新型肟类化合物逆转低剂量敌百虫诱导的大鼠通气效应的安全性和有效性。
Safety and Efficacy of New Oximes to Reverse Low Dose Diethyl-Paraoxon-Induced Ventilatory Effects in Rats.
机构信息
Bioactive Molecules Research Laboratory, Faculty of Sciences, Section II, Lebanese University, Beirut, Lebanon.
Laboratoire de Toxicologie Biologique, GH Lariboisière-St Louis-F. Widal, Assistance Publique-Hôpitaux de Paris (AP-HP), 75010 Paris, France.
出版信息
Molecules. 2020 Jul 3;25(13):3056. doi: 10.3390/molecules25133056.
BACKGROUND
Oximes are used in addition to atropine to treat organophosphate poisoning. However, the efficiency of oximes is still a matter of debate. In vitro experiments suggested than new oximes are more potent than the commercial oximes. However, the antidotal activity of new oximes has not been assessed in vivo.
METHODS
The aim of this work was to assess the safety and efficiency of new oximes compared to pralidoxime in a rat model of diethyl paraoxon-induced non-lethal respiratory toxicity.
RESULTS
Safety study of oximes showed no adverse effects on ventilation in rats. KO-33, KO-48, KO-74 oximes did not exhibit significant antidotal effect in vivo. In contrast, KO-27 and BI-6 showed evidence of antidotal activity by normalization of respiratory frequency and respiratory times. KO-27 became inefficient only during the last 30 min of the study. In contrast, pralidoxime demonstrated to be inefficient at 30 min post injection. Inversely, the antidotal activity of BI-6 occurred lately, within the last 90 min post injection.
CONCLUSION
This study showed respiratory safety of new oximes. Regarding, the efficiency, KO-27 revealed to be a rapid acting antidote toward diethylparaoxon-induced respiratory toxicity, meanwhile BI-6 was a late-acting antidote. Simultaneous administration of these two oximes might result in a complete and prolonged antidotal efficiency.
背景
肟类化合物被用于治疗有机磷中毒，与阿托品联合使用。然而，肟类化合物的疗效仍存在争议。体外实验表明，新型肟类化合物比商业肟类化合物更有效。然而，新肟类化合物的解毒活性尚未在体内进行评估。
方法
本研究旨在评估新肟类化合物与氯解磷定在大鼠二乙基对氧磷诱导的非致死性呼吸毒性模型中的安全性和疗效。
结果
肟类化合物的安全性研究表明，它们对大鼠的通气没有不良影响。KO-33、KO-48、KO-74 肟类化合物在体内没有表现出明显的解毒作用。相比之下，KO-27 和 BI-6 表现出了通过使呼吸频率和呼吸时间正常化来解毒的作用。KO-27 在研究的最后 30 分钟变得无效。相比之下，氯解磷定在注射后 30 分钟表现出无效。相反，BI-6 的解毒作用发生在最后 90 分钟内。
结论
本研究显示了新型肟类化合物的呼吸安全性。就疗效而言，KO-27 对二乙基对氧磷引起的呼吸毒性具有快速作用的解毒作用，而 BI-6 则是一种迟效解毒剂。这两种肟类化合物的同时给药可能会产生完全和持久的解毒效果。
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