Neuropathy target esterase

A few OP compounds cause delayed neuropathy in vertebrates because they inhibit another esterase located in the nervous system, which has been termed neuropathy target esterase (NTE). This enzyme is described in Chapter 10, Section 10.2.4. OPs that cause delayed neuropathy include diisopropyl phosphofluoridate (DFP), mipafox, leptophos, methamidophos, and triorthocresol phosphate. The delay in the appearance of neurotoxic symptoms following exposure is associated with the aging process. In most cases, nerve degeneration is not seen with initial inhibition of the esterase but appears some 2-3 weeks after commencement of exposure, as the inhibited enzyme undergoes aging (see Section 16.4.1). The condition is described as OP-induced delayed neuropathy (OPIDN). 

Neuropathy target esterase (NTE) An esterase of the nervous system whose inhibition by certain OPs (e.g., mipafox, leptophos) can lead to the development of delayed neuropathy. 

Johnson, M.K. (1992). Molecular events in delayed neuropathy Experimental aspects of neuropathy target esterase. In B. Ballantyne and T.C. Marrs, (1992). Clinical and Experimental Toxicology of Organophosphates and Carbamates 90-113. 

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... 

FMC. 1991a. The effects of Durad 125 on serum cholinesterase and brain neuropathy. Target esterase activity in male Long-Evans rats. Study No 64460. FMC Corporation, Princeton, NJ. 

Maroni M, Bleecker ML. 1986. Neuropathy target esterase in human lymphocytes and platelets. JAppl Toxicol 6 1-7. 

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). 

Table 2 Reference Values of Lymphocyte and Platelet Neuropathy Target Esterase Activity...

Bertoncin, D., Russolo, A., Caroldi, S., and Lotti, M. (1985) Neuropathy target esterase in human lymphocytes, Archives on Environmental Health, 40 139-143. 

M. K. Johnson, P. Glynn, Active-Site Labelling and Purification of Neuropathy Target Esterase (NTE) Using a Biotinylated Organophosphorous Compound , Toxicologist 1993, 73,211. 

The test substance is administered orally in a single dose to domestic hens, which have been protected from acute cholinergic effects, when appropriate. The animals are observed for 21 days for behavioral abnormahties, ataxia, and paralysis. Biochemical measurements, in particular NTE (Neuropathy Target Esterase), are undertaken on hens randomly selected from each group (normally 24 and 48 h after dosing). Twenty-one days after exposure, the remainder of the hens is sacrificed and histopathological examination of selected neural tissues is undertaken. 

Exposure to some organophosphate cholinesterase inhibitors results in a delayed neuropathy characterized by degeneration of axons and myelin. This effect is not associated with the inhibition of acetylcholinesterase, but rather with the inhibition of an enzyme described as neuropathy target esterase (NTE) however, the exact mechanism of toxicity is not yet fully understood (Munro et al., 1994). For some organophosphate compounds, delayed neuropathy can be induced in experimental animals at relatively low exposure levels, whereas for others the effect is only seen following exposure to supralethal doses when the animal is protected from the acute toxic effects caused by cholinesterase inhibition. 

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