Importance of aliesterase as a detoxification mechanism for soman (Pinacolyl methylphosphonofluoridate) in mice.
CBDP (2-/O-cresyl/4H:1:2-benzodioxaphosphorin-2-oxide) pretreatment produced a dramatic increase in the toxicity of soman in mice following the subcutaneous (s.c.) or intraperitoneal (i.p.) route of administration. This increase in soman toxicity was very highly correlated with inhibition of plasma aliesterase activity. Other enzymes (e.g. liver aliesterase and plasma cholinesterase) were inhibited by CBDP pretreatment; however, they did not appear to play a significant role in the potentiation of soman toxicity by CBDP. Liver aliesterase was not inhibited by doses of CBDP which produced significant increases in soman toxicity. Similarly, doses of Iso-OMPA, a selective inhibitor of pseudocholinesterase, which completely inhibited plasma cholinesterase, had no effect on soman toxicity. Pyridostigmine pretreatment which inhibited brain, diaphragm and plasma acetylcholinesterase 27, 57 and 60%, respectively, while not inhibiting plasma aliesterase, did not affect soman toxicity. The results of this study demonstrate that, in mice, plasma aliesterase is an extremely important detoxification route for soman.
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000201:enzymology; D043182:Carboxylesterase; D002265:Carboxylic Ester Hydrolases / Q000097:blood / Q000378:metabolism*; D003964:Diaphragm / Q000201:enzymology; D004912:Erythrocytes / Q000201:enzymology; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D008099:Liver / Q000201:enzymology; D008297:Male; D051379:Mice; D009130:Muscle, Smooth / Q000201:enzymology; D009943:Organophosphorus Compounds / Q000494:pharmacology / Q000633:toxicity*; D012999:Soman / Q000008:administration & dosage / Q000633:toxicity*; D013770:Tetraisopropylpyrophosphamide / Q000494:pharmacology
D009943:Organophosphorus Compounds; C000516:2-(2-cresyl)-4H-1-3-2-benzodioxaphosphorin-2-oxide; D013770:Tetraisopropylpyrophosphamide; D012999:Soman; D002265:Carboxylic Ester Hydrolases; D043182:Carboxylesterase; D000110:Acetylcholinesterase