Extremely sensitive biomarker of acute organophosphorus insecticide exposure

Abstract

Egasyn-βglucuronidase complex is located at the luminal site of liver microsomal endoplasmic reticulum. When organophosphorus insecticides (OP) are incorporated into the liver microsomes, they become tightly bound to egasyn, a carboxylesterase isozyme, and subsequently, β-glucuronidase (BG) is dissociated and released into blood. Consequently, the increase in plasma BG activity becomes a good biomarker of OP exposure. Thus, the single administration of EPN (O-ethyl O-p-nitrophenylphenylphosphonothioate), acephate and chlorpyrifos increased plasma BG activity in approximately 100-fold the control level in rats. The increase in plasma BG activity after OP exposure is a much more sensitive biomarker of acute OP exposure than acetylcholinesterase (AChE) inhibition.

Keywords

carboxylesterase egasyn β-glucuronidase organophosphorus insecticide

References

1 Chambers JE . Organophosphate-chemistry. Fate and Effects , Chambers JE , Levi PE Eds., New York: Academic Press , 1992.

2 DuBois KP . New rodencidal compounds . J Am Pharm Assoc 1948; 37: 307-310 .

3 DuBois KP , Doull J , Saleno PR , Coon JM . Studies on the toxicity and mechanism of action of p-nitrophenyldiethyl-thionophosphate (Parathion) J Pharmacol Exp Ther 1949; 95: 75-91

4 Swank RT ., Paigen K. Biochemical and genetic evidence for a macromolecularglucuronidase complex in microsomal membranes . J Mol Biol 1973; 77: 371-389 .

5 Medda S , Takeuchi K , Devore-arter D , Con Deimling O , Heymum E , Swank RT . An accessory protein identical to mouse egasyn in complexed with rat β-glucuronidase and is identical to rat esterase 3 J Biol Chem 1987; 262: 7248-7253

6 Hosokawa M ., Maki T , Satoh T.

Multiplicity and regulation of hepatic microsomal carboxylesterases in rats

Mol Pharmacol 1987; 31: 579-584

7 Hosokawa M ., Maki T , Satoh T.

Characterization of molecular species of liver microsomal carboxylesterases of several animal species and humans

Arch Biochem Biophys 1990; 277: 219-227

8 Satoh T ., Hosokawa M.

The mammalian carboxylesterases: From molecules to functions

Ann Rev Pharmacol Toxicol 1998; 38: 257-288

9 Satoh T ., Suzuki S , Kawai N , Nakamura T , and Hosokawa M.

Toxicological significance in the cleavage of esterase-bglucuronidase complex in liver microsomes by organophosphorus compounds

Chem Biol Interact 1999; 119-120: 471-478

10.

10 Satoh T . and Hosokawa M.

Organophosphates and their impact on the global environment

Neurotoxicology 2000; 21: 223-227

11.

11 Satoh T ., Palmer T , Bosron WF , Sanghani SP , Hosokawa M and LaDu, B. Current progress on esterases: From molecular structure to function . Drug Metab Dispos 2002; 30: 488-493 .

12.

12 Brandt EJ , Elliott RW , Swank RT . Defective lysosomal enzyme secretion in kidneys of Chediak-Higashi (beige) mice . J Cell Biol 1975, 67: 774-788 .