Acetylcholinesterase decreased

Exposure of two species of freshwater fish to 0.106 ppb of a commercial formulation containing 50% methyl parathion increased serum levels of T3 and reduced T4 (Bhattacharya 1993). This effect was attributed to inhibition of acetylcholinesterase activity in the fish brain, but no direct evidence was presented. Similar treatment of freshwater perch for 35 days resulted in decreased release of progesterone from the ovaries (Bhattacharya and Mondal 1997). Also, treatment of freshwater perch for up to 90 days with methyl parathion induced a decrease in the gonadosomatic index (not defined) after day 15 of... 

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. 

Compounds that affect activities of hepatic microsomal enzymes can antagonize the effects of methyl parathion, presumably by decreasing metabolism of methyl parathion to methyl paraoxon or enhancing degradation to relatively nontoxic metabolites. For example, pretreatment with phenobarbital protected rats from methyl parathion s cholinergic effects (Murphy 1980) and reduced inhibition of acetylcholinesterase activity in the rat brain (Tvede et al. 1989). Phenobarbital pretreatment prevented lethality from methyl parathion in mice compared to saline-pretreated controls (Sultatos 1987). Pretreatment of rats with two other pesticides, chlordecone or mirex, also reduced inhibition of brain acetylcholinesterase activity in rats dosed with methyl parathion (2.5 mg/kg intraperitoneally), while pretreatment with the herbicide linuron decreased acetylcholine brain levels below those found with methyl parathion treatment alone (Tvede et al. 1989). 

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. 

Acetylcholinesterase Plasma Cotumix quail Yes Decreased Dieter and... 

The dual inhibition of acetylcholinesterase and butyrylcholinesterase may lead to broader efficacy. As acetylcholinesterase activity decreases with disease progression, the acetylcholinesterase-selective agents may lose their effect, while the dual inhibitors may still be effective due to the added inhibition of butyrylcholinesterase. However, this has not been demonstrated clinically. 

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... 

Although this study (Hart 1980) did not identify an effect level, the NOAEL is below the LOEL found in all studies examining the toxicity of diisopropyl methylphosphonate. The LOEL for diisopropyl methylphosphonate is 262 mg/kg/day for male mink and 330 mg/kg/day for female mink (Bucci et al. 1997), doses at which statistically significant decreases in plasma cholinesterase (butyrylcholinesterase) but not RBC cholinesterase (acetylcholinesterase) activity were observed (Bucci et al. 1997). In general, a decrease in plasma cholinesterase activity is considered to be a marker of exposure rather than a marker of adverse effect, while a decrease in RBC acetylcholinesterase activity is a neurological effect thought to parallel the inhibition of brain acetylcholinesterase activity and is thus considered an adverse effect. Diisopropyl methylphosphonate was not found to inhibit red blood cell cholinesterase at doses at which plasma cholinesterase was significantly inhibited. No effects were observed in males at 45 mg/kg/day (Bucci et al. 1997) or at 63 mg/kg/day (Bucci et al. 1994), and no effects were observed in females at 82 mg/kg/day (Bucci et al. 1994), or at 57 mg/kg/day (Bucci et al. 1997). 

AChE = acetylcholinesterase Bd Wt = body weight BTP = butylated triphenyl phospate BUN = blood urea nitrogen (C) = capsule Cardio = cardiovascular d = day(s) deer. = decreased DBPP = dibutylated phenyl phosphate 2EDP = 2-ethylhexyl diphenyl phosphate Endocr = endocrine F = female (G) = gavage Gastro = gastrointestinal ... 

Enzymes can be used not only for the determination of substrates but also for the analysis of enzyme inhibitors. In this type of sensors the response of the detectable species will decrease in the presence of the analyte. The inhibitor may affect the vmax or KM values. Competitive inhibitors, which bind to the same active site than the substrate, will increase the KM value, reflected by a change on the slope of the Lineweaver-Burke plot but will not change vmax. Non-competitive inhibitors, i.e. those that bind to another site of the protein, do not affect KM but produce a decrease in vmax. For instance, the acetylcholinesterase enzyme is inhibited by carbamate and organophosphate pesticides and has been widely used for the development of optical fiber sensors for these compounds based on different chemical transduction schemes (hydrolysis of a colored substrate, pH changes). 

Absorbance- and reflectance-based measurements are widespread, as there are many enzymatic reaction products or intermediates that are colored or if not, can react with the appropriate indicator. Sensors using acetylcholinesterase for carbamate pesticides detection are an example of indirect optical fiber biosensors. This enzyme catalyses the hydrolysis of acetylcholine with concomitant decrease in pH41 ... 

A decrease in brain acetylcholinesterase activity in rats (Gietzen and Wooley 1984). 

No deaths. Exposure-dependent decrease in tissue acetylcholinesterase activity and increase in acetylcholine content LC50 (48-96 h)... 

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). 

The intermediate MRL is based on a NOAEL of 0.02 mg/m3 for decreased acetylcholinesterase activity in rats exposed to disulfoton 6 hours/day, 5 days/week for 3 weeks in a study by Thyssen (1980). 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). In the Thyssen (1980) study, 2 separate 3-week experiments... 

Among the specific enzymes whose activity has been reported to be decreased after in vitro ozone exposure are papain, glyceraldehyde-3-phosphate dehydrogenase, lysozyme, ribonuclease, and acetylcholinesterase. The latter enzyme appears to be particulady susceptible to free-radical and oxidative states. A loss in acetylcholinesterase activity has been reported in the red cells of humans and mice that inhaled ozone. However, there are only minimal amounts of this enzyme in lupg tissue, and, although it has been suggested that acetylcholinesterase is important in bronchial tract ciliary activity, there is no direct evidence to support this conjecture. 

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