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)

Organophosphorus compounds may induce oxidative stress leading to generation of free radicals and alterations in antioxidant and scavengers of oxygen free radicals. The present study demonstrates effect of acute exposure of dimethoate in causation of oxidative stress in male Wistar rats. Dimethoate was administered orally at doses 45, 75 and 90 mg/kg of body weight on the basis of LD(50) for 24 h. After administration of doses, the liver and brain homogenates were analyzed for various parameters of oxidative stress. The results indicated an increase in hepatic cytochrome P450, lipid peroxidation, catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase in liver and brain at 90 and 75 mg/kg doses. There were no significant changes in the levels of glucose-6-phosphate dehydrogenase activity in both liver and brain. Similarly, there were no significant changes in hepatic glutathione and glutathione-S-transferase activities. However, there was a significant increase in glutathione and glutathione-S-transferase in brain at 90 mg/kg dose only. Erythrocyte acetylcholinesterase was inhibited at all doses used. Dose-dependent histopathological changes, observed in both liver and brain, are also described.
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PMID:Effects of acute dimethoate administration on antioxidant status of liver and brain of experimental rats. 1559 Jan 8

The pulmonary epithelial lining fluid (ELF) contains substrates, e.g., ascorbic acid (AH2), uric acid (UA), glutathione (GSH), proteins, and unsaturated lipids, which undergo facile reaction with inhaled ozone (O3). Reactions near the ELF gas/liquid interface likely provide the driving force for O3 absorption ("reactive absorption") and constrain O3 diffusion to the underlying epithelium. To investigate the potential mechanisms wherein O3/ELF interactions may induce cellular damage, we utilized a red cell membrane (RCM) model intermittently covered by an aqueous film to mimic the lung surface compartmentation, and evaluated exposure-mediated loss of acetylcholinesterase activity (AChE) and TBARS accumulation. In the absence of aqueous reactants, O3 exposure induced no detectable changes in AChE or TBARS. AH2 and GSH preferentially induced oxidative damage in a dose-dependent fashion. AH2-mediated RCM oxidation was not inhibited by superoxide dismutase, catalase, mannitol, or Fe chelators. O3 reaction with UA, Trolox, or albumin produced no RCM oxidation but oxidation occurred when AH2 was combined with UA or albumin. Rat bronchoalveolar lavage fluid (BALF) also induced RCM oxidation. However, in vivo O3 exposure dampened the extent of BALF-mediated RCM oxidation. Although we cannot completely rule out O3 diffusion to the RCM, product(s) derived from O3 + AH2/GSH reactions (possibly O3*- or 1O2) likely initiated RCM oxidation and may suggest that in vivo, such secondary species account for O3 permeation through the ELF leading to cellular perturbations.
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PMID:Antioxidant-mediated augmentation of ozone-induced membrane oxidation. 1564 54

Marine mussels Mytilus sp. were transplanted on a monthly basis in cages over one year to oyster farms and harbours in the Arcachon Bay (France) in order to assess the water quality of the bay. Contaminant levels (organotin compounds, trace metals, PCBs and PAHs) were measured in tissues of transplanted mussels and mussels from a reference station, along with physiological parameters of the mussels (condition indexes, lipid content and dry weight). Four biomarkers (AChE: acetylcholinesterase activity, GST: gluthathione S-transferase activity, CAT: catalase activity and TBARS: thiobarbituric acid-reactive substance content) were also monitored. The remote stations monitored (oyster parks) exhibited no accumulation pattern of pollutants. Their respective concentrations therefore constitute a background level of the contamination in the bay ([TBT]= 30 ng Sn g(-1) dw, [SigmaHAPs]= 100 ng g(-1) dw, [SigmaPCBs]= 35 ng g(-1) dw). The elevated chemical contamination of the largest harbour of the bay, the Arcachon harbour, can be interpreted in terms of persistence of organotin compounds ([SigmaOTs]= 1500-2000 ng Sn g(-1) dw) and PAHs ([SigmaHAPs]= 4500-5000 ng g(-1) dw) in sediments and, to a lesser extent, of direct inputs of copper ([Cu]= 20 microg g(-1) dw in harbours versus 7 in oyster parks) and petrogenic PAHs ([methylphenanthrenes]= 1600 ng g(-1) dw in the dockyard versus 170 at the gas stations), related to the use of copper-based antifouling paints and to dockyard activity, respectively. However, the Arcachon Bay presents a low contamination level by PCBs and metals, including harbour stations. Furthermore, higher levels of other PAHs (particularly alkyl PAHs such as methylphenanthrenes/1600 ng g(-1) dw) not included in the 16 PAHs from the EPA priority list (usually studied in biomonitoring programmes/1500 ng g(-1) dw) in the Arcachon harbour underline the need to integrate these compounds in biomonitoring of highly PAH-polluted areas such as harbours in order to avoid misinterpretation of the biological responses observed. Biomarker responses were not able to discriminate the different chemical contamination levels recorded in the Arcachon Bay and rather reflected changes in environmental factors. Furthermore, the strong intraspecies variability of biological responses could be due to genetic differences of mussels from the Arcachon Bay. It is the first time that such an integrated monitoring is performed in the Arcachon Bay, also taking into account seasonal variations of chemical contents and biomarkers levels in mussel tissues.
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PMID:One-year monitoring survey of organic compounds (PAHs, PCBs, TBT), heavy metals and biomarkers in blue mussels from the Arcachon Bay, France. 1573 81

The aim was to apply a multimarker scoring approach as complementary to freshwater monitoring programmes carried out by the Water Agency Adour-Garonne. Fish (chub, barbel and trout) were collected in 11 sites in rivers in south-west France. Five biomarkers of response were measured either in muscle or brain for acetylcholinesterase (AChE) and in liver for glutathione S-transferase, catalase and 7-ethoxyresorufine O-deethylase. As a result of multivariate analysis, sites were clearly discriminated mainly by 7-ethoxyresorufine O-deethylase and acetylcholinesterase activities. According to the scoring approach, a multimarker pollution index was calculated for each sampling site as the sum of the response index of the five measured biomarkers (pollution index). Sorting was established by ranging the sites from lightly to highly contaminated locations.
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PMID:Scoring approach based on fish biomarkers applied to French river monitoring. 1576 91

The clam Ruditapes decussatus is distributed worldwide and due to its ecological and economical interest has been proposed as a bioindicator in areas where mussels are not available. The accumulation of several anthropogenic compounds in their tissues suggests that they possess mechanisms that allow them to cope with the toxic effects of these contaminants. Besides pollutant uptake, the use of biomarkers is pointed out in this paper since it is a promising approach to monitor the effect of these contaminants in the marine environment. Biomarkers complement the information of the direct chemical characterization of different types of contaminants. Therefore, the aim of this paper is to review the role of several biomarkers: (metallothioneins (MT), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidases (GPx) (total and selenium-dependent), lipid peroxidation (measured as MDA, one of the final products of lipid peroxidation), glutathione S-transferase (GST) and acetylcholinesterase (AChE), measured in different tissues of the clam R. decussatus, in laboratory conditions and under various environmental stresses, in two ecosystems (Ria Formosa lagoon- Portugal) and Bizerta lagoon (Tunisia) in a perspective of a multibiomarker approach to assess environmental changes. Experiment and field studies are in good agreement since MT levels, especially in the gills, the first target tissue of these contaminants, can be used as biomarker of exposure to Cd. GPx and MDA may also be determined in this respect. AChE activity is inhibited by pesticide and, to a less extent, by metal exposure in the gills and whole soft body of clams. However, the induction of GST isoforms experimentally demonstrated is not observed in the field because only global GST activity was determined. The whole set of results opens new research perspectives for the use of this species to assess the effect of mixtures of pollutants in the aquatic environment.
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PMID:Biomarkers in Ruditapes decussatus: a potential bioindicator species. 1576 95

We have developed a model system in which rat basal forebrain cholinergic neurons degenerate progressively when maintained in culture conditions that make them susceptible to low-level oxidative stress. In this study, we showed that cholinergic neurons identified by acetylcholinesterase cytochemistry or choline acetyl transferase immunocytochemistry are rescued efficiently by the neurotransmitter noradrenaline (NA). The effect of NA required neither adrenoceptor activation nor intracellular accumulation. NA operated via a mechanism that precluded activation of a cell death pathway in which reactive oxygen species (ROS) and proapoptotic caspases were crucially involved. It is noteworthy that NA remained protective even when applied late in the degenerative process but before intracellular ROS began to increase. The high efficacy of iron chelators and catalase in preventing the death of cholinergic neurons in this model suggested that NA neutralized the effects of hydroxyl radicals produced through a Fenton-type reaction. Pyrocatechol [the diphenolic moiety of NA] was sufficient in itself to prevent ROS production and cholinergic cell demise, indicating that the catechol structure was instrumental for the neuroprotective function of NA. Therefore, the noncatecholic neurotransmitter GABA failed to prevent neurodegeneration. Nerve growth factor and brain derived neurotrophic factor, two trophic peptides for septal cholinergic neurons, did not afford protection by themselves and did not improve neuroprotection provided by NA. However, in the presence of NA, they both retained their efficacy to stimulate cholinergic parameters. These data indicate that NA-based therapeutic strategies may be of interest in such neurodegenerative conditions as Alzheimer's disease, where progressive cholinergic deficits occur.
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PMID:The neurotransmitter noradrenaline rescues septal cholinergic neurons in culture from degeneration caused by low-level oxidative stress. 1578 47

In the present work we investigated the effect of ovariectomy on Na+, K+-ATPase and acetylcholinesterase (AChE) activities in rat hippocampus. We also studied some parameters of oxidative stress, namely total radical-trapping antioxidant potential (TRAP), thiobarbituric acid-reactive substances (TBA-RS), as well as the antioxidant enzyme activities superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities. Our hypothesis is that ovariectomy might cause alterations in essential enzyme activities necessary to brain normal functioning and that these chances could be caused by oxidative stress. Female adult Wistar rats were divided into three groups: (1) naive (control); (2) sham-operated; and (3) ovariectomized. Thirty days after ovariectomy rats were sacrificed. Results showed that rats subjected to ovariectomy presented a significant increase in Na+, K+-ATPase, AChE and CAT activities, but did not change the oxidative stress parameters studied when compared to sham or naive rats. Since ovariectomy mimics postmenopausal changes, our findings showing alteration in the activities of brain Na+, K+-ATPase, AChE and CAT may be related to problems in postmenopausal women.
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PMID:Ovariectomy increases Na+, K+-ATPase, acetylcholinesterase and catalase in rat hippocampus. 1586 39

Metallothionein level (MT), and acetylcholinesterase (AChE), catalase (CAT) and glutathione-S-transferase (GST) enzyme activities in the bivalves Mytilus edulis and Macoma balthica were investigated for seasonal variations from an inshore and an offshore site in the northern Baltic Sea. All the biomarkers showed variability, following mostly a similar pattern at both sites. Relationships between biomarkers and environmental factors and protein concentration and weight of target tissues were examined. In M. edulis, GST activity was related to Secchi depth, while in M. balthica a correlation with near-bottom oxygen saturation was observed. AChE activity correlated with the weight of the foot tissue of M. balthica. In both species, an integrated biomarker index indicated a stressed condition during the spring/early summer period. Strong seasonal variability in temperature and a concentrated period of food availability in spring-both governing the reproductive cycle of the bivalves-probably explains most of the observed natural variability in biomarkers in this sea area.
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PMID:Seasonal variability in biomarkers in the bivalves Mytilus edulis and Macoma balthica from the northern Baltic Sea. 1592 63

Organophosphate compounds act by irreversible inhibition of cholinesterase. In addition to their muscarinic, nicotinic, and central nervous system effects, some organophosphate insecticides cause oxidative stress by increasing lipid peroxidation in erythrocytes and by increasing levels of the enzymes superoxide dismutase and catalase. In this study, the effects of an antioxidant, N-acetylcysteine (NAC), in organophosphate poisoning were investigated. After obtaining Animal Ethics Committee approval, 16 male Wistar rats were divided into 2 groups. Following anesthesia, rats were tracheostomized and mechanically ventilated. Invasive hemodynamic monitoring was begun and all rats were injected with 70 mg/kg of dichlorvos (DDVP) intraperitoneally. The rats in group 1 received placebo intravenous 0.9% NaCl and the rats in group 2 received 150 mg/kg intravenous NAC. Blood samples were obtained before injection of DDVP and 60 minutes after injection to determine levels of malondialdehyde, superoxide dismutase, and catalase. Hemodynamic data and biochemistry test results were compared by analysis of variance and Wilcoxon test. P<.05 was regarded as statistically significant. Superoxide dismutase and malondialdehyde levels were significantly increased in group 1 while no difference was observed in group 2. It was concluded that organophosphate compounds might cause oxidative stress by interfering with antioxidant defense mechanisms in erythrocytes and that NAC might prevent increased lipid peroxidation. In addition to classic treatments, drugs with antioxidant effects might therefore be promising in the treatment of organophosphate poisoning.
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PMID:The effects of N-acetylcysteine on oxidative stress in organophosphate poisoning model. 1602 Apr 1

We tested a working hypothesis that stress genes and anti-oxidant enzyme machinery are induced by the organophosphate compound dichlorvos in a non-target organism. Third instar larvae of Drosophila melanogaster transgenic for hsp70 were exposed to 0.1 to 100.0 ppb dichlorvos and 5.0 mM CuSO(4) (an inducer of oxidative stress and stress genes) and hsp70, and activities of acetylcholinesterase (AchE), superoxide dismutase (SOD), catalase (CAT) and lipid peroxidation (LPO) product were measured. The study was further extended to examine tissue damage, if any, under such conditions. A concentration- and time-dependent increase in hsp70 and anti-oxidant enzymes was observed in the exposed organism as compared to control. A comparison of stress gene expression with SOD, CAT activities and LPO product under similar experimental conditions revealed that induction of hsp70 precedes the anti-oxidant enzyme activities in the exposed organism. Further, concomitant with a significant inhibition of AChE activity, significant induction of hsp70 was observed following chemical exposure. Mild tissue damage was observed in the larvae exposed to 10.0 ppb dichlorvos for 48 h when hsp70 expression reaches plateau. Dichlorvos at 0.1 ppb dietary concentration did not evoke significant hsp70 expression, anti-oxidant enzymes and LPO and AchE inhibition in the exposed organism, and thereby, was found to be non-hazardous to D. melanogaster. Conversely, 1.0 ppb of the test chemical stimulated a significant induction of hsp70 and anti-oxidant enzymes and significant inhibition of AchE; hence this concentration of test chemical was hazardous to the organism. The present study suggests that (a) both stress genes and anti-oxidant enzymes are stimulated as indices of cellular defense against xenobiotic hazard in D. melanogaster with hsp70 being proposed as first-tier bio-indicator of cellular hazard, (b) 0.1 ppb of the test chemical may be regarded as No Observed Adverse Effect Level (NOAEL), and 1.0 ppb dichlorvos as Low Observed Adverse Effect Level (LOAEL).
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PMID:Hazardous effect of organophosphate compound, dichlorvos in transgenic Drosophila melanogaster (hsp70-lacZ): induction of hsp70, anti-oxidant enzymes and inhibition of acetylcholinesterase. 1602 96


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