Toxicological Aspects of Carboxylesterases -A Sensitive Biomarker of Organophosphate Toxicity-

  • Satoh, Tetsuo (Biomedical Research Institute, Laboratory of Biochemical Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, Chiba University) ;
  • Suzuki, Satoshi (Biomedical Research Institute) ;
  • Hosokawa, Masakiyo (Laboratory of Biochemical Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, Chiba University)
  • 발행 : 1998.11.01

초록

Egasyn is accessory protein of ${\beta}$-glucuronidase(${\beta}$-G) in the liver microsomes. Liver microsomal ${\beta}$-G is stabilized within the luminal site of the microsomal vesicles by complexation with egasyn which is one of carboxylesterase isozymes. We investigated the effects of organophosphorus compounds(OPs) such as insecticides on the dissociation of egasyn-${\beta}$-glucuronidase(EG) complex. The EG complex was easily dissociated by administration of OPs, i.e., Fenitrothion, EPN, Phenthionate, and bis-p-nitrophenyl phosphate(BNPP), and resulting ${\beta}$-G dissociated was released into blood, leading to the rapid and transient increase of plasma ${\beta}$-G level with a concomitant decrease of liver microsomal ${\beta}$-G level. In a case of phenthionate treatment, less increase in plasma ${\beta}$-G level was observed, as compared with those of other OPs. This may be explained by a fact that phenthionate was easily hydrolyzed by carboxylesterase. Similarly, carbamate insecticides such as Carbaryl caused rapid increase of plasma ${\beta}$-G level. In contrast, no significant increase of plasma ${\beta}$-G level was observed when pyrethroid insecticides were administered to rats. This is due to a fact that pyrethroids such as Phenthrin and Allethrin were easily hydrolyzed by A-esterase as well as carboxylesterase. On the other hand, addition of OPs to the incubation mixture containing liver microsomes caused the release of ${\beta}$-G from microsomes to the medium. From these in vivo and in vitro data, it is concluded that increase of the plasma ${\beta}$-G level after OPs administration is much more sensitive biomarker than cholinesterase inhibition to acute intoxication of OPs and carbamates.

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