Asoxime (HI-6) is a well known oxime reactivator used for counteracting intoxication by nerve agents. It is able to reactivate acetylcholinesterase (AChE) inhibited even by sarin or soman. The present experiment was aimed to determine markers of oxidative stress represented by thiobarbituric acid reactive substances and antioxidants represented by ferric reducing antioxidant power, reduced and oxidized glutathione in a Beagle dog model. Two groups of dogs were intramuscularly exposed to single (11.4 mg/kg.b.wt.) or tenfold (114 mg/kg.b.wt.) human therapeutically doses of HI-6. HI-6 affinity for AChE in vitro was evaluated in a separate experiment. Complete serum biochemistry and pharmacokinetics were also performed with significant alteration in blood urea nitrogen, creatine phosphokinase, glucose and triglycerides. Blood samples were collected before HI-6 application and after 30, 60, and 120 min. The overall HI-6 impact on organism is discussed.
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http://dx.doi.org/10.1016/j.etap.2011.03.014 | DOI Listing |
Exp Neurol
December 2024
Neuroscience Department, U.S. Army Medical Research Institute of Chemical Defense (USAMRICD), Aberdeen Proving Ground, MD, United States of America. Electronic address:
Exposure to organophosphorus nerve agents irreversibly inhibits acetylcholinesterase and may lead to cholinergic crisis and seizures. Although benzodiazepines are the standard of care after nerve agent-induced status epilepticus, when treatment is delayed for up to 30 min or more, refractory status epilepticus can develop. Adult male rodents are often utilized for evaluation of therapeutic efficacy against nerve agent exposure.
View Article and Find Full Text PDFBioorg Chem
December 2024
University of Hradec Kralove, Faculty of Science, Department of Chemistry, Rokitanskeho 62, 500 03 Hradec Kralove, Czech Republic; University Hospital in Hradec Kralove, Biomedical Research Centre, Sokolska 581, 500 05 Hradec Kralove, Czech Republic. Electronic address:
Mono-quaternary pyridinium oximes derived from K-oximes K027, K048 and K203 were designed, synthesized and evaluated for the reactivation of organophosphate-inhibited cholinesterases. The incorporation of the halogen atoms to the structure decreased the pK value of the oxime group resulting in an increased formation of oximate necessary for reactivation. The stability and pK values were found to be similar to analogous bis-quaternary compounds.
View Article and Find Full Text PDFNeurotox Res
September 2024
Neuroscience Department, Medical Toxicology Research Division, U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD, 21010-5400, USA.
Recently a novel genetically modified mouse strain with serum carboxylesterase knocked-out and the human acetylcholinesterase gene knocked-in (KIKO) was created to simulate human responses to nerve agent (NA) exposure and its standard medical treatment. A adenosine receptor (AAR) agonist N-bicyclo-(2.2.
View Article and Find Full Text PDFNeuropharmacology
August 2024
Neuroscience Department, Medical Toxicology Research Division, U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD, 21010-5400, USA. Electronic address:
Organophosphorus nerve agents, such as soman (GD), produce excitotoxic effects resulting in sustained status epilepticus (SSE) and brain damage. Previous work shows that neuronal inhibitory effects of A adenosine receptor (AAR) agonists, such as N- Bicyclo (2.2.
View Article and Find Full Text PDFArch Toxicol
April 2024
University of Defence, Military Faculty of Medicine, Department of Toxicology and Military Pharmacy, Trebesska 1575, 500 01, Hradec Králové, Czech Republic.
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