Species differences in the in vitro inhibition of brain acetylcholinesterase and carboxylesterase by mipafox, paraoxon, and soman

Chattopadhyay, Dipanjan; Dighe, S. K.; Nashikkar, A. B.; Dube, Dipak K.

doi:10.1016/0048-3575(86)90091-x

Cited by 17 publications

(8 citation statements)

References 23 publications

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“…Electric eel was more sensitive compared to human AChE for CPO, PMO and DZO, whereas the carbamates were less potent in electric eel AChE. Such species differences between birds, fishes and mammals, including rats, have also been demonstrated in earlier reports for brain AChE inhibition, particularly for oxon compounds and carbamates (Andersen et al 1977;Chattopadhyay et al 1986;Johnson and Wallace 1987;Murphy et al 1968;Qadri et al 1994). It has been hypothesised that differences in affinity and the rate of phosphorylation of AChE or differences in the steric arrangement in the active site can contribute to species differences, resulting in different IC 50 s and species sensitivity distributions dependent on the compound (Andersen et al 1977;Wang and Murphy 1982).…”

Section: Discussionsupporting

confidence: 66%

Acetylcholinesterase inhibition in electric eel and human donor blood: an in vitro approach to investigate interspecies differences and human variability in toxicodynamics

et al. 2020

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In chemical risk assessment, default uncertainty factors are used to account for interspecies and interindividual differences, and differences in toxicokinetics and toxicodynamics herein. However, these default factors come with little scientific support. Therefore, our aim was to develop an in vitro method, using acetylcholinesterase (AChE) inhibition as a proof of principle, to assess both interspecies and interindividual differences in toxicodynamics. Electric eel enzyme and human blood of 20 different donors (12 men/8 women) were exposed to eight different compounds (chlorpyrifos, chlorpyrifos-oxon, phosmet, phosmet-oxon, diazinon, diazinon-oxon, pirimicarb, rivastigmine) and inhibition of AChE was measured using the Ellman method. The organophosphate parent compounds, chlorpyrifos, phosmet and diazinon, did not show inhibition of AChE. All other compounds showed concentration-dependent inhibition of AChE, with IC50s in human blood ranging from 0.2–29 µM and IC20s ranging from 0.1–18 µM, indicating that AChE is inhibited at concentrations relevant to the in vivo human situation. The oxon analogues were more potent inhibitors of electric eel AChE compared to human AChE. The opposite was true for carbamates, pointing towards interspecies differences for AChE inhibition. Human interindividual variability was low and ranged from 5–25%, depending on the concentration. This study provides a reliable in vitro method for assessing human variability in AChE toxicodynamics. The data suggest that the default uncertainty factor of ~ 3.16 may overestimate human variability for this toxicity endpoint, implying that specific toxicodynamic-related adjustment factors can support quantitative in vitro to in vivo extrapolations that link kinetic and dynamic data to improve chemical risk assessment.

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Section: Discussionsupporting

confidence: 66%

Acetylcholinesterase inhibition in electric eel and human donor blood: an in vitro approach to investigate interspecies differences and human variability in toxicodynamics

et al. 2020

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“…Metabolic alteration of OP compounds in vivo would alter the toxicity compared with that expected from in vitro data. Amphibians are believed to be relatively resistant to acute OP intoxication compared with mammals and birds [16][17][18][19]. Our data support these results: most of the tested compounds did not show a strong correlation between in vivo and in vitro anticholinesterase effect.…”

Section: Discussionsupporting

confidence: 84%

“…Amphibians are believed to be relatively resistant to acute OP intoxication compared with mammals and birds [16][17][18][19]. Amphibians are believed to be relatively resistant to acute OP intoxication compared with mammals and birds [16][17][18][19].…”

Section: Discussionmentioning

confidence: 99%

In Vitro and in Vivo Acetylcholinesterase-Inhibiting Effect of New Classes of Organophosphorus Compounds

Özmen¹,

Şener²,

Mete³

et al. 1999

Environ Toxicol Chem

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Anticholinesterase properties of 14 new synthesized organophosphorus (OP) compounds and four of their starting substances were tested in vitro and in vivo using electric eel acetylcholinesterase (AChE) and Rana ridibunda (frog of lowland) tadpoles, respectively. Gusathion‐M® was used as a reference anti‐AChE agent. Acetylcholinesterase inhibition capacity of tested compounds was assayed for 30‐min period in vitro studies using electric eel AChE, of which 14 OP compounds inhibited enzyme activity more than 50% within 30 min, excluding Gusathion‐M. However, four of the compounds inhibited AChE less than 50% during the test period. On the other hand, 12 of the OPs did not bring about mortality, whereas six of the tested compounds were found to be lethal agents for R. ridibunda tadpoles, for which values of concentration causing 50% lethality ranged from 14.42 to 89.95 ppm. Also, the highest degree of enzyme inhibition occurred by diethyl chlorophosphate (ETCP), which inhibited AChE activity 62% at 2.89 ppm in 24‐h toxicity tests and which was more effective than Gusathion‐M. The lethal OP compounds represented good correlation between dose and enzyme‐inhibition capability in in vivo tests, but only ETCP showed such a relation for anti‐AChE effect in both in vitro and in vivo conditions.

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“…Species‐related differences in the inhibition capacity of brain AChE by OP compounds that were closely related to the susceptibility of the species to OP poisoning were shown in previous studies. For example, AChE inhibition related to the toxicity of mipafox, paraoxon, somon, tabun, sarin, dimethylphosphorylfluoride, and diethylphosphorylfluoride were higher in chickens and in rats than in frogs (Andersen et al, ; Chattopadhyay et al, ). Wang and Murphy () also showed that chicken brain AChE was 100‐fold more sensitive to inhibition by methyl paraoxon than frog brain AChE.…”

Section: Discussionmentioning

confidence: 99%

Comparative assessment of in vitro and in vivo toxicity of azinphos methyl and its commercial formulation

Güngördü

Uçkun

2014

Environmental Toxicology

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The toxic effects of Gusathion (GUS), which is a commercial organophosphate (OP) pesticide, and also its active ingredient, azinphos methyl (AzM), are evaluated comparatively with in vitro and in vivo studies. Initially, the 96-h LC50 values of AzM and GUS were estimated for two different life stages of Xenopus laevis, embryos, and tadpoles. The actual AzM concentrations in exposure media were monitored by high-performance liquid chromatography. Also, the sub-lethal effects of these compounds to tadpoles were determined 24 h later at exposure concentrations of 0.1 and 1 mg/L using selected biomarker enzymes such as acetylcholinesterase (AChE), carboxylesterase (CaE), glutathione S-transferase (GST), glutathione reductase, lactate dehydrogenase, and aspartate aminotrasferase. Differences in AChE inhibition capacities of AzM and GUS were evaluated under in vitro conditions between frogs and fish in the second part of this study. The AChE activities in a pure electrical eel AChE solution and in brain homogenates of adult Cyprinus carpio, Pelophylax ridibundus, and X. laevis were assayed after in vitro exposure to 0.05, 0.5, 5, and 50 mg/L concentrations of AzM and GUS. According to in vivo studies AChE, CaE and GST are important biomarkers of the effect of OP exposure while CaE may be more effective in short-term, low-concentration exposures. The results of in vitro studies showed that amphibian brain AChEs were relatively more resistant to OP exposure than fish AChEs. The resistance may be the cause of the lower toxicity/lethality of OP compounds to amphibians than to fish.

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Species differences in the in vitro inhibition of brain acetylcholinesterase and carboxylesterase by mipafox, paraoxon, and soman

Cited by 17 publications

References 23 publications

Acetylcholinesterase inhibition in electric eel and human donor blood: an in vitro approach to investigate interspecies differences and human variability in toxicodynamics

Acetylcholinesterase inhibition in electric eel and human donor blood: an in vitro approach to investigate interspecies differences and human variability in toxicodynamics

In Vitro and in Vivo Acetylcholinesterase-Inhibiting Effect of New Classes of Organophosphorus Compounds

Comparative assessment of in vitro and in vivo toxicity of azinphos methyl and its commercial formulation

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