scholarly journals Investigation of the Esterase Status as a Complex Biomarker of Exposure to Organophosphorus Compounds

2018 ◽  
Vol 1 (3) ◽  
pp. e00028
Author(s):  
G.F. Makhaeva ◽  
E.V. Rudakova ◽  
R.J. Richardson
Keyword(s):  
Medical Treatment ◽  
Organophosphorus Compounds ◽  
Accurate Diagnosis ◽  
Neuropathy Target Esterase ◽  
Low Doses ◽  
Early Diagnostics ◽  
Biomarker Of Exposure ◽  
Delayed Neurotoxicity ◽  
Vital Component ◽  
Control Compound

Development of biomarkers of human exposures to organophosphorus compounds OPCs and their quantification is a vital component of a system of prediction and early diagnostics of OPC-induced diseases. Our study was focused on investigation of esterase status as a complex biomarker of exposure to OPCs and an aid in accurate diagnosis. We suggest that this complex biomarker should be more effective and informative than standard assays of plasma butyrylcholinesterase (BChE), erythrocyte acetylcholinesterase (RBC AChE), and lymphocyte neuropathy target esterase (NTE). It will help: 1) to assess an exposure as such and to confirm the nonexposure of individuals suspected to have been exposed; 2) to determine if the exposure was to agents expected to produce acute and/or delayed neurotoxicity; 3) to perform dosimetry of the exposure, which provides valuable information for medical treatment. To confirm this hypothesis, we have examined the changes in activity of blood AChE, NTE, BChE and carboxylesterase (CaE) 1 h after i.p. administration of increasing doses of three OPCs with different esterase profiles: the known neuropathic compound O,O-dipropyl-O-dichlorovinyl phosphate (C3H 7O)2P(O)OCH=CCl2 (diPr-DClVP) as the control compound and two model dialkylphosphates (C2H5O)2P(O)OCH(CF3)2 (diEt-PFP) and (C4H9O)2P(O)OCH(CF3)2 (diBu-PFP). The esterases assay was performed in hemolysed blood by spectrophotometric (AChE, BChE, CaE) and biosensor (NTE) methods. Analysis of the obtained dose-dependences for blood esterases inhibition showed that blood BChE and CaE were the most sensitive biomarkers, allowing detection of low doses. Inhibition of blood NTE and AChE can be used to assess the likelihood that an exposure to OPC would produce cholinergic and/or delayed neuropathic effects.

scholarly journals Neuropathy target esterase in mouse whole blood as a biomarker of exposure to neuropathic organophosphorus compounds

2016 ◽  
Vol 36 (11) ◽  
pp. 1468-1475 ◽  
Author(s):  
Galina F. Makhaeva ◽  
Elena V. Rudakova ◽  
Larisa V. Sigolaeva ◽  
Ilya N. Kurochkin ◽  
Rudy J. Richardson
Keyword(s):  
Whole Blood ◽  
Organophosphorus Compounds ◽  
Neuropathy Target Esterase ◽  
Biomarker Of Exposure

BIOSENSOR DETECTION OF NEUROPATHY TARGET ESTERASE IN WHOLE BLOOD AS A BIOMARKER OF EXPOSURE TO NEUROPATHIC ORGANOPHOSPHORUS COMPOUNDS

2003 ◽  
Vol 66 (7) ◽  
pp. 599-610 ◽  
Author(s):  
Galina F. Makhaeva ◽  
Larisa V. Sigolaeva ◽  
Lyudmila V. Zhuravleva ◽  
Arkady V. Eremenko ◽  
Ilya N. Kurochkin ◽  
...  
Keyword(s):  
Whole Blood ◽  
Organophosphorus Compounds ◽  
Neuropathy Target Esterase ◽  
Biomarker Of Exposure

scholarly journals Studies on the delayed neurotoxicity of organophosphorus compounds. III.

1985 ◽  
Vol 10 (2) ◽  
pp. 67-82 ◽  
Author(s):  
Hirotoshi ITOH ◽  
Hidemi KISHIDA ◽  
Eiko TAKEUCHI ◽  
Mamoru TADOKORO ◽  
Toshiyuki UCHIKOSHI ◽  
...  
Keyword(s):  
Organophosphorus Compounds ◽  
Delayed Neurotoxicity

Review : Neuropsychopathological changes by organophosphorus compounds — a review

1995 ◽  
Vol 14 (11) ◽  
pp. 857-864 ◽  
Author(s):  
P. Eyer
Keyword(s):  
Organophosphorus Compounds ◽  
Toxic Effects ◽  
Neuropathy Target Esterase ◽  
Neurological Sequelae ◽  
Visual Functions ◽  
Organophosphate Intoxication ◽  
Increasing Risk ◽  
Clinically Significant ◽  
High Doses

1 Available literature dealing with neuropsychopathologi cal changes after exposure to organophosphate insecti cides is reviewed. 2 Subacute neurological sequelae following acute organophosphate intoxication include the 'intermediate syndrome', probably a myopathy elicited by excess acetylcholine, and the 'organophosphate-induced delayed neuropathy' (OPIDN), which is caused by particularly neurotoxic organophosphates that inhibit neuropathy target esterase. 3 Long-term toxic effects affecting behaviour as well as mental and visual functions are occasionally observed after exposure to high doses of organophosphates with repeated acute, clinically significant intoxications. 4 The available data do not indicate that asymptomatic exposure to organophosphates is connected with an increasing risk of delayed or permanent neuro psychopathological effects.

Current Status of the Neurobiology of Alzheimer's Disease and the Importance of Early Diagnosis

2002 ◽  
Vol 8 (4) ◽  
pp. 596-597
Author(s):  
Edith V. Sullivan
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Longitudinal Study ◽  
Early Diagnosis ◽  
Medical Treatment ◽  
Accurate Diagnosis ◽  
Current Status ◽  
Age Related ◽  
Loss Of Dignity ◽  
Scientific Rationale

Alzheimer's disease—occurring upward of 15% of individuals age 65 and older—is the most prevalent age-related dementia. Since the late 1970s, neuropsychologists have been instrumental in identifying patterns of sparing and impairment of cognitive, sensory, and motor functions and rates of declines in selective functions. Anyone who has engaged in longitudinal study of AD and anyone of that large segment of the population with relatives suffering with AD has witnessed first-hand the relentless, irreversible demise of function and ultimate loss of dignity characteristic of AD's course. The approach of Scinto and Daffner's edited book, Early Diagnosis of Alzheimer's Disease, avoids rehashing the already established descriptions of AD and provides firm, scientific rationale for the meaningfulness of early and accurate diagnosis of AD despite its current dire prognosis and lack of effective medical treatment.

497 Early diagnostics of delayed neurotoxicity

2003 ◽  
Vol 144 ◽  
pp. s133-s134 ◽  
Author(s):  
O.A. Khodakovskaya ◽  
N.A. Vodolazskaya ◽  
L.D. Glukhova ◽  
S.I. Timofeeva ◽  
A.S. Polezina ◽  
...  
Keyword(s):  
Early Diagnostics ◽  
Delayed Neurotoxicity

scholarly journals Characterization of [3H]di-isopropyl phosphorofluoridate-binding proteins in hen brain. Rates of phosphorylation and sensitivity to neurotoxic and non-neurotoxic organophosphorus compounds

1985 ◽  
Vol 228 (3) ◽  
pp. 537-544 ◽  
Author(s):  
C D Carrington ◽  
M B Abou-Donia
Keyword(s):  
Organophosphorus Compound ◽  
Binding Proteins ◽  
Organophosphorus Compounds ◽  
Polyacrylamide Gel Electrophoresis ◽  
Sodium Dodecyl ◽  
Reaction Rates ◽  
Binding Activity ◽  
Binding Characteristics ◽  
Delayed Neurotoxicity ◽  
Neurotoxic Esterase

The experiments described in this paper were designed to isolate [3H]di-isopropyl phosphorofluoridate-binding proteins by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis for the purpose of characterizing and identifying potential initiation sites for organophosphorus-compound-induced delayed neurotoxicity. The major Paraoxon-insensitive Mipafox-sensitive binding protein (Mr 160 000) was found to be identical with one previously identified as neurotoxic esterase, an enzyme that has been proposed to be the target site for organophosphorus-compound-induced delayed neurotoxicity. However, two other binding proteins with suitable binding characteristics were also found in smaller amounts, one of which has not been detected previously. Di-isopropyl phosphorofluoridate was found to phosphorylate all three of these proteins at rates similar to the rate at which neurotoxic esterase is inhibited by di-isopropyl phosphorofluoridate. Varying the concentration of di-isopropyl phosphorofluoridate or the time of incubation produced similar increases in binding to each of the labelled proteins. This suggests that the reaction rates of di-isopropyl phosphorofluoridate with proteins may be described by first-order kinetics, and the concentration of the Michael is complex formed during binding is minimal for all the phosphorylated proteins. The recovery of the binding activity in the 160 000-Mr band was found to be similar to the recovery of neurotoxic esterase activity, lending further support to the contention that this band is identical with neurotoxic esterase.

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