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Title: AGE-RELATED BRAIN CHOLINESTERASE INHIBITION KINETICS FOLLOWING IN VITRO INCUBATION WITH CHLORPYRIFOS-OXON AND DIAZINON-OXON

Abstract

Chlorpyrifos and diazinon are two commonly used organophosphorus (OP) insecticides, and their primary mechanism of action involves the inhibition of acetylcholinesterase (AChE) by their metabolites chlorpyrifos-oxon (CPO) and diazinon-oxon (DZO), respectively. The study objectives were to assess the in vitro age-related inhibition kinetics of neonatal rat brain cholinesterase (ChE) by estimating the bimolecular inhibitory rate constant (ki) values for CPO and DZO. Brain ChE inhibition and ki values following CPO and DZO incubation with neonatal Sprague-Dawley rats rat brain homogenates were determined at post natal day (PND) -5, -12 and -17 and compared with the corresponding inhibition and ki values obtained in the adult rat. A modified Ellman method was utilized for measuring the ChE activity. Chlorpyrifos-oxon resulted in greater ChE inhibition than DZO consistent with the estimated ki values of both compounds. Neonatal brain ChE inhibition kinetics exhibited a marked age-related sensitivity to CPO, where the order of ChE inhibition was PND-5 > PND-7 > PND-17 with ki values of 0.95, 0.50 and 0.22 nM-1hr-1, respectively. In contrast, DZO did not exhibit an age-related inhibition of neonatal brain ChE, and the estimated ki value at all PND ages was 0.02 nM-1hr-1. These results demonstrated an age- and chemical-related OP-selectivemore » inhibition of rat brain ChE which may be critically important in understanding the potential sensitivity of juvenile humans to specific OP exposures.« less

Authors:
; ;
Publication Date:
Research Org.:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
900914
Report Number(s):
PNWD-SA-7486
Journal ID: ISSN 1096-6080; TOSCF2; TRN: US200711%%636
DOE Contract Number:  
AC05-76RL01830
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicological Sciences, 95(1):147-155; Journal Volume: 95; Journal Issue: 1
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; ADULTS; BRAIN; CHOLINESTERASE; HOMOGENATES; IN VITRO; INCUBATION; INSECTICIDES; JUVENILES; KINETICS; METABOLITES; SENSITIVITY; agricultural chemicals; ADME; cholinesterase

Citation Formats

Kousba, Ahmed A., Poet, Torka S., and Timchalk, Chuck. AGE-RELATED BRAIN CHOLINESTERASE INHIBITION KINETICS FOLLOWING IN VITRO INCUBATION WITH CHLORPYRIFOS-OXON AND DIAZINON-OXON. United States: N. p., 2007. Web. doi:10.1093/toxsci/kfl123.
Kousba, Ahmed A., Poet, Torka S., & Timchalk, Chuck. AGE-RELATED BRAIN CHOLINESTERASE INHIBITION KINETICS FOLLOWING IN VITRO INCUBATION WITH CHLORPYRIFOS-OXON AND DIAZINON-OXON. United States. doi:10.1093/toxsci/kfl123.
Kousba, Ahmed A., Poet, Torka S., and Timchalk, Chuck. Mon . "AGE-RELATED BRAIN CHOLINESTERASE INHIBITION KINETICS FOLLOWING IN VITRO INCUBATION WITH CHLORPYRIFOS-OXON AND DIAZINON-OXON". United States. doi:10.1093/toxsci/kfl123.
@article{osti_900914,
title = {AGE-RELATED BRAIN CHOLINESTERASE INHIBITION KINETICS FOLLOWING IN VITRO INCUBATION WITH CHLORPYRIFOS-OXON AND DIAZINON-OXON},
author = {Kousba, Ahmed A. and Poet, Torka S. and Timchalk, Chuck},
abstractNote = {Chlorpyrifos and diazinon are two commonly used organophosphorus (OP) insecticides, and their primary mechanism of action involves the inhibition of acetylcholinesterase (AChE) by their metabolites chlorpyrifos-oxon (CPO) and diazinon-oxon (DZO), respectively. The study objectives were to assess the in vitro age-related inhibition kinetics of neonatal rat brain cholinesterase (ChE) by estimating the bimolecular inhibitory rate constant (ki) values for CPO and DZO. Brain ChE inhibition and ki values following CPO and DZO incubation with neonatal Sprague-Dawley rats rat brain homogenates were determined at post natal day (PND) -5, -12 and -17 and compared with the corresponding inhibition and ki values obtained in the adult rat. A modified Ellman method was utilized for measuring the ChE activity. Chlorpyrifos-oxon resulted in greater ChE inhibition than DZO consistent with the estimated ki values of both compounds. Neonatal brain ChE inhibition kinetics exhibited a marked age-related sensitivity to CPO, where the order of ChE inhibition was PND-5 > PND-7 > PND-17 with ki values of 0.95, 0.50 and 0.22 nM-1hr-1, respectively. In contrast, DZO did not exhibit an age-related inhibition of neonatal brain ChE, and the estimated ki value at all PND ages was 0.02 nM-1hr-1. These results demonstrated an age- and chemical-related OP-selective inhibition of rat brain ChE which may be critically important in understanding the potential sensitivity of juvenile humans to specific OP exposures.},
doi = {10.1093/toxsci/kfl123},
journal = {Toxicological Sciences, 95(1):147-155},
number = 1,
volume = 95,
place = {United States},
year = {Mon Jan 01 00:00:00 EST 2007},
month = {Mon Jan 01 00:00:00 EST 2007}
}