Toxicological significance in the cleavage of esterase-beta-glucuronidase complex in liver microsomes by organophosphorus compounds.
Egasyn is an 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 the 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-beta-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 the 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 the 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 OP administration is much more sensitive biomarker than cholinesterase inhibition to acute intoxication of OPs and carbamates.
Biomedical Research Institute, Shiroi, Inba, Hiratsuka, Chiba, Japan. satohbri@plu.ifnet.or.jp
T
T
Satoh
S
S
Suzuki
N
N
Kawai
T
T
Nakamura
M
M
Hosokawa
D000818:Animals; D012721:Carbaryl / Q000633:toxicity; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000633:toxicity; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004950:Esterases / Q000378:metabolism*; D005278:Fenitrothion / Q000633:toxicity; D005966:Glucuronidase / Q000097:blood / Q000378:metabolism*; D006168:Guinea Pigs; D006801:Humans; D006868:Hydrolysis; D008252:Macaca fascicularis; D046911:Macromolecular Substances; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008647:Mesocricetus; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D009943:Organophosphorus Compounds / Q000633:toxicity*; D004849:Phenylphosphonothioic Acid, 2-Ethyl 2-(4-Nitrophenyl) Ester / Q000633:toxicity; D011722:Pyrethrins / Q000633:toxicity; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley
D002800:Cholinesterase Inhibitors; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D009943:Organophosphorus Compounds; D011722:Pyrethrins; D004849:Phenylphosphonothioic Acid, 2-Ethyl 2-(4-Nitrophenyl) Ester; C006166:phenothrin; D004950:Esterases; D002265:Carboxylic Ester Hydrolases; C009751:egasyn; D005966:Glucuronidase; D012721:Carbaryl; D005278:Fenitrothion