| Title: | 'Catch-up' therapy: combining antidotal treatment with dermal application of AHA following percutaneous VX poisoning in the domestic swine |
| Author(s): | Bloch-Shilderman E; Nili U; Nahum V; Smolkin B; Ashkenazi N; |
| Address: | "Department of Pharmacology, IIBR-Israel Institute for Biological Research, P.O. Box 19, 7410001, Ness Ziona, Israel. eugenias@iibr.gov.il. Department of Pharmacology, IIBR-Israel Institute for Biological Research, P.O. Box 19, 7410001, Ness Ziona, Israel. Department of Organic Chemistry, IIBR-Israel Institute for Biological Research, P.O. Box 19, 7410001, Ness Ziona, Israel. Department of Organic Chemistry, IIBR-Israel Institute for Biological Research, P.O. Box 19, 7410001, Ness Ziona, Israel. nissan.ashkenazi@iibr.gov.il. Department of Chemical Sciences, Ariel University, 4070000, Ariel, Israel. nissan.ashkenazi@iibr.gov.il" |
| DOI: | 10.1007/s00204-023-03574-5 |
| ISSN/ISBN: | 1432-0738 (Electronic) 0340-5761 (Linking) |
| Abstract: | "Low-volatility organophosphorus chemical warfare agents (OP CWAs) are cholinesterase inhibitors which easily absorb into the skin, leading to the formation of a dermal depot from which they slowly enter the bloodstream. This leads to sustained cholinergic hyperstimulation, which if untreated may lead to death. However, current available countermeasures are not adequate to neutralize the agent residing in the dermal depot. Accordingly, we evaluated the efficacy of the potassium salt of acetohydroxamic acid (880 mg/ml in DMSO/H(2)O 1:4, AHAK), as a potential 'catch-up' therapy lotion intended to neutralize the dermal depot, by penetrating the skin and decomposing it before it reaches the bloodstream. To that end, we compared the clinical outcome following skin surface decontamination combined with antidotal treatment, to that following the same antidotal treatment combined with dermal application of AHAK at the site of VX exposure, against percutaneous poisoning by a lethal neat dose (4 mg/kg) of the low-volatility nerve agent VX, in an unanesthetized swine model. Following skin surface decontamination and antidotal treatment, recurrence of intoxication signs and a prolonged recovery time were observed. In contrast, similar antidotal treatment combined with dermal application of AHAK significantly reduced intoxication signs recurrences and accordingly medical supervision duration needed, paralleled by a significantly faster recovery of whole blood cholinesterase activity. An initial evaluation demonstrated the safety of prolonged whole-body AHAK application. Hence, the AHAK lotion may act as an efficient 'catch-up' therapy against percutaneous poisoning by low-volatility OP CWAs, improving the clinical outcome and reducing the burden on medical staff" |
| Keywords: | Animals Swine Antidotes/therapeutic use *Organothiophosphorus Compounds/toxicity Cholinesterase Inhibitors *Chemical Warfare Agents Ahak Acetohydroxamic acid (AHA) Dermal depot Low-volatility OP CWAs Percutaneous poisoning/exposure Vx 'Catch-up' therapy; |
| Notes: | "MedlineBloch-Shilderman, Eugenia Nili, Uri Nahum, Victoria Smolkin, Boris Ashkenazi, Nissan eng Germany 2023/08/23 Arch Toxicol. 2023 Oct; 97(10):2771-2783. doi: 10.1007/s00204-023-03574-5. Epub 2023 Aug 23" |
