Abstract
1. To study the influence of pharmacological pretreatment (PANPAL or pyridostigmine combined with biperiden) and antidotal treatment (the oxime HI-6 plus atropine) on soman-induced neurotoxicity, male albino rats were poisoned with a lethal dose of soman (54 (g/kg i.m.; 100% of LD50 value) and observed at 24 hours and 7 days following soman challenge. The neurotoxicity of soman was evaluated using a Functional observational battery and an automatic measurement of motor activity. 2. Pharmacological pretreatment as well as antidotal treatment were able to eliminate some of soman-induced neurotoxic effects observed at 24 hours following soman poisoning. The combination of pharmacological pretreatment (PANPAL or pyridostigmine combined with biperiden) and antidotal treatment was found to be more effective in the elimination of soman-induced neurotoxicity in rats at 24 hours following soman challenge in comparison with the administration of pharmacological pretreatment or antidotal treatment alone. To compare both pharmacological pretreatments, the combination of pyridostigmine with biperiden seems to be more efficacious to eliminate soman-induced signs of neurotoxicity than PANPAL. 3. At 7 days following soman poisoning, the combination of pharmacological pretreatment involving pyridostigmine and biperiden with antidotal treatment was only able to completely eliminate soman-induced neurotoxic signs. 4. Thus, our findings confirm that the combination of pharmacological pretreatment and antidotal treatment is able not only to protect the experimental animals from the lethal effects of soman but also to eliminate most soman-induced signs of neurotoxicity in poisoned rats. The pharmacological pretreatment containing pyridostigmine and biperiden appears to be more efficacious to eliminate soman-induced neurotoxic sings than PANPAL.
Highlights
Despite of the entry into force in April 1997 of the Chemical Weapons Convention forbidding the production, storage and use of chemical warfare agents, the world has seen a rapid proliferation of such agents, especially nerve agents
Pharmacological pretreatment as well as antidotal treatment were able to eliminate some of soman-induced neurotoxic effects observed at 24 hours following soman poisoning
The combination of pharmacological pretreatment (PANPAL or pyridostigmine combined with biperiden) and antidotal treatment was found to be more effective in the elimination of soman-induced neurotoxicity in rats at 24 hours following soman challenge in comparison with the administration of pharmacological pretreatment or antidotal treatment alone
Summary
Despite of the entry into force in April 1997 of the Chemical Weapons Convention forbidding the production, storage and use of chemical warfare agents, the world has seen a rapid proliferation of such agents, especially nerve agents. The international control of their proliferation is thwarted by the ease of their synthesis and by similarity between their chemical precursors and widely used pest-control agents. Their harmful effect is related to their potency to irreversibly inhibit mammalian acetylcholinesterase (AChE, EC 3.1.1.7), the enzyme responsible for the regulation of neurotransmitter acetylcholine (ACh) concentration at cholinergic synapses [23]. The inhibition of AChE induces a major increase in ACh level in the cholinergic nervous system producing muscle fasciculations, respiratory distress and epileptic fits leading to the generalized seizures. The seizures lead to severe incapacitation and to irreversible brain damage with lesions especially in hippocampus, piriform cortex [17,21] and other cortical structures [13]
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