Cholinesterases protective effects

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). 

Sevelova, L., Bajgar, J., Saxena, A., Doctor, B.P. (2004). Protective effect of equine hutyrylcholinesterase in inhalation intoxication of rats with sarin determination of blood and brain cholinesterase activities. Inhal. Toxicol. 16 531-6. 

The blood cholinesterases may, to some degree, provide a protective effect by binding with some fraction of the anticholinesterase compound (Raveh et al. 1997 Somani et al. 1992). However, not all nerve agents bind equally well with all cholinesterases. In tests conducted on dogs, Holmstedt (1951) found that GA affected RBC- and plasma-ChE to a nearly equal degree. In contrast, VX preferentially inhibits RBC-AChE, 70% compared with about 20% inhibition of plasma-ChE (Sidell and Groff 1974). 

Sevelova, L., Bajgar, J., Saxena, A., et al., 2004. Protective effect of equine butyrylcholinesterase in inhalation intoxication of rats with sarin determination of blood and brain cholinesterase activities. Inhal. Toxicol. 16,531—536. Stojiljkovic, M.R, Maksimovic, M., Bokonjic, D., et al., 1998. Adamantanes versus carbamates as prophylactic agents in soman-poisoned rats. In Proceedings from the 6th CBW Protection Symposium, Stockholm, May 10-15, 1998, pp. 197-202. 

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. 

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. 

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... 

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. 

Marquis, J.K. (ed.). 1988. Cholinesterase inhibition as an indication of adverse toxicologic effects. Review draft (June, 1988). Prepared for the Risk Assessment Forum, U.S. Environmental Protection Agency, Washington, DC. 

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