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

Abstract

The adult hen is the standard animal model for testing organophosphorus (OP) compounds for organophosphorus compound-induced delayed neurotoxicity (OPIDN). Recently, we developed a mouse model for biochemical assessment of the neuropathic potential of OP compounds based on brain neuropathy target esterase (NTE) and acetylcholinesterase (AChE) inhibition. We carried out the present work to further develop the mouse model by testing the hypothesis that whole blood NTE inhibition could be used as a biochemical marker for exposure to neuropathic OP compounds. Because brain NTE and AChE inhibition are biomarkers of OPIDN and acute cholinergic toxicity, respectively, we compared NTE and AChE 20-min IC50 values as well as ED50 values 1 h after single intraperitoneal (i.p.) injections of increasing doses of two neuropathic OP compounds that differed in acute toxicity potency. We found good agreement between the brain and blood for in vitro sensitivity of each enzyme as well for the ratios IC50 (AChE)/IC50 (NTE). Both OP compounds inhibited AChE and NTE in the mouse brain and blood dose-dependently, and brain and blood inhibitions in vivo were well correlated for each enzyme. For both OP compounds, the ratio ED50 (AChE)/ED50 (NTE) in blood corresponded to that in the brain despite the somewhat higher sensitivity of blood enzymes. Thus, our results indicate that mouse blood NTE could serve as a biomarker of exposure to neuropathic OP compounds. Moreover, the data suggest that relative inhibition of blood NTE and AChE provide a way to assess the likelihood that OP compound exposure in a susceptible species would produce cholinergic and/or delayed neuropathic effects. Copyright © 2016 John Wiley & Sons, Ltd.

Easy-Preparable Butyrylcholinesterase/Microgel Construct for Facilitated Organophosphate Biosensing

“…These enzymes include primary targets acetylcholinesterase (AChE, acute cholinergic toxicity) and neuropathy target esterase (NTE, delayed neuropathy), as well as secondary targets butyrylcholinesterase (BChE) and carboxylesterase (CaE), which act as scavengers of OPs, − whereas paraoxonase (PON1) can hydrolyze and detoxify OPs. Surveillance of living organisms exposed to cholinergic and neuropathic OPs depends on the toxicity of a specific OP, its dose, and the individual sensitivity to OPs …”

“…Surveillance of living organisms exposed to cholinergic and neuropathic OPs depends on the toxicity of a specific OP, its dose, and the individual sensitivity to OPs. 6 Defending against such agents requires rapid, sensitive, and specific detection as well as quantification of OPs in environmental matrices preferably before contact and following toxic exposure to humans. Enzymatic biosensors represent ideally suited prescreening tools for rapid and simple express analysis of OPs pollutants.…”

Human diseases associated with NTE gene

“…Фосфорорганические эфиры, такие как мипафокс, диизопропилфторфосфат, хлорофос, дихло фос, ингибируют как NTE, так и AchE, BchE [14,15] [17]. Позднее, активность NTE была обнаружена в лим фоцитах курицы [18], человека [19], мыши [20], что значительно упрощает скрининг OP на токсичность.…”

In Situ SERS Sensing by a Laser-Induced Aggregation of Silver Nanoparticles Templated on a Thermoresponsive Polymer

“…Thus, the hydrophilic–hydrophobic balance of PDMAEMA can be changed by varying both the pH and temperature. Linear PDMAEMAs and PDMAEMA-based diblock copolymers have been used as efficient surface modifiers for the design of various types of electrochemical sensors, e.g., for choline [ 25 , 26 , 27 ], phenol [ 28 ], myoglobin [ 29 ], dsDNA [ 30 , 31 ], and drugs [ 32 ], as well as to reveal drug–DNA interactions [ 33 ]. PDMAEMA-based (co/ter)polymers were applied for the non-viral delivery of genetic material into cells [ 34 , 35 ].…”