title: Asoxime (HI-6) impact on dogs after one and tenfold therapeutic doses: assessment of adverse effects, distribution, and oxidative stress.
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.
authors.affiliation: Faculty of Military Health Sciences, University of Defence, Trebesska 1575, 500 01 Hradec Kralove, Czech Republic. miroslav.pohanka@gmail.com
authors.forename: Miroslav
authors.initials: M
authors.lastname: Pohanka
authors.forename: Ladislav
authors.initials: L
authors.lastname: Novotny
authors.forename: Jana
authors.initials: J
authors.lastname: Zdarova-Karasova
authors.forename: Hana
authors.initials: H
authors.lastname: Bandouchova
authors.forename: Filip
authors.initials: F
authors.lastname: Zemek
authors.forename: Martina
authors.initials: M
authors.lastname: Hrabinova
authors.forename: Jan
authors.initials: J
authors.lastname: Misik
authors.forename: Kamil
authors.initials: K
authors.lastname: Kuca
authors.forename: Jiri
authors.initials: J
authors.lastname: Bajgar
authors.forename: Ondrej
authors.initials: O
authors.lastname: Zitka
authors.forename: Natalia
authors.initials: N
authors.lastname: Cernei
authors.forename: Rene
authors.initials: R
authors.lastname: Kizek
authors.forename: Jiri
authors.initials: J
authors.lastname: Pikula
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001806:Blood Urea Nitrogen; D002801:Cholinesterase Reactivators / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D003402:Creatine Kinase / Q000097:blood; D004285:Dogs; D005978:Glutathione / Q000097:blood; D019803:Glutathione Disulfide / Q000097:blood; D006943:Hyperglycemia / Q000097:blood / Q000139:chemically induced; D018384:Oxidative Stress; D010091:Oximes / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D011726:Pyridinium Compounds / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D013438:Sulfhydryl Compounds / Q000097:blood; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014280:Triglycerides / Q000097:blood
chemical_list: D001786:Blood Glucose; D002801:Cholinesterase Reactivators; D010091:Oximes; D011726:Pyridinium Compounds; D013438:Sulfhydryl Compounds; D017392:Thiobarbituric Acid Reactive Substances; D014280:Triglycerides; D003402:Creatine Kinase; D000110:Acetylcholinesterase; D005978:Glutathione; C022870:asoxime chloride; D019803:Glutathione Disulfide