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CHARACTERIZATION OF THE IN VITRO KINETIC INTERACTION OF CHLORPYRIFOS-OXON WITH RAT SALIVARY CHOLINESTERASE: A POTENTIAL BIOMONITORING MATRIX. (R828608)
Citation:
Kousba, A. A., T. S. Poet, AND C. Timchalk. CHARACTERIZATION OF THE IN VITRO KINETIC INTERACTION OF CHLORPYRIFOS-OXON WITH RAT SALIVARY CHOLINESTERASE: A POTENTIAL BIOMONITORING MATRIX. (R828608). TOXICOLOGY. American Chemical Society, Washington, DC, 188(2):219-232, (2003).
Description:
The primary mechanism of action for organophosphorus (OP) insecticides such as chlorpyrifos (CPF) involves the inhibition of acetylcholinesterase (AChE) by their active oxon metabolites resulting in a wide range of neurotoxic effects. These oxons also inhibit other cholinesterases (ChE) such as butyrylcholinesterase (BuChE), which represents a detoxification mechanism and a potential biomarker for OP insecticide exposure/response. Salivary biomonitoring has recently been explored as a practical method for examination of chemical exposure, however, there are few studies exploring the use of saliva for OP insecticides. To evaluate the use of salivary ChE as a biological monitor for OP insecticide exposure, a modified Ellman assay in conjunction with a pharmacodynamic model was used to characterize salivary ChE in adult male Sprague–Dawley rats. Comparison of rat saliva, brain, and plasma ChE activity in the presence of selective inhibitors of AChE and BuChE (BW284C51 and iso-OMPA, respectively) with different ChE substrates indicated that rat salivary ChE activity is primarily associated with BuChE (>95%). Further characterization of rat salivary BuChE kinetics yielded an average total BuChE active site concentration of 1.20±0.13 fmol ml-1 saliva, an average reactivation rate constant (Kr) of 0.070±0.008 h-1, and an inhibitory rate constant (Ki) of ~9 nM-1 h-1. The pharmacodynamic model successfully described the in vitro BuChE activity profile as well as the kinetic parameters. These results support the potential utility of saliva as a biomonitoring matrix for evaluating occupational and environmental exposure to CPF and other OP insecticides.
Author Keywords: Saliva; Cholinesterase; Organophosphate insecticide; Chlorpyrifos; Chloropyrifos-oxon; Biomonitoring