Effect of five acetylcholinesterase reactivators on tabun-intoxicated rats: induction of oxidative stress versus reactivation efficacy
Language English Country England, Great Britain Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
19338015
DOI
10.1002/jat.1432
Knihovny.cz E-resources
- MeSH
- Acetylcholinesterase blood metabolism MeSH
- Antidotes administration & dosage chemistry therapeutic use MeSH
- Atropine administration & dosage chemistry therapeutic use MeSH
- Cholinesterase Inhibitors administration & dosage chemistry toxicity MeSH
- Injections, Intramuscular MeSH
- Drug Therapy, Combination MeSH
- Rats MeSH
- Lethal Dose 50 MeSH
- Molecular Structure MeSH
- Molecular Weight MeSH
- Brain metabolism MeSH
- Obidoxime Chloride administration & dosage chemistry therapeutic use MeSH
- Organophosphates administration & dosage chemistry toxicity MeSH
- Oxidative Stress drug effects MeSH
- Rats, Wistar MeSH
- Pyridinium Compounds administration & dosage chemistry therapeutic use MeSH
- Cholinesterase Reactivators chemistry pharmacology MeSH
- Toxicity Tests, Acute MeSH
- Trimedoxime administration & dosage chemistry therapeutic use MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Acetylcholinesterase MeSH
- Antidotes MeSH
- Atropine MeSH
- Cholinesterase Inhibitors MeSH
- Obidoxime Chloride MeSH
- Organophosphates MeSH
- Pyridinium Compounds MeSH
- Cholinesterase Reactivators MeSH
- tabun MeSH Browser
- Trimedoxime MeSH
Oxime reactivators HI-6, obidoxime, trimedoxime, K347 and K628 were investigated as drugs designed for treatment of tabun intoxication. The experiments were performed on rats in order to simulate real conditions. Rats were intoxicated with one LD(50 )of tabun and treated with atropine and mentioned reactivators. Activities of erythrocyte acetylcholinesterase (AChE), plasma butyrylcholinesterase (BChE) and brain AChE were measured as markers of reactivation efficacy. An estimation of low molecular weight antioxidant levels using cyclic voltammetry was the second examination parameter. The evaluation of cholinesterases activity showed good reactivation potency of blood AChE and plasma BChE by commercially available obidoxime and newly synthesized K347. The potency of oximes to reactivate brain AChE was lower due to the poor blood-brain barrier penetration of used compounds. Commercially available reactivator HI-6 and newly synthesized K628 caused oxidative stress measured by cyclic voltammetry as antioxidant level. The oxidative stress provoked by HI-6 and K628 was found to be significant on probability level P = 0.05. The others reactivators did not affect antioxidant levels.
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