Release of liver microsomal beta-glucuronidase from hepatocytes in vitro and in vivo by organophosphates and hepatotoxic agents.
Liver microsomal beta-glucuronidase is stabilized within microsomal vesicles by complexation with the accessory protein, named egasyn. In this study, we showed that egasyn is identical to one of the carboxylesterase isozymes and organophosphorus and carbamate insecticides, acetanilide which is a specific substrate of egasyn and halothane caused a rapid dissociation of the egasyn-microsomal beta-glucuronidase complex when administered in vivo or when added in vitro to isolated hepatocytes. The dissociation was relatively specific to organophosphates, carbamates, but not pyrethroids. Dissociation of the egasyn-beta-glucuronidase complex in vivo by organophosphates was followed by massive and rapid secretion of microsomal beta-glucuronidase into plasma. From these results, we concluded that release of liver microsomal beta-glucuronidase is the most rapid and sensitive marker to organophosphorus or carbamate insecticide-induced intoxication.
Laboratory of Biochemical Pharmacology and Biotoxicology, Faculty of Pharmaceutical Sciences, Chiba University, Japan.
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Satoh
D000083:Acetanilides / Q000633:toxicity; D000595:Amino Acid Sequence; D000818:Animals; D002219:Carbamates; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology*; D005966:Glucuronidase / Q000378:metabolism*; D006221:Halothane / Q000633:toxicity; D007306:Insecticides / Q000633:toxicity; D008862:Microsomes, Liver / Q000201:enzymology*; D008969:Molecular Sequence Data; D009596:Nitrophenols / Q000378:metabolism; D009943:Organophosphorus Compounds / Q000378:metabolism / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains
D000083:Acetanilides; D002219:Carbamates; D007306:Insecticides; D009596:Nitrophenols; D009943:Organophosphorus Compounds; C008644:nitrophenylphosphate; D002265:Carboxylic Ester Hydrolases; D005966:Glucuronidase; D006221:Halothane