Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.1.8 (cholinesterase)
 12,691 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies have shown that a single oral pretreatment of rats with the organophosphorus insecticide 2-chloro-1-(2,4-dichlorophenyl)vinyl diethyl phosphate (chlorfenvinphos, CVP) afforded protection against the toxicity of a subsequent challenge with the same compound within 24 hr. This protection may be due to the reduction in brain cholinesterase inhibition caused by the decrease in plasma CVP concentration. The purpose of this study was to investigate the mechanism of the decrease in plasma CVP concentration in relation to metabolic induction. CVP was preferentially metabolized by a liver microsomal fraction with an NADPH-generating system, compared with serum or kidney subcellular fractions. A single oral 24-hr pretreatment with CVP (15 mg/kg) increased the oral LD50 of its next dosage to threefold. The same treatment also increased CVP metabolism (to 178%), cytochrome P450 content (to 130%), cytochrome P450 reductase activity (to 130%), cytochrome b5 content (to 121%), and cytochrome P450-linked activities such as aminopyrine demethylase (to 140%) and aniline hydroxylase (to 127%) in the hepatic microsomal fraction. A single oral 24-hr pretreatment of phenobarbital (50 mg/kg), which is known as an inducer of cytochrome P450, increased the oral LD50 of CVP and all the related metabolic parameters listed above in an order of magnitude similar to that of CVP, although the increments induced by the phenobarbital treatment were greater than those induced by the CVP treatment. These results indicate that the increase in hepatic CVP metabolism may be due to the induction of the hepatic cytochrome P450 system caused by the single oral short-term treatment with CVP. This induction may be one of the reasons for the decrease in plasma CVP concentration which may be responsible for the reduction in toxicity of its next dosage.
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PMID:Metabolic induction of the hepatic cytochrome P450 system by chlorfenvinphos in rats. 176 23

The aim of the present study was to investigate persistent neurobehavioural effects of repeated low-level exposure to chlorphenvinphos ((2-chloro-1-(2,4-dichlorophenyl) vinyl diethyl phosphate-CVP) in rats. The rats received 10 i.p. injections of CVP at daily doses of 0.5 mg/kg or 1.0 mg/kg (one injection/day, five days/week) which corresponded to 1/20 and 1/10 of LD50, respectively, for this species. In a part of the rats, cholinesterase (ChE) activity in blood (plasma and erythrocytes), and in the selected brain regions was determined at arbitrarily chosen time after the last exposure. The determinations showed that the level of ChE inhibition was dose-related, but the compartments studied differed in the magnitude of this effect. The differences in the level of ChE inhibition between the compartments were particularly evident in rats which had received CVP at the 1.0 mg/kg dose; in these animals 3 h after exposure the ChE activity in erythrocytes, plasma and the brain corresponded to 78%, 48% and 67-70%, respectively, of the control value. Enzyme activity returned to the control level after 14 days in plasma and after 35 days in erythrocytes. In rats receiving CVP at daily doses of 0.5 mg/kg, ChE activity in plasma was decreased by 40.8% and that in erythrocytes by 21.4% 3 h after the last exposure. The activity of ChE in plasma returned to the control level within four days and that in erythrocytes within 14 days. In these rats, in all the brain regions studied except brainstem, ChE activity was not reduced significantly. In rats selected for behavioural tests, the following behavioural aspects were investigated: response to novelty in an open field, acquisition and extinction of a one-way active avoidance response, and the magnitude and persistence of the footshock-induced analgesia (hot-plate test). Testing in the open field was performed before the exposure and then 1, 3 and 6 weeks after the last exposure. The remaining tests were performed after the exposure. The interval between testing and the last CVP injection was sufficient for recovery of ChE activity. It has been found that in rats of both exposure groups the response to novelty in the open field, i.e. the increase in locomotor and exploratory activity in the presence of a new object, was reduced, albeit nonsignificantly, compared to the unexposed animals. In rats which received CVP at the dose of 1.0 mg/kg, acquisition of the one-way active avoidance response was facilitated. No differences between groups were found during extinction of this response. In the hot-plate test, in rats exposed repeatedly to 1.0 mg/kg CVP, the footshock-induced increase in the latency of the paw-lick response to heat (54.5 degrees C) was stronger and more persistent than in the unexposed animals. The above results show that some neurobehavioural effects of exposure to organophosphorous (OP) compounds may be detected after a time sufficient for recovery of ChE activity.
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PMID:Long-term behavioural effects of a repeated exposure to chlorphenvinphos in rats. 1046

We investigated the effect of acute exposure to chlorphenvinphos (CVP) (2-chloro-1 (2,4-dichlorophenyl)-vinyl-diethyl-phosphate), an organophosphate anticholinesterase, on the amphetamine- and scopolamine-induced open-field locomotion in Wistar rats. CVP was administered at a single i.p. dose of 1.0 mg/kg (1/10 of LD50). In part of the rats cholinesterase (ChE) was determined. Three hours after CVP injection, the ChE activity decreased by about 27%. It returned to the preinjection level within 14 days after the exposure. In the behavioural part of the experiment, the animals were challenged with 1.0 mg/kg amphetamine or 0.75 mg/kg scopolamine three weeks after CVP exposure, i.e. after a period of time sufficient for cholinesterase recovery. It has been found that in the CVP-exposed rats, the behavioural responses to amphetamine or scopolamine challenge (the increase in locomotor activity) was significantly reduced compared to the controls. This suggests that acute exposure to CVP produced an increase in cholinergic activity which persisted long after ChE activity had returned to normal.
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PMID:Long-term effects of acute exposure to chlorphenvinphos on behavioural responsiveness to amphetamine and scopolamine in rats. 1110 45