کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
11030728 | 1646166 | 2018 | 35 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Superior efficacy of HI-6 dimethanesulfonate over pralidoxime methylsulfate against Russian VX poisoning in cynomolgus monkeys (Macaca fascicularis)
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کلمات کلیدی
LD50i.v.CHESOrganophosphorus - ارگانوفسفورAcetylcholinesterases - استیل کولین استرازIntravenous - داخل وریدیlethal dose 50% - دوز مرگبار 50٪Atropine sulfate - سولفات آتروپینNerve agent - عامل عصبIntramuscular - عضلانیOrganophosphorus nerve agents - عوامل عصبی ارگانوفسفورi.m. - من هستم.non-human primate - نخستیسانان غیرانسانیCholinesterases - کولین استراز
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم محیط زیست
بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Organophosphorus nerve agents still represent a serious risk to human health. In the French armed forces, the current emergency treatment against OP intoxications is a fully licensed wet-dry dual-chambered autoinjector (Ineurope ®), that contains pralidoxime methylsulfate (2-PAM) to reactivate inhibited acetylcholinesterase (AChE), atropine sulfate (AS) and avizafone chlorhydrate (AVZ). While this treatment is effective against several of the known nerve agents, it shows little efficacy against the Russian VX (VR), one of the most toxic compounds. HI-6 dimethanesulfonate (HI-6 DMS) is an oxime able to reactivate in vitro and in vivo VR-inhibited AChE. To confirm the superiority of HI-6 DMS towards 2-PAM prior to licensing, we compared the two 3-drug-combinations (HI-6 vs 2-PAM, 33 and 18âmg/kg respectively, equimolar doses; AS/AVZ 0.25/0.175âmg/kg respectively) in VR-poisoned cynomolgus macaques, the model required by the French drug regulatory agency. In parallel we performed HI-6 pharmacokinetics analysis using a one compartment model. A better efficacy of the HI-6 DMS combination was clearly observed: up to 5 LD50 of VR (i.m.), a single administration of the HI-6 DMS combination, shortly after the onset of clinical signs, prevented death of the four intoxicated animals. Conversely 2-PAM only prevented death in one out of three subjects exposed to the same amount of VR. As expected with V agents, reinhibition of blood AChE was observed but without any apparent impact on the clinical recovery of the animals. A single administration of the HI-6 DMS combination was still but partially effective at 15 LD50 of VR, allowing a 50% survival rate.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology - Volume 410, 1 December 2018, Pages 96-105
Journal: Toxicology - Volume 410, 1 December 2018, Pages 96-105
نویسندگان
Chloé Reymond, Nina Jaffré, Nicolas Taudon, Mathilde Menneteau, Hervé Chaussard, Josiane Denis, Cédric Castellarin, Franck Dhote, Frédéric Dorandeu,