Pulmonary delivery of an aerosolized recombinant human butyrylcholinesterase pretreatment protects against aerosolized paraoxon in macaques
Yvonne J. RosenbergBeth L. LaubeLingjun MaoXiaoming JiangSegundo Hernandez-AbantoKeunmyoung D. LeeRobert J. Adams
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Butyrylcholinesterase
Paraoxon
Cholinesterase
Aerosolization
Alzheimer's disease (AD) is a progressive neurodegenerative disease characterised by low levels of the neurotransmitter (acetylcholine), oxidative stress, and inflammation of the central nervous system. The only currently available form of treatment entails the administration of AChE/BChE (acetylcholinesterase/butyrylcholinesterase) inhibitors to patients diagnosed with the disease. However, AD prevention is possible by administering the correct inhibitors with food. The aim of this study was to examine 19 types of honey in terms of their contents of cholinesterase inhibitors. The inhibition of AChE and BChE relative to the respective honey samples was evaluated using Ellman's colorimetric method, including the "false-positive" effect. The highest potential for AChE inhibition was observed in the case of thyme honey (21.17% inhibition), while goldenrod honey showed the highest capacity for BChE inhibition (33.89%). Our study showed that honeys may provide a rich source of cholinesterase inhibitors and, in this way, play a significant role in AD.
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Chagas Disease
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ABSTRACT Current methods for measuring acetylcholinesterase (AChE) activities in whole blood use butyrylcholinesterase (BChE)‐selective inhibitors. However, the poor selectivity of these inhibitors results in the inhibition of AChE activity to some degree, leading to errors in reported values. The goal of this study was to develop and validate a simple assay for measuring AChE and BChE activities in whole blood from humans as well as experimental animals. Blood was fractionated into plasma and erythrocytes, and cholinesterase activities were titrated against ethopropazine and (−)‐huperzine A to determine the lowest concentration of ethopropazine that inhibited BChE completely without affecting AChE activity and the lowest concentration of (−)‐huperzine A that inhibited AChE completely without interfering with BChE activity. Results indicate that 20 µ m ethopropazine can be successfully used for the accurate measurement of AChE activity in blood from humans as well as animals. Use of (−)‐huperzine A is not required for measuring BChE activity in normal or ‘exposed’ blood samples. The method was validated for blood from several animal species, including mice, rats, guinea pigs, dogs, minipigs, and African green, cynomolgus and rhesus monkeys. This method is superior to all reported methods, does not require the separation of erythrocyte and plasma fractions, and is suitable for measuring cholinesterase activities in fresh or frozen blood from animals that were exposed to nerve agents or those that were administered high doses of BChE. The method is simple, direct, reproducible, and reliable and can easily be adapted for high‐throughput screening of blood samples. Published 2012. This article is a US Government work and is in the public domain in the USA.
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Paraoxon
Butyrylcholinesterase
Pralidoxime
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The cholinesterases (acetylcholinesterase and butyrylcholinesterase)In this chapter, cholinesterase will be used to refer to both enzymes together (i.e., total cholinesterase), whereas acetylcholinesterase or butyrylcholinesterase will be used when referring to the specific esterase.
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18 alkaloids were successfully isolated from five Fritillaria species and 5 derivatives were synthesized. Their effects on the bioactivity of human whole blood cholinesterase (ChE) were assessed. The results showed that N-demethylpuqietinone, hupeheninoside, ebeiedinone, yibeinoside A and chuanbeinone inhibited the bioactivity of human whole blood ChE at the concentration of 1.0 × 10 - 4 M, with the inhibitory effects of 55.5 ± 2.7 %, 66.8 ± 2.0 %, 69.0 ± 1.7 %, 71.2 ± 1.8 % and 70.7 ± 3.3 %, respectively. The effects of the five alkaloids on human red blood cell (RBC) acetylcholinesterase (AChE) and human plasma butyrylcholinesterase (BChE) were further studied, and their IC50 values for human RBC AChE were 6.4 ± 0.003 μM, 16.9 ± 0.018 μM, 5.7 ± 0.004 μM, 6.5 ± 0.013 μM and 7.7 ± 0.001 μM, respectively, and the IC50 values for human plasma BChE were 12.5 ± 0.026 μM, 2.1 ± 0.005 μM, 5.2 ± 0.002 μM, 7.3 ± 0.005 μM and 0.7 ± 0.001 μM, respectively. These data suggest, therefore, that N-demethylpuqietinone, hupeheninoside, ebeiedinone, yibeinoside A and chuanbeinone have both anti-RBC AChE and anti-plasma BChE activities, N-demethylpuqietinone is a selective inhibitor of AChE, whereas hupeheninoside and chuanbeinone are the selective inhibitors of BChE.
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Objective To study activity of acetylcholinesterase(AChE)and butyrylcholinesterase(BuChE)in rat serum at different time points after repeated exposure to chlorpyrifos(CPF);to analyze relationship of the activity of AChE and BuChE. Methods 60female adult SD rats were randomly divided into 5groups by weight,12rats in each group:4chlorpyrifos dose groups(dosage:2.50、5.00、10.00、20.00mg/kg)and 1control group.Rats in all groups were successively treated with CPF for 10days by gavage.Blood samples of 3rats in each group were collected at 2nd,4th,7th and 11th d,activity of AChE and BuChE was determined.Results Serum AChE and BuChE activity decreased upon prolonged exposure time or when chlorpyrifos dosage increased in a dose-dependent manner.Activity of AChE and BuChE in serum showed a positive correlation(r= 0.872,P0.01),with similar trend upon repeated exposure.However,BuChE demonstrated greater inhibition effect compared to AChE(P0.01).Conclusion Inhibition of AChE and BuChE increased upon 10drepeated exposure to CPF.Serum BuChE can be considered as a sensitive indicator for organophosphorus pesticide exposure.
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Paraoxon
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The development of antidotes to organophosphate poisons is an important aspect of modern pharmacology. Recombinant acetylcholinesterase and butyrylcholinesterase are effective DNA-encoded acceptors of organophosphate poisons and, in particular, pesticides. Here, we present the results of a study on the effectiveness of recombinant butyrylcholinesterase (BChE) in modeling organophosphate poisoning caused by oral administration of paraoxon at a dose of 2 mg / kg. The study showed a high activity of BChE as a protective agent for subchronic anticholinesterase poisoning in an in vivo model. The administration of BChE in a dose of 20 mg / kg allows one to avoid mortality, and also contributed to rapid recovery after model poisoning.
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Paraoxon
Organophosphate poisoning
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