Biosensor Detection of Neuropathy Target Esterase in Whole Blood as a Biomarker of Exposure to Neuropathic Organophosphorus Compounds

摘要

Neuropathy target esterase (NTE) is the target for neuropathic organophosphonts compounds (OPs) that produce delayed neurotoxicity (OPIDN). Inhibition/aging of brain NTE predicts the potential for OPIDN in animal models. Lymphocyte NTE has also found use as a biomarker of human exposure to neuropathic OPs. Recently, a sensitive NTE biosensor was developed using a tyrosinase carbon-paste electrode for amperometric (Amp) detection of phenol produced by hydrolysis of the substrate, phenyl valerate. The I50 (20 min at 37 deg C) for N,N'-di-2 propylphosphorodiamidofiuoridate (mipafox) against hen lymphocyte NTE was 6.94 plus or minus 0.28 uM (Amp) and 6.02 plus or minus 0.71 uM colorimetrically (Col). For O.O-di-l-propyl O-2,2 -dichlorvinyl phosphate (PrDChVP), the I50 against hen brain NTE was 39 plus or minus 8 nM (Amp) and 42 plus or minus 2 nM (Col). I50 values (Amp) for PrDChVP against hen and human blood NTE were 66 plus or minus 3 and 70 plus or minus 14 nM, respectively. NTE activities in brain, lymphocytes. and blood were measured 24 h after dosing hens with PrDChVP. NTE inhibition was highly correlated between brain and lymphocyte (r=0.994) and brain and blood (r=0.997). Biosensor NTE assay for whole blood could serve as a biomarker of exposure to neuropathic OPs.