Neurotoxic esterase inhibition

Padilla S, Veronesi B. 1985. The relationship between neurological damage and neurotoxic esterase inhibition in rats acutely exposed to tri-ortho-cresyl phosphate. Toxicol Appl Pharmacol 78 78-87. 

Veronesi, B., Padilla, S., andLyerly D., The correlation between neurotoxic esterase inhibition and mipafox-induced neuropathic damage in rats, Neurotoxicology, 7,207-15,1986. 

Ehrich, M., Neurotoxic esterase inhibition Predictor of potential for organophos-phate-induced delayed neuropathy. In Biomarkers for Agrochemicals and Toxic Substances. ACS Symposium Series 643, Blancato, J.N., Brown, R.N., Dary, C.C., andM.A. Saleh, Eds., Washington, DC, American Chemical Society, 79-93,1996. 

Clothier, B.. and Johnson, M. (1980). Reactivation and aging of neurotoxic esterase inhibited by a variety of organophospho-ru.s esters, Biochem. J. 18S, 739-747. 

Statistically or biologically significant changes in clinical or enzyme chemistry (e.g., neurotoxic esterase inhibition, cholinesterase inhibition, or peroxisome proliferation) are reportable. Statistically or biologically significant... 

Phosphonothioate Esters of Phenols. Phosphonates with a single P—C bond are highly toxic and persistent iasecticides but have not been used extensively because some compounds produce delayed neuropathy leading to irreversible paralysis ia higher animals, including humans. Such compounds specifically inhibit an enzyme, neurotoxic esterase, that is responsible for the growth and maintenance of long nerve axons (31,32). 

A third enzyme may have limited potential as a measure of exposure. Neurotoxic esterase, also known as neuropathy target esterase (NTE), is inhibited by certain organophosphate esters. When brain NTE is inhibited above 70% for acute or possibly as low as 50% for repeated exposures, there is a consensus that delayed neuropathy is likely. NTE also is found in lymphocytes and platelets (Lotti et al. 1984). The... 

Schwab BW, Richardson RJ. 1986. Lymphocyte and brain neurotoxic esterase Dose and time dependence of inhibition in the hen examined with three organophosphorus esters. Toxicol Appl Pharmacol 83 1-9. 

Some OP compounds induce delayed neurotoxic effects ("delayed neuropathy") after acute poisoning. This delayed neurotoxic action is independent of cholinesterase inhibition but related to phosphorylation of a specific esterasic enzyme in the nervous tissue, called "neurotoxic esterase" or "neuropathy target esterase" (NTE) (Johnson, 1982). NTE is present in the nervous tissue, liver lymphocytes, platelets, and other tissues, but its physiological function is unknown. There is a rather large inter-individual variation of lymphocyte and platelet NTE activity (Table 2). 

Online file. Environmental Criteria and Assessment Office, Office of Health and Environmental Assessment, Cincinnati, OH. Vranken, M.A., H.C. DeBisschop, J.L. Willems. 1982. In vitro inhibition of neurotoxic esterase by organophosphorus nerve agents. Arch. Int. Pharmacodyn. Ther. 260 316-318. (Cited in Munro et al., 1994)... 

Clothier, B., Johnson, M.K. (1979). Rapid aging of neurotoxic esterase after inhibition by di-isopropylphosphorofluoridate. Biochem. J. 177 549-58. 

Davis, S.L., Tanaka, D., Jr., Aulerich, R.J., Bursian, S.J. (1999). Organophosphorus-induced neurotoxicity in the absence of neuropathy target esterase inhibition the effects of triphenyl phosphine in the European ferret. Toxicol. Sci. 49 78-85. 

Padilla, S.S., Grizzle, T.G., Lyerly, D. (1987). Triphenyl phosphite in vivo and in vitro inhibition of rat neurotoxic esterase. Toxicol. Appl. Pharmacol. 87 249-56. 

Ehrich M, Correll L, Veronesi B. Acetylcholinesterase and neuropathy target esterase inhibitions in neuroblastoma cells to distinguish organophosphorus compounds causing acute and delayed neurotoxicity. Fund Appl Toxicol. 1997 38 55-63. 

See also A-Esterases Carbamate Pesticides Choiin-esterase inhibition Neurotoxicity Pesticides. 

TOCP produces a delayed neurotoxicity, by inhibiting a nonspecific neuronal carboxylesterase, neuropathic target esterase. The neuropathic target esterase appears to have a role in neuronal lipid metabolism. Neuropathic target esterase enzymatic activity is highest in nervous tissue. 

The complete mechanism of OPIDN has not been elucidated. However, there is good evidence that the disease is initiated by a concerted two-step reaction involving inhibition and aging of a critical amount of a protein called neuropathy target esterase (neurotoxic esterase, NTE) in target neural tissues. The net result of the aging step is the rapid formation of a... 

Pesticide assessment guidelines under the Federal Insecticide, Fungicide, and Rodenticide Act stipulate that organophosphates proposed for use as insecticides be tested both for their capability to cause acute toxicities due to inhibition of acetylcholinesterase and for their potential to cause inhibition of neurotoxic esterase and subsequent delayed neuropathy. Testing could be performed in laboratory rodents because they, like all species, are susceptible to acetylcholinesterase inhibition, but rodents do not develop notable ataxia, and neuropathological... 

Richardson, R. J., Moore, T.B., Kayyali, U.S., Fowke, J.H., and Randall, J.C. Inhibition of hen brain acetylcholinesterase and neurotoxic esterase by chlorpyrifos in vivo and kinetics of inhibition by chlorpyrifos oxon in vitro. Application to assessment of neuropathic risk, Fundam. Appl. Toxicol. 20,273-279,1993. 

The esterase got the names neurotoxic esterase or neuropathy target esterase, and the ester phenyl valerate (PV) was found to be a good substrate for this esterase. However, PV is also hydrolyzed by other esterases because paraoxon, which does not give symptoms of delayed neurotoxicity, inhibited the PV activity as much as 80%. The NTE is defined as the hydrolytic activity against PV that is not inhibited by paraoxon but by mipafox. About 3% of the activity is not inhibited by mipafox plus paraoxon. Thus, the part of PV activity due to neurotoxic esterase should be 17%. 

Johnson, M.K. and Loth, M. 1980. Delayed neurotoxicity caused by chronic feeding of organophosphates requires a high-point of inhibition of neurotoxic esterase. Toxicol. Lett., 5, 99-102. 

---