Tenocyclidine treatment in soman-poisoned rats--intriguing results on genotoxicity versus protection.
نویسندگان
چکیده
This study aimed to evaluate the antidotal potency of tenocyclidine (TCP) that probably might protect acetylcholinesterase (AChE) in the case of organophosphate poisoning. TCP was tested alone as a pretreatment or in combination with atropine as a therapy in rats poisoned with (1/4) and (1/2) of LD(50) of soman. Possible genotoxic effects of TCP in white blood cells and brain tissue were also studied. Results were compared with previous findings on the adamantyl tenocyclidine derivative TAMORF. TCP given alone as pretreatment, 5 min before soman, seems to be superior in the protection of cholinesterase (ChE) catalytic activity in the plasma than in brain, especially after administration of the lower dose of soman. Plasma activities of the enzyme after a joint treatment with TCP and soman were significantly increased at 30 min (P<0.001) and 24 h (P=0.0043), as compared to soman alone. TCP and atropine, given as therapy, were more effective than TCP administered alone as a pretreatment. The above therapy significantly increased activities of the enzyme at 30 min (P=0.046) and 24 h (P<0.001), as compared to controls treated with (1/4) LD(50) of soman alone. Using the alkaline comet assay, acceptable genotoxicity of TCP was observed. However, the controversial role of TCP in brain protection of soman-poisoned rats should be studied further.
منابع مشابه
A comparison of protective and anticonvulsive efficacy of two prophylactic mixtures in soman-poisoned rats
The protective and anticonvulsive efficacy of two prophylactic mixtures (PANPAL consisting of pyridostigmine, benactyzine, and trihexyphenidyle and pyridostigmine plus biperiden) administered prior to the administration of soman in a lethal dose (1.5 LD50) with or without antidotal treatment (atropine + HI-6) was evaluated using rats as experimental animals. The pretreatment was applied 30 and ...
متن کاملThe Evaluation of Benefit of Newly Prepared Reversible Inhibitors of Acetylcholinesterase and Commonly Used Pyridostigmine as Pharmacological Pretreatment of Soman-Poisoned Mice.
AIM The ability of four newly prepared reversible inhibitors of acetylcholinesterase (6-chlorotacrine, 7-phenoxytacrine, compounds 1 and 2) and currently used carbamate pyridostigmine to increase the resistance of mice against soman and the efficacy of antidotal treatment of soman-poisoned mice was evaluated. METHODS The evaluation of the effect of pharmacological pretreatment is based on the...
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Nerve agents are highly toxic organophosphorus (OP) compounds. They inhibit acetylcholinesterase (AChE), an enzyme that hydrolyses acetycholine (ACh) in the nervous system. Pathophysiological changes caused by OP poisonings are primarily the consequence of surplus ACh on cholinergic receptors and in the central nervous system. Standard treatment of OP poisoning includes combined administration ...
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The potency of the Czech original pharmacological pretreatment consisting of pyridostigmine, benactyzine and trihexyphenidyle, designated PANPAL, to increase the resistance of rats and mice against tabun or soman and to increase the therapeutic efficacy of standard antidotal treatment of tabun or soman-poisoned experimental animals was studied and compared with commonly used pyridostigmine alon...
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ورودعنوان ژورنال:
- Acta biochimica Polonica
دوره 55 1 شماره
صفحات -
تاریخ انتشار 2008