Red blood cell acetylcholinesterase

Consistent decreases in plasma cholinesterase may not have been observed in rats and dogs because they were treated with lower doses of diisopropyl methylphosphonate. In general, depression of plasma cholinesterase, also known as pseudocholinesterase or butyrylcholinesterase, is considered a marker of exposure rather than an adverse effect. Depression of cholinesterase activity in red blood cells (acetylcholinesterase) is a neurological effect thought to parallel the inhibition of brain acetylcholinesterase activity. It is considered an adverse effect. Acetylcholinesterase is found mainly in nervous tissue and erythrocytes. Diisopropyl methylphosphonate was not found to inhibit RBC... 

The inhibition of two cholinesterase activities in blood can also be used to confirm exposure to certain organophosphate ester compounds. Red blood cell acetylcholinesterase is the same cholinesterase found in the gray matter of the central nervous system and motor endplates of sympathetic ganglia. Synonyms for this enzyme include specific cholinesterase, true cholinesterase, and E-type cholinesterase. Plasma cholinesterase is a distinct enzyme found in intestinal mucosa, liver, plasma, and white matter of the central nervous system. Synonyms for this enzyme include nonspecific cholinesterase, pseudocholinesterase, butyrylcholinesterase, and S-type cholinesterase (Evans 1986). Nonspecific cholinesterase is thought to be a very poor indicator of neurotoxic effects. 

Storm JE, Rozman KK, Doull J Occupational exposure limits for 30 organophosphate pesticides based on inhibition of red blood cell acetylcholinesterase. Toxicology 2000 150 1. [PMID 10996660]... 

FIGURE 51.3. Plot of red blood cell acetylcholinesterase activity as a function of regenerated RBC sarin. 

Lorke, D.E., Hasan, M.Y., Arafat, K., Kuca, K., Musilek, K., Schmitt, A., Petroianu, G.A. (2008a). In vitro oxime reactivation of red blood cell acetylcholinesterase inhibitied by diisopropyl-fluorophosphate (DFP). J. Appl. Toxicol. 28 422-9. 

Zifrosilone (18) is a novel tight-binding inhibitor of acetylcholinesterase, which is in development as a potential therapeutic compound in the symptomatic treatment of Alzheimer s disease [72]. Pharmacokinetics and pharmacodynamics of the compound were studied in the dogs and rats after single intravenous and subcutaneous administrations. When evaluated in human healthy volunteers, the orally administered drug was well tolerated but displayed a strong dose-related inhibition of red blood cell acetylcholinesterase [73] and its development was consequently halted. 

Many individuals have genetic susceptibility to certain chemicals (Calabrese 1978). The influence of these genetic differences likely produces sub- and supersensitivity to OP insecticides and warfare agents (Russell and Overstreet 1987). Several enzymes with variations or polymorphisms control sensitivity to OPs red blood cell acetylcholinesterase, serum cholinesterase or pseudocholinesterase, lymphocyte neuropathy target esterase or platelet neuropathy target esterase (NTE), serum paroxonase, butyrylcholinesterase, and serum arylesterase (Costa et al. 1999 LaDu 1988 Li et al. 1993 Mutch et al. 1992). Inhibition of red blood cell acetylcholinesterase, in both the central and the peripheral nervous systems, produces acute symptoms (Mutch et al. 1992). Paroxonase and arylesterase further modify the response (LaDu 1988 Li et al. 1993). Variant, inactive butyrylcho-linesterases increase sensitivity to OPs (Lockridge and Masson 2000 Schwarz et al. 1995). OP-induced delayed polyneuropathy results... 

Organophosphorus compounds. Laboratory evidence of poisoning may be obtained by measuring decreases in the plasma pseudocholinesterase (PChE) and red blood cell acetylcholinesterase (AChE) activities. However, because of wide interindividual variability, significant depression of enzyme activity may occur but still fall within the normal range. It is most... 

Applicators and residents of dichlorvos (DDVP) treated structures were monitored for evidence of insecticide exposure using exposure pads, air samplers, serum and red blood cell acetylcholinesterase (AChE) tests, and urine analysis. There was no evidence of DDVP or dichloroacetic acid (DCAA) in the urine of applicators or cooperators. There were slight but significant differences (Pi0.05) in serum AChE activity of residents of treated units, but erythrocyte AChE was unchanged. Applicator AChE test results were inconclusive. It was concluded that there was not a significant risk. In terms of acute toxicity, to either the pesticide applicators or the residents of treated structures. 

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