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Evaluation of reactivation test in anaesthetized dogs with experimental intoxication with nerve agents
J Bajgar1, J Fusek, L Bartosova
1Department of Toxicology, Faculty of Military Health Sciences, University of Defence, Trebesska 1575, 500 01 Hradec Kralove, Czech Republic.
Abstract:
Following repeated antidotal treatment of anaesthetized dogs (1 min with atropine, 10 min with atropine and obidoxime, 60 min with atropine and obidoxime) after the intoxication with soman, sarin and VX (1 x LD50, i.m.), the blood cholinesterases (erythrocyte, whole blood, plasma) were monitored and their reactivatability (whole blood) was determined. During this treatment, the activities of erythrocyte acetylcholinesterase (AChE), plasma butyrylcholinesterase (BuChE) and whole blood cholinesterases were monitored. Atropine and obidoxime did not affect cholinesterase activities in control animals, whereas administration of obidoxime to dogs intoxicated with nerve agent caused an increase in the cholinesterase activities. The sensitivity of cholinesterases decreased in the order erythrocyte AChE > whole blood cholinesterases > plasma BuChE, respectively. Following sarin intoxication, blood cholinesterases were increased after the obidoxime administration. Intoxication with VX showed a similar picture but reactivation after the obidoxime administration was greater. In soman intoxication, the picture of cholinesterase changes was similar during the first 30 min of treatment. Then the increase in AChE activity following obidoxime administration was not as high as in the case of sarin and VX intoxication. Thus, the reactivation efficacy of obidoxime during nerve agent intoxication indicates that its repeated administration could be easily monitored using the reactivation test.
Insights
Repeated administration of obidoxime increased cholinesterase activity in dogs intoxicated with nerve agents like soman, sarin, and VX. This reactivation can be monitored using a simple blood test, aiding in treatment efficacy assessment.
Area of Science:
- Toxicology
- Pharmacology
- Biochemistry
Background:
- Nerve agents like soman, sarin, and VX inhibit cholinesterases, critical enzymes for nerve function.
- Antidotal treatments involving atropine and obidoxime are used to counteract nerve agent toxicity.
- Monitoring the efficacy of antidotal treatments, particularly cholinesterase reactivation, is crucial for patient recovery.
Purpose of the Study:
- To evaluate the efficacy of repeated obidoxime administration in reactivating blood cholinesterases inhibited by soman, sarin, and VX.
- To compare the sensitivity of different blood cholinesterases (erythrocyte acetylcholinesterase, plasma butyrylcholinesterase, whole blood cholinesterases) to nerve agent intoxication and subsequent treatment.
- To determine if the reactivation test can be used to monitor the effectiveness of repeated obidoxime treatment.
Main Methods:
- Anesthetized dogs were intoxicated with soman, sarin, or VX (1 x LD50, i.m.).
- Dogs received repeated antidotal treatment: atropine alone initially, followed by atropine and obidoxime over 10 and 60 minutes.
- Blood cholinesterase activities (erythrocyte, whole blood, plasma) were monitored, and whole blood cholinesterase reactivatability was determined.
Main Results:
- Atropine and obidoxime did not affect cholinesterase activity in control animals.
- Obidoxime administration increased cholinesterase activity in nerve agent-intoxicated dogs.
- Cholinesterase sensitivity decreased in the order: erythrocyte AChE > whole blood cholinesterases > plasma BuChE.
- Reactivation efficacy varied by nerve agent, with VX showing greater reactivation than soman, and sarin also demonstrating significant increases in cholinesterase activity post-obidoxime.
Conclusions:
- Repeated obidoxime administration effectively reactivates blood cholinesterases inhibited by soman, sarin, and VX in dogs.
- The degree of cholinesterase reactivation varies depending on the specific nerve agent.
- The reactivation test provides a reliable method for monitoring the efficacy of repeated obidoxime administration during nerve agent intoxication.
