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)

The accepted mechanism of toxicity of many organophosphorous and carbamate insecticides is inhibition of acetylcholinesterase activity. In mammals, part of the toxicity assessment usually includes monitoring blood and/or brain acetylcholinesterase inhibition. Other tissues, however, contain cholinesterase activity (i.e. acetyl- and butyryl-cholinesterase), and the inhibition of that activity may be informative for a full appraisal of the toxicity profile. The present group of studies first optimized the variables for extraction and solubilization of cholinesterase activity from various rat tissues and then refined an existing automated method, in order to differentially assess acetyl and butyrylcholinesterase activity in those tissues. All these studies were conducted using tissues from untreated, Long-Evans, adult rats. The first studies determined the effect of Triton X-100 or salt (NaCl) on the extraction and solubilization of cholinesterase activity from retina, brain, striated muscle, diaphragm, and heart: phosphate buffer plus detergent (1% Triton X-100) yielded the highest activity for most tissues. For striated muscle, however, slightly more activity was extracted if the phosphate buffer contained both 1% Triton X-100 and 0.5 M NaCl. It was also noted that the degree of homogenization of some tissues (e.g. striated muscle) must be increased for maximal solubilization of all cholinesterase activity. Subsequent studies developed a method for assessing the level of acetylcholinesterase, butyrylcholinesterase and total cholinesterase activity in these tissues using an automated analyzer. In conclusion, automated assay of acetylcholinesterase activity in cholinergically innervated tissues in the rat (other than brain) is achievable and relatively convenient.
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PMID:Automated measurement of acetylcholinesterase activity in rat peripheral tissues. 1262 16

Per (3,6-anhydro-2-O-carboxymethyle) alpha-cyclodextrin ([ACX]) is a polydentate analog of EDTA, a well-known cation chelating reagent. ACX exhibits strong affinities in vitro for uranyl, cobalt and also for lanthanids such as Europium and Cerium. The hydrolytic activities of ACX-Eu and ACX-Ce complex were directly tested on an organophosphorous compound: the neurotoxic Soman (GD), an inhibitor of acetylcholinesterase (ACHE from rat brain). It was found a three fold reduction of soman activity when measured in the presence of Ce-ACX complex. Conversely, Eu-ACX effect did not result in soman inhibition variation under physiological conditions. It is suggested that, considering usual organometallic complex of cyclodextrin, such direct complexes would be of interest in the design of pseudo-enzyme systems for phosphoester hydrolysis.
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PMID:Hydrolytic properties of per (3,6-anhydro, 2-O-carboxymethyl) alpha cyclodextrin complexes of Ce (III) and Eu (III): application to soman (GD) degradation. 1280 27

Cadmium is a well-known human carcinogen and a potent nephrotoxin. Lipid peroxidation is involved in cadmium-related toxicity. Vitamin E and beta-carotene are effective antioxidants and free radical scavengers. Therefore, the present study was carried out to investigate the potential protective effects of vitamin E and beta-carotene alone or in combination against cadmium (Cd) toxicity. Cadmium chloride (CdCl2, 5 mg/kg BW, 1/15 LD50), vitamin E (100 mg/kg BW), beta-carotene (10 mg/kg BW), and vitamin E with beta-carotene (100 + 10 mg/kg BW, respectively) were orally administered by gavage alone or in combination. The tested doses were given to rats every other day (15 times). Results obtained showed that CdCl2 significantly (P < 0.05) induced free radicals in plasma, liver and brain. The activities of glutathione S-transferase (GST) (plasma and liver), alkaline phosphatase (AlP) (plasma and liver), aspartate aminotransferase (AST), alanine aminotransferase (ALT) (liver) and acetylcholinesterase (AChE) (plasma and brain) were significantly (P < 0.05) decreased due to CdCl2 administration, whereas, the activities of AST and ALT were increased in plasma. Treatment with CdCl2 caused a significant (P < 0.05) increase in glucose, urea, creatinine and bilirubin in plasma. On the other hand, results showed that CdCl2 significantly (P < 0.05) decreased plasma total protein (TP), albumin (A), blood hemoglobin (Hb), total erythrocytic count (TEC) and packed cell volume (PCV), while total leukocyte count (TLC) increased. Treatment with CdCl2 caused a significant (P < 0.05) decrease in sperm concentration, motility (%), weight of testes and epididymis, and increase in dead and abnormal sperm. Results demonstrated the beneficial influences of vitamin E, -carotene alone and/or in combination in reducing the harmful effects of CdCl2.
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PMID:Cadmium-induced changes in lipid peroxidation, blood hematology, biochemical parameters and semen quality of male rats: protective role of vitamin E and beta-carotene. 1530 3

Trahira (Hoplias malabaricus) used to investigate the effects of successive Pb(II) or tributyltin (TBT) dietary doses. After 70 days of acclimation, individuals were exposed to 21 microg Pbg(-1) or 0.3 microg TBTg(-1) (5-day intervals, 14 doses). Two experiments were conducted to investigate the histopathological effects (liver and kidney) and measure the cholinesterase activity (muscle and brain) after Pb(II) or TBT dietary doses. A number of morphological effects were observed in liver, including cytoskeleton disturbance, microautophagy of mitochondria, nuclear damage, and cell death. In kidney, necrosis area, increasing of the neutrophils cell number, changes in melano-macrophage centers, and free macrophages were frequently registered after both Pb(II) and TBT exposures. The cholinesterase activity was inhibited in muscle after 14 doses of Pb(II), but no effects were found in individuals exposed to TBT. In summary, this work is the first to report detailed in vivo toxic effects in tropical fish, H. malabaricus, after dietary sublethal exposure to Pb(II) and TBT.
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PMID:Effects of dietary Pb(II) and tributyltin on neotropical fish, Hoplias malabaricus: histopathological and biochemical findings. 1554 30

Thespesia populnea (Malvaceae) is a large tree found in the tropical regions and coastal forests of India. Various parts of T. populnea are found to possess useful medicinal properties, such as antifertility, antibacterial, anti-inflammatory, antioxidant, purgative and hepatoprotective activity. The present study was undertaken to investigate the effects of T. populnea bark on cognitive functions, total cholesterol levels and cholinesterase activity in mice. A total of 312 mice divided into 52 different groups were employed in the present investigation. The ethanolic extract of T. populnea (TPE) was administered orally in three doses (100, 200 and 400 mg/kg) for 7 successive days to different groups of young and aged mice. The learning and memory parameters were assessed using elevated plus maze and passive avoidance apparatus. TPE (200 and 400 mg/kg, p.o.) showed significant improvement in memory of young and aged mice. TPE also reversed the amnesia induced by scopolamine (0.4 mg/kg, i.p.) and diazepam (1 mg/kg, i.p.). Furthermore, TPE reduced significantly the central (brain) cholinesterase activity in mice. TPE exhibited a remarkable cholesterol lowering property comparable to simvastatin (a standard drug) in the present study. Furthermore, we observed that, T. populnea bark possessed a powerful memory enhancing activity in mice. Since diminished cholinergic transmission and increased cholesterol levels appear to be responsible for development of amyloid plaques and dementia in Alzheimer patients, TPE may prove to be a useful medicine on account of its multifarious beneficial effects, such as memory improving property, cholesterol lowering, anticholinesterase and anti-inflammatory activity. Therefore, T. populnea bark appears to be a promising candidate for improving memory and it would be worthwhile to explore the potential of this plant in the management of Alzheimer patients.
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PMID:Pharmacological actions of Thespesia populnea relevant to Alzheimer's disease. 1686 May 52

Prunus persica L. Batsch water extract (PPE) is a potent acetylcholinesterase (AChE) inhibitor screened for the treatment of Alzheimer's disease. The effects of oral administration of the PPE were examined with comparison of those of selective butyrylcholinesterase inhibitors of 9-amino-1,2,3,4-tetrahydroacridine hydrochloride (tacrine) and tetraidopropylpyrophosphoramide (iso-OMPA) and a selective AChE inhibitor, donepezil, on the cholinesterase activity in the brain and plasma of rats. After the sequential solvent fractionation of the methanol extract of P. persica L. Batsch, the highest inhibitory fraction was that of chloroform (75%). The concentration that was required for 50% enzyme inhibition (IC(50) value) was 5.6 microg/mL for the chloroform fraction. Oral administration of PPE or tacrine caused a dose-dependent inhibition of brain and plasma cholinesterase activities. The ID(50) values of these compounds for brain cholinesterase activity were 2.7 g/kg and 8.9 mg/kg, respectively. On the other hand, the ID(50) values for plasma cholinesterase activity were 18.6 g/kg and 27.5 mg/kg, respectively. Thus, the ratios of the ID(50) (plasma < brain) were 6.0 and 3.1, respectively. These results suggest that orally administered PPE satisfactorily penetrates into the brain and inhibits cholinesterase there and that PPE is a potent inhibitor of brain cholinesterase in comparison with plasma cholinesterase in vivo.
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PMID:Pharmacological characterization of orally active cholinesterase inhibitory activity of Prunus persica L. Batsch in rats. 1695 99

The Rybinsk Reservoir (Russia) is the largest artificial waterbody in Europe (4550 km2) and provides drinking water for population of the cities located along the coast line. Industrialization in Cherepovets at the northeastern portion of the reservoir, including one of the largest metallurgical facilities in Europe, has resulted in chemical contamination of the reservoir. The extent of polychlorinated biphenyls (PCB) contamination in bream liver, a common fish species, taken from six locations in the Rybinsk Reservoir and Volga River, and biochemical and morphometric biomarkers of fish health were investigated. Liver PCB concentrations ranged from non-detected to 3.4 microg/g wet wt of liver, with the greatest concentrations found in fish taken near the industrialized area in Sheksna Reach of Rybinsk Reservoir. The source of the bream contamination is the PCB pollution of bottom organisms and sediments conditioned with industrialization facilities of Cherepovets. The patterns of the PCB congeners in the livers of bream taken near Cherepovets were similar at all of the stations that were sampled around the reservoir and Volga River. Among the common fish health biomarkers used only liver total ChE activity and liver-somatic index in bream near Cherepovets can reflect environmental pollution. Other morphometric (FCF, Clark's condition factors, and spleen-somatic index) and biochemical (protein content and acetylcholinesterase activity in the brain) biomarkers related with fish health varied among locations, but were not correlated to the concentrations of PCBs in the bream livers.
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PMID:Chemical contamination of the Rybinsk Reservoir, northwest Russia: relationship between liver polychlorinated biphenyls (PCB) content and health indicators in bream (Abramis brama). 1709 18

The potency of newly developed oximes (K074, K075) and commonly used oximes (obidoxime, HI-6) to reactivate nerve agent-inhibited acetylcholinesterase was evaluated in rats poisoned with tabun or cyclosarin at a lethal dose corresponding to the LD50 value. In vivo determined percentage of reactivation of tabun-inhibited blood and brain acetylcholinesterase showed that obidoxime is the most efficacious reactivator of tabun-inhibited acetylcholinesterase among studied oximes in the peripheral compartment (blood) although the differences between obidoxime and newly developed oximes were not significant. On the other hand, one of the newly developed oximes (K074) seems to be a significantly more efficacious reactivator of tabun-inhibited acetylcholinesterase in the central compartment (brain) than the other studied oximes. In addition, the oxime HI-6 is unable to sufficiently reactivate tabun-inhibited acetylcholinesterase in rats. In vivo determined percentage of reactivation of cyclosarin-inhibited blood and brain acetylcholinesterase in poisoned rats showed that HI-6 is the most efficacious reactivator of cyclosarin-inhibited acetylcholinesterase among the studied oximes in the peripheral (blood) as well as central (brain) compartment although the differences between the oxime HI-6 and other tested oximes in the brain were not significant. Due to their reactivating effects, both newly developed K-oximes can be considered to be promising oximes for the antidotal treatment of acute tabun poisoning while the oximes HI-6 is still the most promising oxime for the treatment of acute cyclosarin poisonings due to its high potency in reactivating cyclosarin-inhibited acetylcholinesterase in the peripheral as well as central compartment.
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PMID:A comparison of reactivating efficacy of newly developed oximes (K074, K075) and currently available oximes (obidoxime, HI-6) in cyclosarin-and tabun-poisoned rats. 1767 11

The reactivating and therapeutic efficacy of two salts of the oxime HI-6 (dichloride and dimethanesulphonate) against chosen nerve agents (tabun, soman and cyclosarin) was compared in rats. The potency of both salts of HI-6 to decrease the acute toxicity of tabun, soman and cyclosarin was similar in nerve agent-poisoned rats. While the potency of HI-6 dichloride and HI-6 dimethanesulphonate to counteract acute toxic effects of tabun is rather low, both salts of HI-6 were able to decrease the acute toxicity of soman two times and acute toxicity of cyclosarin more than three times. The therapeutic efficacy of both salts of the oxime HI-6 corresponds to their reactivating potency. While the reactivating efficacy of HI-6 dichloride as well as HI-6 dimethanesulphonate against tabun was negligible, their potency to reactivate soman-inhibited acetylcholinesterase and cyclosarin-inhibited acetylcholinesterase in peripheral (blood) and central (brain) compartment was relatively high. HI-6 dichloride showed a somewhat higher potency to reactivate tabun-inhibited acetylcholinesterase in brain, and soman-inhibited acetylcholinesterase in blood and brain than HI-6 dimethanesulphonate but the differences were not significant. Thus, the replacement of dichloride anion by dimethanesulphonate anion in the oxime HI-6 does not influence the therapeutic and reactivating efficacy of the oxime HI-6 against nerve agents. In addition, the higher solubility and stability of HI-6 dimethanesulphonate in comparison with HI-6 dichloride makes it possible to increase the dose and thus, the effectiveness of the oxime HI-6 in the antidotal treatment of acute nerve agent poisonings.
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PMID:Comparison of reactivating and therapeutic efficacy of two salts of the oxime HI-6 against tabun, soman and cyclosarin in rats. 1791 Jun 16

The kinetics of the bioaccumulation of malathion (O,O-dimethyl phosphorodithioate of diethyl mercaptosuccinate) and the biological impact of exposure for tiger salamanders, Ambystoma tigrinum, were assessed through exposure to soil surface contaminated with 50 microg/cm(2) or 100 microg/cm(2 )malathion and ingestion of an earthworm exposed to soil contaminated with 200 microg/cm(2) malathion. Malathion and malaoxon burdens in salamanders sampled at different times after exposure(s) were measured by gas chromatography in four tissue/organ subgroups: liver, epaxial muscle, pooled viscera (except the liver and brain), and pooled avisceral carcass (muscle, skin, and bone). The total tiger salamander xenobiotic burdens were calculated from these data. The malathion/malaoxon burden 1 day after exposure was greatest in the avisceral carcass and 2 days after exposure was greatest in the viscera. Bioconcentration and bioaccumulation factors remained less than unity throughout the experiment and did not support the hypothesis of bioaccumulation of malathion in the tiger salamander. Biological impact was assessed with a colorimetric brain cholinesterase microassay. Brain cholinesterase activities in salamanders exposed to malathion-contaminated soil (50 microg/cm(2) or 100 microg/cm(2 )malathion) were suppressed approximately 50-65% and 90%, respectively, compared to unexposed controls. The exposed animals did not exhibit overt clinical signs of malathion toxicosis.
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PMID:Acute toxicity and tissue distributions of malathion in Ambystoma tigrinum. 1822 61


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