Function of plasma and microsomal enzymes in soman toxicity.
Such organophosphorous (OP) nerve agents as sarin (isopropyl methylphosphonofluoridate) and soman (pinacolyl methylphosphonofluoridate) are effective inhibitors of acetylcholinesterases (AChE), butyrylcholinesterases (BChE) and carboxylesterases (CaE). The acute toxicity of these compounds in mammals is known to be mediated through inhibition of AChEs, which leads to increased acetylcholine (ACh) levels. The aim of this study was to compare the significance of the plasma CaEs, microsomal CaEs and CYP450 enzymes in detoxification of soman with and without physostigmine treatment. The mice received physostigmine (0.1 mg/kg body wt) intravenously (i.v.) 10 min prior to the intraperitoneal (i.p.) injection of soman (0.400-0.650 mg/kg body wt in olive oil). To avoid possible signs of poisoning, the animals received atropine sulfate (37.5 mg/kg body wt in saline) subcutaneously (s.c.) immediately after the soman administration. In the present study, the inhibitory effect of soman was greater in plasma CaE than in hepatic microsomal CaE fraction. In addition, soman or the combination of soman-physostigmine had no remarkable effect on the microsomal CaE or P4502B activities. In spite of this, however, the microsomal CaEs might offer more protection against multiple LD50s of soman.
Tuovinen
Kai
K
Department of Physiology, University of Kuopio, P. O. Box 1627, SF-70211 Kuopio, Finland. kai.tuovinen@uku.fi
D000818:Animals; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism; D002619:Chemical Warfare Agents / Q000493:pharmacokinetics* / Q000633:toxicity*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004359:Drug Therapy, Combination; D004798:Enzymes / Q000097:blood*; D008658:Inactivation, Metabolic; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D010830:Physostigmine / Q000008:administration & dosage / Q000494:pharmacology; D012999:Soman / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity*
D002619:Chemical Warfare Agents; D004798:Enzymes; D003577:Cytochrome P-450 Enzyme System; D012999:Soman; D010830:Physostigmine; D002265:Carboxylic Ester Hydrolases