Effects of CBDP and MEPQ on the toxicity and distribution of [3H]-soman in mice.
Soman poisoning presents a problem in terms of its detailed pathophysiology and its detoxification mechanism(s). The present study was designed to evaluate the role of carboxylesterases (CaE) and cholinesterase (ChE) in the distribution and detoxification of soman in vivo. Mice were injected (i.v.) with 0.06-1.0 LD50 of [3H]-soman, 60 min following pretreatment with either 2-O-cresyl-4H-1:2:3 benzodioxa-phosphorine-2-oxide (CBDP), which blocks CaE or 7-(methylethoxyphosphinyloxy)-1-methyl quinolinium iodide (MEPQ), which selectively inhibits intravascular ChE. One hour after [3']-soman administration animals were sacrificed and whole body autoradiography was performed. High concentrations of [3H]-soman were found in lung and kidney in control mice, and low concentrations were found in central nervous system. Pretreatment with CBDP caused a 93% decrease in radioactive labelling in the lung, and a minor decrease in overall labelling, whereas pretreatment with MEPQ did not change the distribution pattern of [3H]-soman. It is concluded that lung is a major target organ for soman detoxification and that it exerts this effect by means of enzymatic reaction with soman through the abundant amounts of CaE which are present in the lung. Intravascular ChE has little (if any) effect on the distribution and detoxification of soman in vivo.
Shapira
S
S
Department of Pharmacology, Israel Institute for Biological Research, Ness-Ziona.
Kadar
T
T
Cohen
G
G
Chapman
S
S
Raveh
L
L
D000818:Animals; D002265:Carboxylic Ester Hydrolases / Q000037:antagonists & inhibitors*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D008168:Lung / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D011806:Quinolinium Compounds / Q000494:pharmacology*; D012999:Soman / Q000493:pharmacokinetics / Q000633:toxicity*; D014018:Tissue Distribution; D014316:Tritium
D002800:Cholinesterase Inhibitors; D009943:Organophosphorus Compounds; D011806:Quinolinium Compounds; D014316:Tritium; C000516:2-(2-cresyl)-4H-1-3-2-benzodioxaphosphorin-2-oxide; C044294:7-((methylethoxyphosphinyl)oxy)-1-methylquinolinium; D012999:Soman; D002265:Carboxylic Ester Hydrolases