Cholinesterase protection

In vitro, addition of IV and DFP simultaneously to red-cell cholinesterase protected the enzyme against Inhibition by DFP to a greater extent than the reactivation that the same concentration of the oxime (10 3 m) was capable of effecting after exposure of the enzyme to the same concentrations of DFP (1-3 x 10 g/ml). 

There is a second type of cholinesterase called butyrylcholinesterase, pseudocholinesterase, or cholinesterase. This enzyme is present in some nonneural cells in the central and peripheral nervous systems as well as in plasma and serum, the liver, and other organs. Its physiologic function is not known, but is hypothesized to be the hydrolysis of esters ingested from plants (Lefkowitz et al. 1996). Plasma cholinesterases are also inhibited by organophosphate compounds through irreversible binding this binding can act as a detoxification mechanism as it affords some protection to acetylcholinesterase in the nervous system (Parkinson 1996 Taylor 1996). 

The purpose of this chapter is not to discuss the merits, or lack thereof, of using plasma cholinesterase inhibition as an adverse effect in quantitative risk assessments for chlorpyrifos or other organophosphate pesticides. A number of regulatory agencies consider the inhibition of plasma cholinesterase to be an indicator of exposure, not of toxicity. The U.S. Environmental Protection Agency, at this point, continues to use this effect as the basis for calculating the reference doses for chlorpyrifos, and it is thus used here for assessing risks. 

Lander, F. and Hinke, K. (1992) Indoor application of anti-cholinesterase agents and the influence of personal protection on uptake, Arch. Environ. Contam. Toxicol., 22 163-166. 

Support Function Protective Clothing for Hazardous Chemicals Operations - NFPA 1993. Quincy, MA. Technical Bulletin - Assay Techniques for Detection of Exposure To Sulfur Mustard, Cholinesterase Inhibitors, Terrorism Incident Annex to the Federal Response Plan. Washington, D.C. 1995. 

Protection in vitro of cholinesterases against organo-phosphorus compounds... 

Work has been carried out to discover compounds which would protect cholinesterases against inhibition by tabun, sarin and D.F.P.1 Sixteen amino acids were examined for this pur pose in connexion with sarin and only D.O.P.A. (3 4-dihydroxy... 

It was found that catechol derivatives in general were able to protect cholinesterases in vitro. Both horse-serum and rat-brain cholinesterases were protected against the above inhibitors. It is thought that the basis of the protection is a reaction between catechol and the inhibitor. 

It has been suggested by Augustinsson1 that adrenaline and noradrenaline can protect cholinesterase. However, adrenaline cannot protect below a concentration of 0-1 mM, and it is therefore unlikely that mobilization of adrenaline in vivo could influence the inhibition of cholinesterase. 

Immediately following the injection of pseudo-cholinesterase, rabbits were protected against the effect of benzoylcholine and were unaffected by a dose of it which would normally have paralysed them. 

The key to successful brain protection for Alzheimer s disease is the newly introduced NMDA receptor antagonist, memantine. Family members should be advised that the protection provided by memantine will slow the progression of Alzheimer s disease, but it does not halt or reverse the course of the illness. Memantine is now commonly coadministered with a cholinesterase inhibitor. 

Scalfe, J.F. Protection of human red cell cholinesterase against inhibition by tabun and 0,O-diethyl-S-2-diethyl-aminoethyl phosphorothiolate. Can. J. Biochem. Physiol. 38 301-303, 1960. 

The protective activity of IV against lethal Intoxication by OF compounds has been thought to be exerted principally by promoting reactivation of Inhibited cholinesterase. IV has been found to... 

Schaumann OO found that pretreatment of mice with 2-PAM 1 reduced inhibition of acetylcholinesterase in brain by paraoxon much more effectively than those by DFP and 217-A0. The finding of some protection against all three OP compounds could depend on direct reaction between the last two inhibitors and the oxime, with a reduction in inhibition of the enzyme. A similar consideration applies to the report by Bisa et al. that IV protected serum and brain cholinesterase from inhibition by paraoxon administered later at twice the LD5O. Although the same intraperitoneal dose of IV (7 mg) was found to protect the cholinesterase of rat serum and brain only incompletely from inhibition by DFP at 5 times the LD50, that of serum recovered its normal activity by 20 h after the dose of DFP, whereas that of brain required 26 h for recovery. 

PAM I seems to be less effective than IV In reactivating brain cholinesterase after its inactivation by paraoxon or other OP compounds.There was early evidence that 2-PAM I produced more reactivation of cholinesterase in the pontomedullary region and the area postrema that had been inhibited by paraoxon than in the cerebellum and the cerebral cortex TO and that it could prevent the appearance of grand mal-llke discharges in EEGs of rabbits after doses of sarin that evoked such discharges in rabbits not protected... 

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