| 12767693 |
Kousba AA, Poet TS, Timchalk C: Characterization of the in vitro kinetic interaction of chlorpyrifos-oxon with rat salivary cholinesterase: a potential biomonitoring matrix. Toxicology. 2003 Jun 30;188(2-3):219-32.
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 approximately 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. |
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