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:3.1.1.8 (cholinesterase)
12,691 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chicken spinal cord adenosine triphosphatases (both Na+, K+ stimulated and ouabain insensitive) were inhibited by tri-o-tolyl phosphate (TOTP, a neurotoxic organophosphate which is not a cholinesterase inhibitor) and mevinphos (a non-neurotoxic compound but inhibitor of cholinesterases). The inhibition was concentration and time dependent, with an initial rapid drop in activity followed by a gradual exponential decline.
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PMID:Synaptosomal adenosine triphosphatase (ATPase) inhibition by organophosphates. 13 20

Rodents are relatively insensitive to the neurotoxic effects of various organophosphorus compounds. The purpose of this investigation was to determine if differences in inactivation of CBDP could explain the strain differences in the sensitivity to neurotoxicity following administration of TOCP (tri-o-cresyl phosphate) observed by Carrington and Abou-Donia (1988). Serum carboxylesterase but not cholinesterase is an important detoxification route for organophosphates. Serum carboxylesterase and cholinesterase activity were significantly different (p less than 0.05) among the various strains of rats. The rank order of carboxylesterase activity was Sprague Dawley (6158 nmole/ml serum/min) greater than Long Evans (5589) greater than Fischer 344 (5010) whereas the rank order for cholinesterase activity was Fischer 344 greater than Sprague Dawley greater than Long Evans. TOCP is metabolized to the active neurotoxicant CBDP (2-/o-cresyl/4H:1:3:2-benzodioxaphosphorin-2-oxide). The ED50 for CBDP inhibition of serum carboxylesterase activity was found to vary considerably for the various strains of rats. The rank order of CBDP ED50 concentration in the various strains was Fischer 344 (437 microM) greater than Long Evans (339 microM) greater than Sprague Dawley (78 microM), indicating that there was a difference between the carboxylesterase of the various strains with regard to interaction with CBDP. It is suggested that the differences in the quantity of serum carboxylesterase combined with the differences in the interaction of the inhibitor with the enzyme(s) may be responsible for the strain differences observed by Carrington and Abou-Donia (1988).
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PMID:Serum carboxylesterase activity in various strains of rats: sensitivity to inhibition by CBDP (2-/o-cresyl/4H:1:3:2-benzodioxaphosphorin-2-oxide). 240 90

The neurotoxicities of single doses of a chemical warfare agent VX [phosphonothioic acid, methyl-S-(2-[bis(1-methylethyl)amino/ethyl) O-ethyl ester], a metabolite of the agricultural chemical parathion, paraoxon, PO (phosphonothioic acid, diethyl paranitrophenyl ester), and the known neuropathic agents DFP] phosphorofluoridic acid, bis(1-methylethyl) ester] and TOCP (phosphoric acid, tri-o-tolyl ester) were compared in the chicken. Single injections (subcutaneous, sc) of VX as high as 150 micrograms/kg (5 times the LD50, intramuscular, im) were tolerated by laying tens if atropine and 2-pralidoxime were used as antidotes before and immediately after injection. The 150 of VX for inhibition of chicken brain acetylcholinesterase was approximately 5 X 10(-10). Plasma acetylcholinesterase, but not butyrylcholinesterase, was depressed 2 h after injections of 2-20 micrograms VX/kg im without antidotes. Levels of plasma enzymes such as creatine kinase, indicative of tissue damage, were increased after exposure to both VX and PO. Injections of up to 150 micrograms/kg of VX with antidotes did not cause locomotor or histological signs of organophosphorus-induced delayed neuropathy, but single injections of 400 mg TOCP/kg did.
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PMID:Toxicity of an acute dose of agent VX and other organophosphorus esters in the chicken. 333 55

The present study examined the effects of a glucocorticoid and a mineralocorticoid on organophosphorus-induced delayed neuropathy (OPIDN) as previous investigations have indicated that an endogenous steroid with both properties could alter this syndrome in chickens. The glucocorticoid triamcinolone and the mineralocorticoid deoxycorticosterone were provided in the diet beginning 1 day before and continuing 10 days after triortho-tolyl phosphate (TOTP, 360 mg/kg po), phenyl saligenin phosphate (PSP, 2.5 mg/kg im), and diisopropyl phosphorofluoridate (DFP, 1 mg/kg sc). In a manner similar to that seen with corticosterone, a low concentration (0.1 ppm) of triamcinolone reduced and a high concentration (10 ppm) exacerbated clinical signs. Concentrations of deoxycorticosterone under 80 ppm also partially delayed or ameliorated ataxia induced by TOTP, PSP, and DFP, but a combination of 0.1 ppm triamcinolone and 80 ppm deoxycorticosterone was not more effective than triamcinolone alone. Peripheral nerve damage was noted in all chickens given organophosphorus compounds, whether or not they had been given corticoids. Both steroids induced hydroxylase activity, but effects on most other enzyme systems examined were unremarkable. High concentrations of triamcinolone (10 ppm) could, however, also reduce liver cytochrome P450 levels and liver cholinesterase activity. Exacerbation of OPIDN was most notable in chickens under highest stress, as indicated by elevated heterophil-to-lymphocyte ratios. The clinical, pathological, biochemical, and hematological indices of exposure to adrenocorticoids and agents inducing OPIDN in chickens were, therefore, similar for both a synthetic glucocorticoid and the endogenous steroid corticosterone.
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PMID:Types of adrenocorticoids and their effect on organophosphorus-induced delayed neuropathy in chickens. 334 Oct 34

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

A method for administration of highly toxic chemicals by inhalation was developed. The model has three features of special interest: (1) a diffusion cell for producing a constant gas concentration, if necessary for several hours and days, (2) a small rapidly equilibrated inhalation chamber (1100 ml), and (3) complete isolation of the toxic chemicals from the atmosphere. The LCt50 of the anticholinesterase soman [o-(1,2,2 trimethylpropyl)-methyl-phosphonofluoridate] was 400 mg min/m3, registered 24 hr after the end of exposure. The lethal concentration X time of soman was 520 +/- 60 mg min/m3 when exposing the animals until death in the inhalation chamber. The exposure was less than 30 min and the concentration of soman was 21 mg/m3. The inhibition of acetylcholinesterase, cholinesterase, and carboxylesterase activities in different tissues was analyzed to study the possible barrier mechanisms that might exist in the body to soman. There was a large inhibition of the carboxylesterase and cholinesterase activities in bronchi and lungs as well as in blood. Carboxylesterases were important as detoxifying enzymes, as shown by 70% enhancement in toxicity of soman following sc pretreatment with TOCP (tri-ortho-cresyl-phosphate), a carboxylesterase inhibitor.
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PMID:A method for generating toxic vapors of soman: toxicity of soman by inhalation in rats. 403 97

Five organophosphorous insecticides: Leptophos, EPN, Cyanofenphos, trichloronate and salithion proved to cause irreversible ataxia not only to chicken but also to mice and sheep. TOCP was included as a reference. Cyanofenphos blocked the catecholamine B-receptor binding activity with 3H-norepinephrine at a level similar to that of the specific inhibitor propranolol in the mouse heart preparation. In the lamb heart preparation, the B-receptor was more sensitive to Leptophos, salithion and TOCP than to propranolol. The six compounds and their oxons were screened for their in-vitro inhibition to monamine oxidase (MAO), acetyl cholinesterase (AChE) and neurotoxic esterase (NTE) in the brain of either mouse, lamb or chicken. It is believed that their AChE inhibition stands for their acute toxicity, while NTE inhibition is responsible for their paralytic ataxia.
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PMID:Biochemical interaction of six OP delayed neurotoxicants with several neurotargets. 616 54

The potential of isopropyl triphenyl phosphate (ITP) to produce delayed neurotoxicity in hens was examined using several techniques. ITP contained O,O,O-triphenyl phosphate (24%), O-o-isopropylphenyl O,O-diphenyl phosphate (25%), O,O-diisopropyl-phenyl O-phenyl phosphate (20%), O-o, p-diisopropylphenyl O,O-diphenyl phosphate (18%) and O-p-isopropylphenyl O,O-diphenyl phosphate (6%). Hens treated twice, 3 wk apart, with doses of ITP as high as 11.7 g/kg showed no clinical signs of delayed neurotoxicity and only mild signs of general toxicity. Furthermore, none showed even subtle neurohistologic changes suggestive of delayed neurotoxicity. ITP produced dose-dependent inhibition of hen plasma cholinesterase and brain neurotoxic esterase (NTE). The study was continued because NTE inhibition has been shown to be a reliable predictor of organophosphates that produce delayed neurotoxicity. ITP was administered prior to tri-o-tolyl phosphate (TOCP) challenge in order to determine if it altered development of TOCP delayed neurotoxicity. ITP neither enhanced nor reduced the onset or severity of neurotoxicity produced by TOCP. The time-course for brain and spinal cord NTE inhibition by ITP and TOCP were compared and found to be different. The maximum brain NTE inhibition produced by ITP (doses up to 11.7 g/kg) was never complete (always less than 90%), and spinal cord NTE inhibition was significantly less than that produced in the brain. In contrast, brain and spinal cord inhibition produced by 500 mg TOCP/kg were equal and greater than 90%. This testing regimen showed that ITP produced an effect on NTE at the biochemical level without producing clinical or neurohistologic abnormalities in treated hens. Furthermore, this biochemical effect was qualitatively different than that produced by the delayed neurotoxicant TOCP.
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PMID:Assessment of the delayed neurotoxic potential of isopropyl triphenylphosphate using a nontraditional testing strategy. 652 Aug 87

Injection of sublethal doses of soman in guinea-pig and mouse subcutaneously every 3.5, 8, 12 or 24 hours led to cumulative LD50 doses which were markedly higher than the acute one. When animals were exposed every 24 hrs to half LD50 doses of soman, a majority of guinea-pigs but relatively few mice, survived a total exposure of 5-6 times the acute LD50 dose. Guinea-pig brain and diaphragm acetylcholinesterase activities declined steadily during the repeated soman exposure. Plasma cholinesterase activity was less than 10% 1 hr after soman injection, but was restored to 40-50% of control within 24 hrs. Liver aliesterase activity was not significantly inhibited by soman, whereas plasma aliesterase activity was 70% inhibited after 1 hr and restored to control level within 24 hrs. TOCP treatment of guinea-pig led to 3-fold increase in acute soman toxicity, and reduced their tolerance from more than 6 lD50 to 2.5 LD50 dose of soman. It is included that the recovery of plasma aliesterase and cholinesterase play an important part in the observed tolerance towards repeated soman treatment.
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PMID:Toxicity of soman after repetitive injection of sublethal doses in guinea-pig and mouse. 733 67


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