氧磷暴露后的体内作用？

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

K-oximes have recently been developed in the search for efficacious broad-band reactivators of acetylcholinesterase (AChE) inhibited by organophosphorus compounds (OPC). Before clinical use, their toxicity and efficacy need to be assessed, and there is clear demand for simple in vitro tests that can predict in vivo performance. This article summarizes our in vitro data obtained for conventional and experimental oximes in human and rat blood exposed to the OPC paraoxon and correlates them with our in vivo results. The intrinsic AChE inhibitory activity of oximes, as reflected by their in vitro IC(50), is strongly correlated with their LD(50) (rat): oximes with a high IC(50) (K-27, K-48, pralidoxime and obidoxime) also show a high LD(50) and are thus relatively non-toxic, whereas oximes K-105, K-108 and K-113 have a low IC(50), a low LD(50) and are far more toxic. The IC(50) is also correlated with the in vivo capacity to protect from paraoxon-induced mortality: oximes with a higher IC(50) reduce the relative risk of death more. In contrast, the protective ability as assessed in vitro by the slope of the IC(50) shift (tanalpha), is not correlated with in vivo protection from paraoxon-induced mortality: the best in vivo protectors (K-27 and K-48) show a much lower tanalpha value (around 2) than K-110 and K-113 (tanalpha around 10), which hardly reduce the relative risk of death after paraoxon exposure. The partition coefficient logP of the individual oximes is inversely correlated with their IC(50) and with their LD(50) and is therefore an indicator of toxicity: strongly hydrophilic oximes tend to be less toxic than less hydrophilic ones. These data highlight the good predictive value of in vitro IC(50) testing for in vivo toxicity and the limited practical significance of in vitro assessment of protective potency.
机译：最近已开发了K-肟，以寻找有效的有机磷化合物（OPC）抑制的乙酰胆碱酯酶（AChE）宽带活化剂。在临床使用之前，需要评估它们的毒性和功效，并且明确需要可以预测体内性能的简单体外试验。本文总结了我们从暴露于OPC对氧磷的人和大鼠血液中常规和实验肟获得的体外数据，并将它们与我们的体内结果相关联。肟的内在AChE抑制活性由其体外IC（50）反映出，与它们的LD（50）（大鼠）密切相关：具有高IC（50）的肟（K-27，K-48，普利肟和obidoxime）也显示出高LD（50），因此相对无毒，而肟K-105，K-108和K-113的IC（50）较低，LD（50）较低，并且毒得多。有毒的。 IC（50）也与体内保护免受对氧磷所致死亡率的能力有关：具有较高IC（50）的肟可降低更多的相对死亡风险。相比之下，通过IC（50）位移的斜率（tanalpha）在体外评估的保护能力与体内免受对氧磷引起的死亡率的保护作用无关：最佳的体内保护剂（K-27和K-48 ）的tanalpha值（约2）比K-​​110和K-113（约10的tanalpha）低得多，这几乎不会降低对氧磷暴露后的相对死亡风险。各个肟的分配系数logP与它们的IC（50）和其LD（50）成反比，因此是毒性的指标：强亲水性肟的毒性比亲水性较低的肟低。这些数据凸显了体外IC（50）测试对体内毒性的良好预测价值，以及体外评估保护效能的有限的实际意义。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号