Bioscavenger is effective as a delayed therapeutic intervention following percutaneous VX poisoning in the guinea-pig
| Autor: | T.R. Laws, Charlotte Whitmore, E.R. Emery, Matthew E. Price, John E.H. Tattersall, R.L. Perrott, R.R. McColm, A.C. Green, Helen Rice, T.M. Mann |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Atropine Male Cholinesterase Reactivators Percutaneous Antidotes Guinea Pigs Pyridinium Compounds Muscarinic Antagonists Toxicology Administration Cutaneous Time-to-Treatment Guinea pig 03 medical and health sciences 0302 clinical medicine Oximes medicine Toxicokinetics Animals Cholinesterases Dosing Chemical Warfare Agents Butyrylcholinesterase Nerve agent business.industry Avizafone Organothiophosphorus Compounds General Medicine Dipeptides 030104 developmental biology 030220 oncology & carcinogenesis Anesthesia business Nerve Agents medicine.drug |
| Zdroj: | Toxicology letters. 293 |
| ISSN: | 1879-3169 |
| Popis: | The prolonged systemic exposure that follows skin contamination with low volatility nerve agents, such as VX, requires treatment to be given over a long time due to the relatively short half-lives of the therapeutic compounds used. Bioscavengers, such as butyrylcholinesterase (BChE), have been shown to provide effective post-exposure protection against percutaneous nerve agent when given immediately on signs of poisoning and to reduce reliance on additional treatments. In order to assess the benefits of administration of bioscavenger at later times, its effectiveness was assessed when administration was delayed for 2h after the appearance of signs of poisoning in guinea-pigs challenged with VX (4×LD50). VX-challenged animals received atropine, HI-6 and avizafone on signs of poisoning and 2h later the same combination with or without bioscavenger. Five out of 6 animals which received BChE 2h after the appearance of signs of poisoning survived to the end of the study at 48h, compared with 6 out of 6 which received BChE immediately on signs. All the animals (n=6+6) that received only MedCM, without the addition of BChE, died within 10h of poisoning. The toxicokinetics of a sub-lethal challenge of percutaneous VX were determined in untreated animals. Blood VX concentration peaked at approximately 4h after percutaneous dosing with 0.4×LD50; VX was still detectable at 36h and had declined to levels below the lower limit of quantification (10pg/mL) by 48h in 7 of 8 animals, with the remaining animal having a concentration of 12pg/mL. These studies confirm the persistent systemic exposure to nerve agent following percutaneous poisoning and demonstrate that bioscavenger can be an effective component of treatment even if its administration is delayed. |
| Databáze: | OpenAIRE |
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