Asoxime (HI-6) impact on dogs after one and tenfold therapeutic doses: assessment of adverse effects, distribution, and oxidative stress

Environ Toxicol Pharmacol. 2011 Jul;32(1):75-81. doi: 10.1016/j.etap.2011.03.014. Epub 2011 Apr 1.

Abstract

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.

MeSH terms

  • Acetylcholinesterase / metabolism
  • Animals
  • Blood Glucose / analysis
  • Blood Urea Nitrogen
  • Cholinesterase Reactivators / administration & dosage*
  • Cholinesterase Reactivators / blood
  • Cholinesterase Reactivators / pharmacokinetics
  • Creatine Kinase / blood
  • Dogs
  • Glutathione / blood
  • Glutathione Disulfide / blood
  • Hyperglycemia / blood
  • Hyperglycemia / chemically induced
  • Oxidative Stress*
  • Oximes / administration & dosage*
  • Oximes / blood
  • Oximes / pharmacokinetics
  • Pyridinium Compounds / administration & dosage*
  • Pyridinium Compounds / blood
  • Pyridinium Compounds / pharmacokinetics
  • Sulfhydryl Compounds / blood
  • Thiobarbituric Acid Reactive Substances / metabolism
  • Triglycerides / blood

Substances

  • Blood Glucose
  • Cholinesterase Reactivators
  • Oximes
  • Pyridinium Compounds
  • Sulfhydryl Compounds
  • Thiobarbituric Acid Reactive Substances
  • Triglycerides
  • Creatine Kinase
  • Acetylcholinesterase
  • Glutathione
  • asoxime chloride
  • Glutathione Disulfide