Inhibition of lymphocytic neuropathy target esterase predicts the development of organophosphate-induced delayed polyneuropathy

Abstract

Neuropathy Target Esterase (NTE) is the molecular target in the nervous system for organophosphorus esters (OP) when they cause delayed polyneuropathy. Some NTE activity was recently found also in blood lymphocytes. An unsuccessful suicide attempt with the widely used pesticide chlorpyrifos (0,0-diethyl-0-3,5,6,-trichloro-2-pyridyl phosphorothioate) is reported, where prior inhibition of lymphocytic NTE correlates with the delayed development of polyneuropathy. A 42-year-old man drank approximately 300 mg/kg chlorpyrifos. The subsequent severe cholinergic syndrome lasted for 17 days with varying degrees of severity. Thirty days after intoxication the clinical and electrophysiological examination of the peripheral nervous system was normal but lymphocytic NTE was about 60% inhibited. On day 43 the patient began to complain of paresthesia and leg weakness. Clinical examination, electrophysiology and a nerve biopsy revealed signs of a peripheral polyneuropathy, axonal in type. This case report indicates that measurement of lymphocytic NTE might be used as a clinical test to predict the development of OP-induced delayed polyneuropathy.

Relative Inhibitory Potencies of Chlorpyrifos Oxon, Chlorpyrifos Methyl Oxon, and Mipafox for Acetylcholinesterase Versus Neuropathy Target Esterase

“…Using kinetic determinations of k i values obtained from linear kinetics, the corresponding RIP was found to be 107 (Richardson et al, 1993). In either case, it is clear that the RIP of CPO is >>1, indicating that CPS could not produce OPIDN at sublethal doses, consistent with experimental results in animals (Capodicasa et al, 1991;Richardson et al, 1993) and clinical data on humans (Lotti et al, 1986;Moretto & Lotti, 1998).…”

Lysophosphatidylcholine hydrolases of human erythrocytes, lymphocytes, and brain: Sensitive targets of conserved specificity for organophosphorus delayed neurotoxicants

“…NTE is a contributor to brain LysoPC hydrolyzing activity (Quistad and Casida, 2004). NTE is found in lymphocytes (Lotti et al, 1986), but the blood enzymes responsible for LysoPC hydrolytic activity are not identified. Although LysoPLAs and NTE hydrolyze the same LysoPC substrate, they are not homologous enzymes.…”

“…1). Lymphocyte NTE inhibition assayed with PV has been proposed to monitor exposure to insecticides and OPIDN agents (Lotti et al, 1986), but this approach has limited value due to poor enzyme stability and reproducibility (Lotti, 1992;Mutch et al, 1992). Erythrocyte and lymphocyte LysoPC hydrolases are possible alternative biomarkers for OP delayed neurotoxicant exposure.…”

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

“…Inhibition of brain NTE within hours of exposure to a neuropathic OP compound predicts the potential for OPIDN to appear in susceptible animal models (e.g., adult hens) after a delay of 1 to 3 wk. NTE has also been found in circulating lymphocytes and platelets (Bertoncin etal., 1985;Dudek & Richardson, 1982;Maroni & Bleecker, 1986;Richardson & Dudek, 1983), and lymphocyte NTE has been used or proposed for use as an accessible biomarker of animal and human exposure to neuropathic OP compounds (Johnson, 1990;Lotti, 1986;Lotti et al, 1983Lotti et al, , 1986Richardson & Dudek, 1983;Schwab & Richardson, 1986). Furthermore, lymphocyte NTE inhibition has been suggested as a predictor of OPIDN or an adjunct for its early diagnosis (Ehrich, 1996;Lotti, 1987;Mutch et al, 1992;Richardson & Dudek, 1983;Wilson & Henderson, 1992).…”