Detoxification of soman in the perfused rat liver: quantitative uptake and stereoisomer metabolism.
The detoxification of soman (1,2,2-dimethyl-propyl methylphosphonofluoridate) was measured in rat livers, using hemoglobin-free, non-recirculating perfusion in situ. Since the detoxification processes may differ in perivenous and periportal zones of liver parenchyma, soman uptake, stereoselective metabolism and inhibition of esterases were compared in antegrade and retrograde perfusion experiments. At low concentrations of soman (up to about 10 mumol l-1 for 5 min) soman was taken up by the liver nearly quantitatively. About 5% recovery rate in the perfusate corresponded well to the intrahepatic shunt flow. Infusions of higher amounts yielded increasing recovery rates. The racemic infusion medium contained the four isomers of soman, C(-)P(-) to C(+)P(+), in nearly identical amounts, whereas in the effluent perfusate only P(-) isomers were found. Even small amounts of soman (5-120 nmol g-1 liver wet weight) caused significant inhibition of hepatic aliesterase activity. Doses higher than 200 nmol g-1 suppressed esterase activity by more than 90%. No essential differences in soman uptake, stereoselective metabolism or inhibition of esterases were found between antegrade and retrograde perfusion experiments.
Wahlländer
A
A
Institut für Pharmakologie und Toxikologie, Akademie des Sanitäts -und Gesundheitswesens der Bundeswehr, Garching/Hochbrück, Federal Republic of Germany.
Szinicz
L
L
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004950:Esterases / Q000037:antagonists & inhibitors / Q000378:metabolism; D008658:Inactivation, Metabolic; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D012999:Soman / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D013237:Stereoisomerism
D012999:Soman; D004950:Esterases