Tenocyclidine treatment in soman-poisoned rats--intriguing results on genotoxicity versus protection.
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.
Petek
Maja Jelena
MJ
Forensic Centre Ivan Vucetić, Ministry of Interior, Zagreb, Croatia.
Berend
Suzana
S
Kopjar
Nevenka
N
Zeljezić
Davor
D
Mladinić
Marin
M
Radić
Bozica
B
Vrdoljak
Ana Lucić
AL
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D002801:Cholinesterase Reactivators / Q000378:metabolism; D002802:Cholinesterases / Q000378:metabolism; D020552:Comet Assay; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D008956:Models, Chemical; D009153:Mutagens / Q000494:pharmacology; D010622:Phencyclidine / Q000031:analogs & derivatives; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012999:Soman / Q000506:poisoning*; D013876:Thiophenes / Q000494:pharmacology*
D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D009153:Mutagens; D010880:Piperidines; D013876:Thiophenes; C012058:tenocyclidine; D012999:Soman; D000110:Acetylcholinesterase; D002802:Cholinesterases; D010622:Phencyclidine