Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.1.7 (acetylcholinesterase)
28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dermal and oral toxicities of azamethiphos were determined in two organophosphate-resistant and one susceptible strain of houseflies, Musca domestica L. The 594vb strain was 1,967-fold more resistant to azamethiphos when compared with the susceptible Chemical Specialties Manufacturers Association (CSMA) strain by dermal application. When the compound was administered orally to the 594vb strain, we observed only a 15-fold resistance. In contrast, the Yachiyo strain, which show 1,500-fold resistance to diazinon and which has known multiple mechanisms for organophosphate resistance, showed only 6-fold resistance to azamethiphos by topical application and 4-fold resistance by oral administration. Azamethiphos administered dermally and orally was equally toxic to the CSMA and Yachiyo strains. However, when azamethiphos was administered to the 594vb strain, the insecticide was 71 times more toxic orally than by the dermal route. This result indicated involvement of a cuticular penetration factor in the resistance mechanism. The effect on azamethiphos toxicity of piperonyl butoxide (PB), an inhibitor of the monooxygenases, and tributylphosphorotrithioate (DEF), an esterase inhibitor, was investigated in the three strains. Pretreatment of the flies with PB, DEF, or PB+DEF before topical application of azamethiphos resulted in a significant decrease in LD50s in all the strains. The degree of synergism, however, varied depending upon the strains and the synergists. Similar results were obtained when azamethiphos was administered orally following pretreatment of the flies with PB+DEF. We attribute the high level of azamethiphos resistance in the 594vb strain partly to increased degradation by oxidative and hydrolytic enzymes. The hydrolytic enzymes are more important, but other factors including reduced cuticular penetration and insensitive acetylcholinesterase may be involved.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of synergists on the oral and topical toxicity of azamethiphos to organophosphate-resistant houseflies (Diptera: Muscidae). 151 4

The in vivo and in vitro fate of [14C]carbaryl was compared in adult male and female house flies from an insecticide-susceptible (S) strain and a resistant (R) strain with multiple resistance to different classes of insecticides. Cuticular penetration of topically applied carbaryl (0.01 microgram/insect) was very rapid and rates were essentially the same among males and females of both strains. Rates of penetration were dramatically reduced as the concentration of applied carbaryl was increased over a range of 0.01-5.0 micrograms/insect. In vivo and in vitro tests demonstrated that the R strain had an enhanced capability for the metabolic degradation of carbaryl. In evaluations of topical toxicity and in vitro metabolic degradation, coadministration of the metabolic synergists piperonyl butoxide (a microsomal oxidase inhibitor) and S,S,S-tributyl phosphorothioate (DEF, an esterase inhibitor) with carbaryl provided conclusive evidence that microsomal oxidases were the major factor in enhanced metabolism and that hydrolytic enzymes had only a minor effect. Studies of the in vitro inhibition of acetylcholinesterase (AChE) activity by carbaryl demonstrated that there was no difference between males and females of a given strain and that the R strain AChE was considerably less sensitive to inhibition. These tests also indicated that homogenates of brains from the R strain contained more than one form of AChE with different sensitivities to the inhibitor. This information and results of toxicity tests with other insecticides suggest that the R strain is not homozygous in its resistance to carbaryl.
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PMID:Interactions of carbaryl with susceptible and multiresistant house flies (Diptera: Muscidae). 184 92

Electroretinograms (ERGs) were recorded in vitro from eyes of rainbow trout that had received intraperitoneal injections of either TOCP (triorthocresyl phosphate) or DEF (S, S, S-tributyl phosphorotrithioate). Data obtained after 24 h indicated that these organophosphates caused alterations in four of five ERG parameters in the case of TOCP and all five parameters in the DEF treated specimens. These data were compared with data obtained from experiments with eserine and carbachol and led to the conclusion that the effects of the organophosphates on the retina were independent of any cholinesterase inhibitor activity of the compounds. These organophosphates affect (a) the non-cholinergic photoreceptor layer of the retina which produces the a-wave ERG component, and (b) the other neural layers of the retina known to be responsible for generation of the b-wave component. Based on data obtained 15 days after exposure there was no evidence that TOCP or DEF has any delayed neurotoxic effect on the retina of rainbow trout.
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PMID:Action of organophosphates on the electroretinogram of rainbow trout. 384 30

The changes in brain acetylcholinesterase (AChE), acid phosphatase (APase), and 2',3'-cyclic nucleotide-3'-phosphohydrolase (CNP), and plasma butyrylcholinesterase (BuChE) activities were investigated in hens treated with a single, dermal dose (100-1000 mg/kg) of S,S,S-tri-n-butyl phosphorotrithioate (DEF). Three control groups consisted of hens left untreated, given a single, dermal dose of 500 mg/kg tri-o-cresyl phosphate (TOCP, positive control for organophophorous compound-induced delayed neurotoxicity), or 10 mg/kg O,O-diethyl O-4-nitrophenyl phosphorothioate (parathion, negative control). Brain AChE activity, determined 28 days after application, was significantly inhibited in hens given 500-1,000 mg/kg DEF and in TOCP- and parathion-treated hens. In contrast, brain APase and CNP activities were significantly higher in all treatments as compared with those of the untreated hens. Parathion, however, caused the least increase in these enzymatic activities as compared to DEF or TOCP. A single, dermal dose of DEF or TOCP also caused an initial decrease in plasma BuChE activity with maximum depression of enzymatic activity observed 1 to 7 days after administration. This decrease was dose dependent and the enzymatic activity showed partial recovery with time. Hens treated with single, dermal doses of DEF, ranging from 250 to 1000 mg/kg, developed ataxia which progressed to paralysis in some hens. Histopathologic examination revealed axon and myelin degeneration of the spinal cord and peripheral nerves of some hens. The severity and frequency of the neuropathologic lesions were dose dependent. Neurologic dysfunctions and neuropathologic lesions seen in DEF-treated hens were similar to those exhibited in TOCP-treated hens. While parathion produced acute cholinergic effects, it did not cause delayed neurotoxicity. The changes in brain and plasma enzymes are discussed in relation to their role in the pathogenesis of DEF-induced delayed neurotoxicity.
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PMID:Brain acetylcholinesterase, acid phosphatase, and 2',3'-cyclic nucleotide-3'-phosphohydrolase and plasma butyrylcholinesterase activities in hens treated with a single dermal neurotoxic dose of S,S,S-tri-n-butyl phosphorotrithioate. 395 29

5 cytochrome P-450 isozymes were purified from the livers of uninduced mice and reconstituted with purified NADPH cytochrome P-450 reductase and phospholipid. The pesticides parathion, fonofos, DEF, Mocap and profenofos were oxidized by the reconstituted monooxygenase system to form acetylcholinesterase (AChE) inhibitors. The bioactivation varied with the pesticide substrate and the cytochrome P-450 isozyme. Aldrin epoxidation occurred with all 5 isozymes, with cytochrome P-450 A1 being the most active. All fraction metabolized the pesticide synergist piperonyl butoxide (PBO) to form an inhibitory cytochrome P-450-PBO-metabolite complex. The reduced complex produced a spectrum in the Soret region which was characteristic for each of the cytochrome P-450 isozymes. Inhibition of aldrin epoxidation by PBO was found to be unrelated to the nature of the Soret spectrum.
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PMID:Oxidation of pesticides by purified cytochrome P-450 isozymes from mouse liver. 398 73

The differential effects of oral and dermal administration of single doses of 100 to 1000 mg/kg S,S,S-tri-n-butyl phosphorotrithioate (DEF) on nonspecific esterases and liver metabolism enzymes were investigated one day following administration. O,O-Diethyl O-(4-nitrophenyl) phosphorothioate (parathion) and tri-o-cresyl phosphate (TOCP) were used as negative and positive controls for organophosphorus-induced delayed neurotoxicity (OPIDN). Brain acetylcholinesterase was significantly inhibited with topical doses of 500 and 1,000 mg/kg of DEF and with orally and dermally applied parathion. Plasma cholinesterase and liver microsomal carboxylesterase activities were significantly reduced from control in all treatment groups. Neurotoxic esterase (NTE) was significantly decreased from control with topical dosing of 200, 500, and 1000 mg/kg DEF and with TOCP treatments. Oral doses of DEF increased cytochrome P-450 content by 70 to 200% while dermal application caused a 200 to 325% increase over control. p-Chloro-N-methylaniline demethylase was also increased by DEF treatments but to a lesser extent than that of aniline hydroxylase or cytochrome P-450 content. TOCP and parathion had no significant effect on liver microsomal oxidative enzymes. Liver microsomal proteins from hens treated with phenobarbital (PB), 3-methylcholanthrene (3MC), or DEF were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. A striking increase in a 49K protein band in microsomes from PB and DEF (616 and 338%, respectively) treated hens was seen, while the 55K protein band showed an 861% increase in microsomes from 3MC-treated hens. In conclusion, dermally applied DEF was more effective in inhibiting esterases and inducing cytochrome P-450 than orally administered DEF; toxicity was directly related to the dose and route of administration.
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PMID:Induction of hepatic microsomal cytochrome P-450 and inhibition of brain, liver, and plasma esterases by an acute dose of S,S,S-tri-n-butyl phosphorotrithioate (DEF) in the adult hen. 671 May 30

n-Butyl mercaptan (nBM) is a breakdown product of S,S,S,-tri-n-butyl phosphorotrithioate (DEF) and S,S,S-tri-n-butyl phosphorotrithioite (merphos) in hens and in the environment. n-Butyl disulfide (nBD) is an oxidation product of nBM. A single 500 mg/kg dose of nBM and nBD was administered in gelatin capsules to groups of five 12-month old laying hens. A third group (five hens) was given gelatin capsules. One day after administration, the hens exhibited weakness which progressed to unsteadiness and inability to stand by the third day. These signs were accompanied by a pale comb 18--24 hr after dosing, which changed to dark color at 48 hr. Treated hens improved with time. Heinz bodies and extensive erythrocyte deformation and lysis were observed in blood smears taken from hens 24 and 48 hr after treatment. Hemoglobin concentration, packed cell volume, erythrocytes, and glucose-6-phosphate dehydrogenase activity were significantly lower than controls, while methemoglobin was significantly higher. As the clinical condition of these hens improved, these hematologic changes disappeared. nBM caused an initial increase in plasma butyrylcholinesterase activity which was dose-dependent and returned to normal by the end of the 28-day experiment. Also, brain acetylcholinesterase activity was not different from that of the control at termination.
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PMID:Heinz body production and hematological changes in the hen after administration of a single oral dose of n-butyl mercaptan and n-butyl disulfide. 687 30

Resistance to temephos, an organophosphorous insecticide (OP), was found to be low (2-fold) in 2 Culex pipiens populations collected in Sayada (mid-eastern Tunisia). This resistance was synergized by an esterase inhibitor (DEF). Two sets of over-produced esterases (A2-B2 and A4-B4), known to be involved in resistance, were identified in almost 50% of the examined insects. In addition, 3% of insects had an insensitive acetylcholinesterase. After selecting larvae of one of the samples (ES) with temephos for 6 generations, a 9-fold increase in resistance was observed, and all mosquitoes were found to carry esterases A2-B2 and an insensitive acetylcholinesterase. These results must be considered in future mosquito control programs, since 2 of the identified genes can lead to high resistance to several organophosphorous insecticides.
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PMID:Resistance to temephos, an organophosphorous insecticide, in Culex pipiens from Tunisia, North Africa. 750 77

The present review discusses the structure of the anticholinesterase organophosphates (OPs), which are used predominantly as insecticides. OP poisoning can occur in a variety of situations and can be accidental or suicidal. It is common in developing countries. The cholinergic syndrome is caused by acetylcholinesterase inhibition, and diagnosis is based on the clinical signs and symptoms as well as the measurement of inhibition of erythrocyte acetylcholinesterase and/or plasma cholinesterase activity. Antidotal treatment is with atropine, an enzyme reactivator such as pralidoxime and diazepam. Anticholinesterase OPs may produce effects other than the acute cholinergic syndrome, including the intermediate syndrome. Later effects may include organophosphorus-induced delayed neuropathy. Certain OPs are exploited for their anticholinesterase effects, including defoliants such as 'DEF', herbicides such as glyphosate, fire retardants and industrial intermediates. The toxicology of this group is heterogeneous and they may or may not possess anticholinesterase activity.
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PMID:Organophosphate poisoning. 841 73

Resistance to the organophosphates (OP) temephos, malathion, and pirimiphos methyl, and the carbamate propoxur was found to be low (< 5-fold) in 3 Aedes aegypti populations collected from Falcon and Aragua states of Venezuela. Resistance to chlorpyrifos (OP), permethrin, and lambda-cyhalothrin (pyrethroids) was moderate (7-fold) in both populations. Mechanisms of resistance were investigated with the synergists piperonyl butoxide (mixed function oxidase inhibitor) and S, S, S-tributyl phosphorothioate (DEF, an esterase inhibitor). Nonspecific esterase and oxidase enzymes played a significant role in OP and carbamate resistance, respectively. Resistance to pyrethroid insecticides was not affected by DEF or piperonyl butoxide. This suggested the presence of another mechanism such as altered target site sensitivity (kdr). Biochemical tests showed significantly greater amounts of esterase activity in field strains, whereas insensitive acetylcholinesterase was not involved in either OP or carbamate resistance. These results must be considered in future control programs for Ae. aegypti, because OPs and pyrethroids are currently used in vector control in most countries of Central and South America.
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PMID:Characterization of resistance to organophosphate, carbamate, and pyrethroid insecticides in field populations of Aedes aegypti from Venezuela. 855


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