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

Abstract

Neuropathy target esterase (NTE) is the target protein for neuropathic organophosphorus (OP) compounds that produce OP compound-induced delayed neurotoxicity (OPIDN). Inhibition/aging of brain NTE within hours of exposure predicts the potential for development of OPIDN in susceptible animal models. Lymphocyte NTE has also found limited use as a biomarker of human exposure to neuropathic OP compounds. Recently, a highly sensitive biosensor was developed for NTE activity using a tyrosinase carbon-paste electrode for amperometric detection of phenol produced by hydrolysis of the substrate, phenyl valerate. The I₅₀ (20 min at 37°C) for N,N′-di-2-propylphosphorodiamid ofluoridate (mipafox) against hen lymphocyte NTE was 6.94 ± 0.28 μM amperometrically and 6.02 ± 0.71 μM colorimetrically. For O,O-di-1-propyl O-2,2-dichlorvinyl phosphate (PrDChVP), the I₅₀ against hen brain NTE was 39 ±8 nM amperometrically and 42 ±2 nM colorimetrically. The biosensor enables NTE to be assayed in whole blood, whereas this cannot be done with the usual colorimetric method. Amperometrically, I₅₀ values for PrDChVP against hen and human blood NTE were 66 ±3 and 70 ± 14nM, respectively. To study the possibility of using blood NTE inhibition as a biochemical marker of neuropathic OP compound exposure, NTE activities in brain and lymphocytes as well in brain and blood were measured 24 h after dosing hens with PrDChVP. Brain, lymphocyte, and blood NTE were inhibited in a dose-responsive manner, and NTE inhibition was highy correlated between brain and lymphocyte (r=.994) and between brain and blood (r=.997). The results suggest that the biosensor NTE assay for whole blood could serve as a biomarker of exposure to neuropathic OP compounds as well as a predictor of OPIDN and an adjunct to its early diagnosis.