Blood enzymes cholinesterase inhibitions

Hydraulic fluids themselves cannot be measured in blood, urine, or feces, but certain chemicals in them can be measured. Aliphatic hydrocarbons, which are major components of mineral oil hydraulic fluids and polyalphaolefin hydraulic fluids, can be detected in the feces. Certain components of organophosphate ester hydraulic fluids leave the body in urine. Some of these fluids inhibit the enzyme cholinesterase. Cholinesterase activity in blood can be measured. Because many other chemicals also inhibit cholinesterase activity in blood, this test is not specific for organophosphate ester hydraulic fluids. This test is not available at most doctor s offices, but can be arranged at any hospital laboratory. See Chapters 2 and 6 for more information. 

Presently available methods to diagnose and biomonitor exposure to anticholinesterases, e.g., nerve agents, rely mostly on measurement of residual enzyme activity of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in blood. More specific methods involve analysis of the intact poison or its degradation products in blood and/or urine. These approaches have serious drawbacks. Measurement of cholinesterase inhibition in blood does not identify the anticholinesterase and does not provide reliable evidence for exposure at inhibition levels less than 20 %. The intact poison and its degradation products can only be measured shortly after exposure. Moreover, the degradation products of pesticides may enter the body as such upon ingestion of food products containing these products. 

Physostigmine is an interesting alkaloid because it is generally recognized that it acts by inhibiting a specific enzyme, cholinesterase. This enzyme has been found to be at characteristic levels in the corpuscles and blood plasma of different individuals (p. 79), and it would be expected that the action of the alkaloid in different individ-... 

The major action resulting from human exposure to diazinon is the inhibition of cholinesterase activity (refer to Section 2.4 for discussion). Two pools of cholinesterases are present in human blood acetylcholinesterase in erythrocytes and serum cholinesterase (sometimes referred to as pseudocholinesterase or butyrlcholinesterase) in plasma. Acetylcholinesterase, present in human erythrocytes, is identical to the enzyme present in neural tissue (the target of diazinon action) while serum cholinesterase has no known physiological function. Inhibition of both forms of cholinesterase have been associated with exposure to diazinon in humans and animals (Coye et al. 1987 Edson and Noakes 1960 Soliman et al. 1982). Inhibition of erythrocyte, serum, or whole blood cholinesterase may be used as a marker of exposure to diazinon. However, cholinesterase inhibition is a common action of anticholinesterase compounds such as organophosphates (which include diazinon) and carbamates. In addition, a wide variation in normal cholinesterase values exists in the general population, and there are no studies which report a quantitative... 

The toxicity of dichlorvos is due to inhibition of acetylcholinesterase and the signs of toxicity are generally similar to those caused by other organo-phosphorus insecticides. Dichlorvos is a direct inhibitor of cholinesterases thus, toxicity rapidly follows exposure and recovery is also rapid. With inhalation exposures, airway acetylcholinesterase inhibition is possible in the absence of significant blood enzyme inhibition. The fly head acetylcholinesterase appears more sensitive to inhibition by dichlorvos relative to mammalian brain acetylcholinesterase. At high doses, dichlorvos may cause hyperglycemia and abnormal glucose tolerance. 

To develop a PD model for cholinesterase-inhibiting compounds, the steady-state levels (p,mol) of B-esterase enzymes (AChE, BuChE. and CarbE) were determined for the variou.s tissues (c.g., brain, blood, liver, and diaphragm) based on the rates of enzyme synthesis (zero-order) and degradation (first-order) (Gearhart et al., 1990). The... 

The methods for determination of blood cholinesterases inhibition (AChE and BuChE) do not allow identification of the OP and do not provide reliable evidence for exposure at inhibition levels less than 20%. Moreover, they are less suitable for retrospective detection of exposure due to de novo synthesis of enzymes. A method has been developed which is based on reactivation of phosphylated cholinesterase and carboxylesterase (CaE) by fluoride ions. Treatment of the inhibited enzyme with fluoride ions can inverse the inhibition reaction, yielding a restored enzyme and a phos-phofluoridate which is subsequently isolated and quantified by gas chromatography and phosphorus-specific or mass spectrometric detection (Dll, Pll). Human (and monkey) plasma does not contain CaE but its BuChE concentration is relatively high [70-80 nM (M25, D8)], much higher than the concentration of AChE in blood [ca. 3 nM (H5)]. The plasma of laboratory animals, such as rats and guinea pigs, contains considerable concentrations... 

Historically, attempts to demonstrate cumulative affects among harvesters or other field workers have been frought with difficulty. For Instance an analysis of data generated by a 1970 EPA survey of 822 individuals in one California county found that farm workers had lower blood cholinesterase than similar non-field Individuals, that low blood enzyme levels were associated with symptoms of headache and enteric disturbances, and that at least some individuals exhibited seasonal inhibition but no clear seasonal trend was found for the group (24). In retrospect, this latter finding is not unexpected given not only the variability in pesticide use patterns both between and within crops, but even the variability within residues of a single pesticide-crop combination (, ). 

Organophosphates, such as methyl parathion, are known to inhibit cholinesterase activity. A method has been developed to measure the extent of this inhibition and relate it to organophosphate exposure (EPA 1980d Nabb and Whitfield 1967). In this EPA-recommended method, blood is separated into plasma and red blood cell fractions. The fractions are treated with saline solution, brought to pH 8 with sodium hydroxide, and dosed with acetylcholine perchlorate. The ensuing acetic acid releasing enzyme reaction... 

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. 

The above workers summarized the activity of D.F.P. by saying that the symptoms caused by it are explicable in terms of the inhibition of the cholinesterase enzymes of the tissues themselves and are not related immediately to the cholinesterase activity of the plasma or red blood cells. 

Disulfoton and its breakdown products can be measured in the blood, urine, feces, liver, kidney, or body fat of exposed people. In cases of occupational or accidental exposure to disulfoton, the breakdown products are often measured in the urine. The breakdown products are relatively specific for disulfoton and a few other similar organophosphate pesticides and can be detected in urine for up to one week after people were last exposed. Because disulfoton inhibits cholinesterase in blood and in blood cells, inhibition of this enzyme activity may also suggest exposure to disulfoton. Cholinesterase activity in blood and in blood cells may remain inhibited for as long as 1-2 weeks after the last exposure. Because other organophosphate pesticides also inhibit cholinesterase activity in blood and blood cells, this test is not specific for disulfoton. The measurement of cholinesterase in blood and blood cells and the amount of disulfoton breakdown products in the urine cannot always predict how much disulfoton you were exposed to. Your doctor can send samples of your blood or urine to special laboratories that perform these tests. Chapters 2 and 6 provide more information about medical tests. 

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