Disease relevance of CCRIS 7774

• The higher A-esterase activity with chlorpyrifos-oxon than paraoxon may be a major determinant in the observed lower acute toxicity of chlorpyrifos than parathion [1].

High impact information on CCRIS 7774

• Compared with their wild-type littermates, PON1-deficient mice were extremely sensitive to the toxic effects of chlorpyrifos oxon, the activated form of chlorpyrifos, and were more sensitive to chlorpyrifos itself [2].
• Therefore, it was surprising that the predominant mouse brain protein labeled in vitro by [(3)H-ethyl]CPO (1 nM) (designated CPO-binding protein or CPO-BP) is not one of these known OP toxicant targets [3].
• Role of genetic polymorphism of human plasma paraoxonase/arylesterase in hydrolysis of the insecticide metabolites chlorpyrifos oxon and paraoxon [4].
• Pretreatment of BSA with 5 mM paraoxon, chlorpyrifos oxon, or 1 mM diisopropylfluorophosphate did not alter this activity, suggesting that these reactions resulted from an esterase-like capacity of BSA, and not from phosphorylation of BSA by these oxons [5].
• MATERIALS AND METHODS: Homozygous reeler (RL), heterozygous (HZ), and wild-type (WT) mice were prenatally exposed to chlorpyrifos-oxon (CPF-O), the active metabolite of chlorpyrifos, or to vehicle (prenatal controls) on gestation days 14-16, that is, during a peak period of neurogenesis in the cerebral cortex [6].

Biological context of CCRIS 7774

• The oxon metabolite bound at low concentrations to muscarinic receptors labeled by the muscarinic agonist [3H] cis-methyldioxolane; chlorpyrifos oxon bound with an IC50 value of 22.1 +/- 3.6 nM [7].
• The altering of postreceptor signal transduction by chlorpyrifos oxon may interfere with normal cellular signaling, thereby disturbing neurological function [7].
• The rates of hydrolysis of diazoxon, chlorpyrifos-oxon, and paraoxon varied 5.7-, 16-, and 56-fold, respectively, regardless of PON1-192 genotype [8].
• Comparison of chlorpyrifos-oxon and paraoxon acetylcholinesterase inhibition dynamics: potential role of a peripheral binding site [9].
• Age-Related Brain Cholinesterase Inhibition Kinetics following In Vitro Incubation with Chlorpyrifos-Oxon and Diazinon-Oxon [10].

Anatomical context of CCRIS 7774

• We have tested this hypothesis in vitro with PC12 cells, which lack the enzymes necessary to produce chlorpyrifos oxon, the metabolite that inhibits cholinesterase [11].
• Chlorpyrifos, chlorpyrifos-oxon, and diisopropylfluorophosphate inhibit kinesin-dependent microtubule motility [12].
• The aims of this study were to define the influence of PON1-192 genotype and phenotype on the capacity of human liver microsomes (n = 27) to detoxify the oxons diazoxon, chlorpyrifos-oxon, and paraoxon [8].
• The most potent in vitro inhibitors for human erythrocyte and mouse brain APH are DFP (IC(50) 11-17 nM), chlorpyrifos oxon (IC(50) 21-71 nM), dichlorvos (IC(50) 230-560 nM), naled (IC(50) 370-870 nM), and their analogs with modified alkyl substituents [13].
• The effects of repeated postnatal exposure to CPS and its metabolite chlorpyrifos-oxon (CPO) on total muscarinic acetylcholine receptor (mAChR) binding, nerve growth factor (NGF) levels, and brain derived neurotrophic factor (BDNF) levels in the forebrain of neonatal rats were investigated [14].

Associations of CCRIS 7774 with other chemical compounds

• Spectropho-tometric assay detected A-esterase activity toward paraoxon, chlorpyrifos-oxon, and phenyl acetate in the final preparation [15].
• Paraoxon and chlorpyrifos-oxon, the active metabolites of the organophosphorus insecticides parathion and chlorpyrifos, respectively, are hydrolyzed by an "A"-esterase, paraoxonase, which is present in the sera of several mammalian species [16].
• The aim of the present study was to evaluate the in vitro modulation of muscarinic autoreceptor function by the organophosphorus (OP) anticholinesterases chlorpyrifos oxon, paraoxon, and methyl paraoxon [17].
• Individuals with the PON1-192RR genotype preferentially hydrolyzed paraoxon (p < 0.01), and the R allele was associated with higher hydrolytic activity toward chlorpyrifos-oxon, but not diazoxon [8].
• At elevated pH, both CP and CPO are susceptible to alkaline hydrolysis and degrade to 3,5,6-trichloro-2-pyridinol (TCP), a stable end product [18].

Gene context of CCRIS 7774

• Inhibition of acetylcholinesterase and butyrylcholinesterase by chlorpyrifos-oxon [19].
• Preincubation of CYP3A4 with chlorpyrifos, but not chlorpyrifos-oxon, resulted in 98% inhibition of TST metabolism [20].
• Mice treated with DEET demonstrated induced levels of the CYP2B family, increased hydroxylation, and a 2.4-fold increase in the metabolism of chlorpyrifos to chlorpyrifos-oxon, a potent anticholinesterase [21].
• Even at PN4, when PON1 levels were low in wild-type mice, PON1(-/-) mice were more sensitive to inhibition of brain cholinesterase by CPO [22].
• CPS can be activated by cytochrome P450 (CYP) through a desulfuration reaction to form chlorpyrifos-oxon (CPO), a potent anticholinesterase [23].

Analytical, diagnostic and therapeutic context of CCRIS 7774

• Previous studies had indicated that the levels of serum PON1 in gene therapy with adenoviral vector could decrease the toxicity of CPO [24].
• Following single-pass perfusion of mouse livers in situ with the organophosphate pesticide chlorpyrifos, the cholinesterase inhibitor chlorpyrifos oxon could not be detected in effluent perfusate [25].
• Strains (BESS and BKRR) homogeneous for each variant were isolated and their relative susceptibilities to methomyl, chlorpyrifos, and chlorpyrifos-oxon assessed by topical application bioassay [26].
• The effect of CPF and CPO on gene expression in Caco-2 cells was tested as a function of time using RT-PCR and competitive PCR (compPCR) techniques [27].
• Determination of the analytes in spiked river water samples by use of the dmAChE biosensor resulted in recoveries from 50 to 90 % for chlorpyrifos oxon at levels of 20 to 40 nmol L(-1), 50 to 100 % for paraoxon at 0.6 to 0.8 micro mol L(-1), and 140 to 190 % for malaoxon at 0.6 to 1.2 micro mol L(-1) [28].

References