title: Biochemical insight into soman intoxication and treatment with atropine, HI-6, trimedoxime, and K203 in a rat model.
abstract: OBJECTIVE
  The present experiment is based on biochemical assessment of nerve agent soman intoxication and atropine, respectively atropine and HI-6, trimedoxime or K203 treatment in rats.
  
  
  BACKGROUND
  Nerve agents are toxic substances irreversibly inhibiting enzyme acetylcholinesterase (AChE). Treatment is typically based on application of atropine and oxime reactivator. Atropine is able to protect overstimulation of muscarinic acetylcholine receptors. Application of oxime reactivator enable return of AChE activity and full suppression of intoxication.
  
  
  METHODS
  In a total, fifteen biochemical markers were assayed in plasma or blood of intoxicated animals. 42 rats were divided into 7 groups each 6 individuals. The first group was exposed to atropine; the second group was exposed to one LD50 of soman and atropine. The groups 3-5 were exposed in a same way as the second group and were treated with oxime reactivators: HI-6 (group 3), trimedoxime (4) and K203 (5). The sixth group was control treated with saline solution only. The last (seventh) group was intoxicated with soman only.
  
  
  RESULTS
  The most striking shifts were found for blood acetylcholinesterase and plasma creatinine, glucose, inorganic phosphate as well as uric acid. Lactate dehydrogenase and aspartate aminotransferase assays were useless due to soman interference.
  
  
  CONCLUSIONS
  It was demonstrated that treatment was able to protect poisoned animals from metabolic disorder represented by hyperglycemia and nephropathy represented by hyperuricemia and elevated creatinine. Soman exposure and treatment with the oxime reactivators and/or atropine contains quite complex and still not well understood side mechanisms (Tab. 2, Fig. 1, Ref. 25).
authors.affiliation: Faculty of Military Health Sciences, University of Defense, Hradec Kralove, Czech Republic. miroslav.pohanka@gmail.com
authors.forename: M
authors.initials: M
authors.lastname: Pohanka
authors.forename: J
authors.initials: J
authors.lastname: Pikula
authors.forename: K
authors.initials: K
authors.lastname: Kuca
authors.forename: J
authors.initials: J
authors.lastname: Kassa
mesh_terms: D000818:Animals; D000931:Antidotes / Q000627:therapeutic use*; D001285:Atropine / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D002619:Chemical Warfare Agents / Q000506:poisoning*; D002800:Cholinesterase Inhibitors / Q000506:poisoning*; D002801:Cholinesterase Reactivators / Q000627:therapeutic use*; D008297:Male; D010091:Oximes / Q000627:therapeutic use; D011726:Pyridinium Compounds / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D012999:Soman / Q000506:poisoning*; D014289:Trimedoxime / Q000627:therapeutic use
chemical_list: C524716:1-(4-carbamoylpyridinium)-4-(4-hydroxyiminomethylpyridinium)but-2-ene; D000931:Antidotes; D015415:Biomarkers; D002619:Chemical Warfare Agents; D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D010091:Oximes; D011726:Pyridinium Compounds; D014289:Trimedoxime; D001285:Atropine; D012999:Soman; C022870:asoxime chloride