Erythrocytes acetylcholinesterase

Acetylcholinesterase (EC 3.1.1.7) (AChE) Acetylcholine acetylhydrolase True ChE ChE I ChE Acet-ylthiocholinesterase Acetylcholine hydrolase Acetyl (3-methylcholinesterase Erythrocyte ChE Butyrylcholinesterase (EC 3.1.1.8) (BChE or BuChE) ChE Pseudocholinesterase Plasma ChE Acylcholine acylhydrolase Non-specific ChE ChEII Benzoylcholinesterase Propionylcholinesterase... 

Acetylcholinesterase contained in erythrocytes is identical to that found in the nervous system. Its function within erythrocytes may be to control permeability of the cell membrane, to an extent. 

Functional neurological changes due to acute organophosphate exposure generally correlate with acetylcholinesterase inhibition in erythrocytes (Wills 1972). 

The only other information regarding the potential for age-related differences in susceptibility to methyl parathion came from a study by Garcia-Lopez and Monteoliva (1988). The investigators showed increasing mean erythrocyte acetylcholinesterase activity levels with increasing age range, starting at birth (in 10-year increments and >60 years of age) in both males and females. However, it is not known whether increased erythrocyte acetylcholinesterase activity indicates a decreased susceptibility to methyl parathion toxicity. 

Following exposure of humans to organophosphates, but not specifically methyl parathion, restoration of plasma cholinesterase occurs more rapidly than does restoration of erythrocyte cholinesterase (Grob et al. 1950 Midtling et al. 1985). These findings are supported by studies of methyl parathion in animals. Erythrocyte cholinesterase levels are representative of acetylcholinesterase levels in the nervous system, and, therefore, may be a more accurate biomarker of the neurological effects of chronic low level exposure of humans to methyl parathion (Midtling et al. 1985 NIOSH 1976). 

Individuals with hereditary low plasma cholinesterase levels (Kalow 1956 Lehman and Ryan 1956) and those with paroxysmal nocturnal hemoglobinuria, which is related to abnormally low levels of erythrocyte acetylcholinesterase (Auditore and Hartmann 1959), would have increased susceptibility to the effects of anticholinesterase agents such as methyl parathion. Repeated measurements of plasma cholinesterase activity (in the absence of organophosphate exposure) can be used to identify individuals with genetically determined low plasma cholinesterase. 

Evans and Wroe 1980 Evans et al. 1988 Howard et al. 1978 Sanz et al. 1991 Venkataraman et al. 1990) and significantly increased erythrocyte acetylcholinesterase levels (De Peyster et al. 1994 Sanz et al. 1991 Venkataraman et al. 1990) during pregnancy. It is not known whether these differences might make pregnant women more susceptible to methyl parathion toxicity. 

Several studies in animals suggest that age may affect susceptibility to methyl parathion toxicity, and that children may be more susceptible than adults, but the data are limited. (See Section 3.7 for more information on Children s susceptibility.) A study in humans showed that mean erythrocyte acetylcholinesterase activity levels increase with increasing age from birth through old age in both sexes (Garcia-Lopez ad Monteoliva 1988), but it is not known whether increased erythrocyte acetylcholinesterase activity indicates decreased susceptibility to methyl parathion. 

Auditore JV, Hartmann RC. 1959. Paroxysmal nocturnal hemoglobinuria—II. Erythrocyte acetylcholinesterase defect. Am J Med 27 401-410. 

Diabetic patients have reduced antioxidant defences and suffer from an increased risk of free radical-mediated diseases such as coronary heart disease. EC has a pronounced insulin-like effect on erythrocyte membrane-bound acetylcholinesterase in type II diabetic patients (Rizvi and Zaid, 2001). Tea polyphenols were shown to possess anti-diabetic activity and to be effective both in the prevention and treatment of diabetes (Choi et al, 1998 Yang et al, 1999). The main mechanism by which tea polyphenols appear to lower serum glucose levels is via the inhibition of the activity of the starch digesting enzyme, amylase. Tea inhibits both salivary and intestinal amylase, so that starch is broken down more slowly and the rise in serum glucose is thus reduced. In addition, tea may affect the intestinal absorption of glucose. 

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... 

Organophosphate Ester Hydraulic Fluids. Interpretation of the biomarkers of exposure to organophosphate ester hydraulic fluids is complicated by the diversity of composition among the hydraulic fluids in this class. Erythrocyte acetylcholinesterase activity is a good biomarker of exposure to certain organophosphates (e.g., insecticides), but results are inconsistent with organophosphate components of... 

Perry NSL, Houghton P, Theobald A, Jenner P and Perry EK (2000). In-vitro inhibition of human erythrocyte acetylcholinesterase by Salvia lavandulaefolia essential oil and constituent terpenes. Journal of Pharmacy and Pharmacology, 52, 895-902. 

Seto, Y. and T. Shinohara. 1987. Inhibitory effects of paraquat and its related compounds on the acetylcholinesterase activities of human erythrocytes and electric eel (Electrophorus electricus). Agric. Biol. Chem. 51 2131-2138. 

Inhibition of the two principal human cholinesterases, acetylcholinesterase and pseudocholinesterase, may not always result in visible neurological effects (Sundlof et al. 1984). Acetylcholinesterase, also referred to as true cholinesterase, red blood cell cholinesterase, or erythrocyte cholinesterase is found in erythrocytes, lymphocytes, and at nerve synapses (Goldfrank et al. 1990). Inhibition of erythrocyte or lymphocyte acetylcholinesterase is theoretically a reflection of the degree of synaptic cholinesterase inhibition in nervous tissue, and therefore a more accurate indicator than pseudocholinesterase activity of inhibited nervous tissue acetylcholinesterase (Fitzgerald and Costa 1993 Sundlof et al. 1984). Pseudocholinesterase (also referred to as cholinesterase, butyrylcholinesterase, serum cholinesterase, or plasma cholinesterase) is found in the plasma, serum, pancreas, brain, and liver and is an indicator of exposure to a cholinesterase inhibitor. 

The MRL is based on a NOAEL of 0.5 mg/m3 for decreased acetylcholinesterase activity in rats exposed to disulfoton 4 hours/day for 5 days in a study by Thyssen (1978). The NOAEL was adjusted for intermittent exposure, converted to a human equivalent concentration, and divided by an uncertainty factor of 30 (3 for extrapolation from animals to humans and 10 for human variability). Inhibition of erythrocyte cholinesterase activity and unspecified behavioral disorders were observed at 1.8 mg/m, and unspecified signs of cholinergic toxicity were observed at 9.8 mg/m. Similar effects were observed in rats or mice exposed to higher concentrations for shorter duMtions (Doull 1957 Thyssen 1978). The NOAEL value of 0.5 mg/m is supported by another study, in which no significant decrease in the activity of brain, serum, or submaxillary gland cholinesterase was found in rats exposed to 0.14-0.7 mg/m for 1 hour/day for 5-10 days (DuBois and Kinoshita 1971). Mild depression of erythrocyte cholinesterase activity was reported in workers exposed by the inhalation and dermal routes (Wolfe et al. 1978). 

Inhibition of erythrocyte acetylcholinesterase activity or serum cholinesterase activity with or without concomitant neurological signs is usually a good indicator of organophosphate exposure. In addition, T-lymphocyte acetylcholinesterase activity was found to be rapidly and greatly depressed in rats during a 14-day daily exposure to disulfoton, but rapidly recovered after exposure (Fitzgerald... 

Because cholinesterase inhibition is a very sensitive biomarker for other chemicals, it is not always conclusive evidence of disulfoton exposure. However, depression of cholinesterase activity can alert a physician to the possibility of more serious neurological effects. Erythrocyte acetylcholinesterase activity more accurately reflects the degree of synaptic cholinesterase inhibition in nervous tissue, while serum cholinesterase activity may be associated with other sites (Goldfrank et al. 1990). In addition, a recent study showed that after rats received oral doses of disulfoton for 14 days, acetylcholinesterase levels in circulating lymphocytes correlated better with brain acetylcholinesterase activity than did erythrocyte cell cholinesterase activities during exposure (Fitzgerald and Costa 1993). However, recovery of the activity in lymphocytes was faster than the recovery of activity in the brain, which correlated better with the activity in erythrocytes. Animal studies have also demonstrated that brain acetylcholinesterase depression is a sensitive indicator of neurological effects (Carpy et al. 1975 Costa et al. 1984 Schwab and Murphy 1981 Schwab et al. 1981, 1983) however, the measurement of brain acetylcholinesterase in humans is too invasive to be practical. 

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