Serum Cholinesterase Activity Research Articles

Impact of Exposure to Fenitrothion on Vital Organs in Rats.

This study was designed to investigate the impact of oral administration of fenitrothion (10 mg/kg) on liver, kidney, brain, and lung function in rats. The effect was studied on days 7, 14, 21, 28, and 42. Our results have shown deterioration in liver function as evidenced by the elevation in serum ALT, AST, ALP, and bilirubin and reduction in albumin and hepatic glycogen. This was associated with a state of hyperglycemia and hyperlipidemia and increased prothrombin time, while hemoglobin content was reduced. In addition, the kidney function was reduced as indicated by the elevation in serum creatinine, uric acid, and BUN, while the serum levels of magnesium, potassium, and sodium were reduced. This study also showed an impairment in brain neurotransmitter (elevated 5-HT, glutamate, GABA, and reduced dopamine and norepinephrine level). This was associated with a reduction in the barrier capacity in brain and lung. Fenitrothion also caused a decrease in cholinesterase activity in serum, lung, and brain activity associated with a state of oxidative stress in all tested organs and hyperammonemia. These results support the hazards of pesticide use and shows the importance of minimizing pesticide use or discovering new safe pesticides.

The Effect of Cholinesterase Activity on the Diagnosis and Prognosis of Sepsis

Background: There are many biomarkers defined for systemic inflammation and sepsis. Cholinesterase and its biological role is not entirely known but in recent studies, it was seen that cholinesterase levels had a diagnostic value in predicting both sepsis and mortality. Objective: The purpose of this study is to establish the role of cholinesterase activity as a biomarker in the early diagnosis and treatment planning of sepsis which is an uncontrolled inflammatory response of the host to an infection. Materials and Method: This is a controlled, observational, and prospective clinical study and has been carried out on patients admitted to the intensive care unit with sepsis. The demographic features, the medical history and vital findings of the patients were recorded. According to the intensive care monitoring and treatment procedures, the complete blood count test, urine test and routine biochemical assessments particularly the CRP, procalcitonin and blood gasses tests were performed and the serum cholinesterase activity was assessed. The data was digitalized and then analyzed using the SPSS 15.0 software package. Results: The cholinesterase levels detected in the patient group were lower than the cholinesterase levels of the control group and there was a significant difference between the groups (p< 0.001). A statistically significant association was detected between the severity of sepsis and the cholinesterase levels of the patients. There was also a statistical relationship between the cholinesterase levels and being connected to mechanical ventilation and the use of vasopressors (p<0.05). There was a significant association between mortality and cholinesterase levels (p= 0.009). As the cholinesterase activity decreased the mortality rate increased. As a result of the ROC analyses performed to establish the diagnostic value of the patients' cholinesterase levels in predicting sepsis and morality it was seen that cholinesterase levels had a diagnostic value in predicting both sepsis and mortality. Conclusions: We believe that the cholinesterase activity investigated in our study is an extremely useful biomarker in the diagnosis and prognosis prediction of the sepsis syndrome that progresses with systemic inflammation.

The influence of sodium bicarbonate combined with ulinastatin on cholinesterase activity for patients with acute phoxim pesticide poisoning

To observe the effect of sodium bicarbonate combined with ulinastatin on cholinesterase activity for patients with acute phoxim pesticide poisoning. A total of 67 eligible patients with acute phoxim pesticide poisoning, Who were admitted to the emeryency department of hospital from March 2011 to February 2014, Acording to different treatments au patients were randomly divided into the conventional treatment group (n=34) and the sodium bicarbonate+ulinastatin group (n=35) . The conventional treatment group were given thorough gastric lavage with water, the sodium bicarbonate + ulinastatin group were given gastric lavage with 2% sodium bicarbonate solution. Both groups were given such treatments as catharsis, administration of oxygen, fluid infusion, diuresis, and antidotes such as atropine and pralidoxime methylchloride. On the basis of comprehensive treatment, people in the sodium bicarbonate+ulinastatin group were given 5% sodium bicarbonate injection and ulinastatin. The clinical effect of the two groups were compared. The serum cholinesterase activity of the sodium bicarbonate+ulinastatin group was significantly higher than the conventional treatment group from the 5th day, and the difference was statistically significant (P<0.05) . The total atropine dosage, total pralidoxime methylchloride dosage and hospitalization days were better than the conventional treatment group, and the differences were statistically significant (P<0.05) . The difference in the time of atropinization between the two groups was not statistically significant (P>0.05) . The results of arterial blood pH, HCO3- of the sodium bicarbonate + ulinastatin group were higher than the conventional treatment group, and the difference of HCO3- at the 10th day was statistically significant (P<0.05) . Sodium bicarbonate combined with ulinastatin can improve the therapeutic effect and reduce complications in the treatment of acute phoxim pesticide poisoning, and have beneficial effects on the recovery of cholinesterase activity.

Uso de marcadores genotoxicológicos para la evaluación de agricultores expuestos a plaguicidas organofosforados

Introducción: Los plaguicidas organofosforado son compuestos utilizados para el control de plagas en actividades agrícolas; genera exposición ocupacional asociada a posibles intoxicaciones agudas y crónicas que se manifiestan por alteraciones a nivel bioquímico, molecular y genético, los cuales pueden ser evaluados mediante el uso de marcadores genotoxicológicos. Objetivo: Determinar el uso de marcadores genotoxicológicos para la evaluación de agricultores expuestos a plaguicidas organofosforados. Diseño: Observacional, analítico, transversal con grupo control. Lugar: Empresa de agroexportación de espárragos en el Distrito de Virú, La Libertad. Intervenciones: Se determinó la actividad enzimática de la colinesterasa sérica (BChE) y eritrocitaria (AChE), y se hizo ensayos de genotoxicidad (aberraciones cromosómicas, ensayo cometa y micronúcleos) en 59 trabajadores expuestos a plaguicidas (grupo expuesto) y 50 personas sin exposición a plaguicidas (grupo control). Principales medidas de resultados: Actividad enzimática de la colinesterasa sérica (BChE) y eritrocitaria (AChE), y ensayos de genotoxicidad (aberraciones cromosómicas, ensayo cometa y micronúcleos). Resultados: Las edades promedio del grupo expuesto y control fueron de 39,6±10,8 y 34,0±11,5 años, respectivamente. En referencia a la actividad BChE, se encontró diferencia significativa (p&amp;lt;0,001) entre el grupo expuesto (4 733.0±1 350.1 U/L) y control (7 075.0±1 674.0 U/L). Caso contrario se presentó en la actividad AChE entre el grupo expuesto (4 867,0±632,2 U/L) y control (5 051,0±505,5 U/L). Además, se evidenció la inhibición de ambas enzimas en 9 trabajadores expuestos por debajo del valor de referencia. No se evidenció diferencias significativas en los marcadores genotoxicológicos, a excepción del recuento de micronúcleos, puentes nucleoplásmicos, gemaciones, binucleaciones celulares y cariorexis de células de epitelio bucal; y en la evaluación del daño al ADN mediante el ensayo cometa (p&amp;lt;0,05) se obtuvo promedios de intensidad de cola de 8,28±1,85 (Rango: 6,06-15,75) y 7,30±1,25 (Rango: 4,04-9,41) para el grupo expuesto y control, respectivamente. Conclusiones: El uso de marcadores genotoxicológicos aporta información relevante como herramienta que permite predecir el riesgo asociado a cáncer, considerando que el evento inicial es el daño al ácido desoxiribonucléico (ADN) en cualquier etapa del ciclo celular; además, existió asociación significativa entre el efecto genotóxico y la exposición a plaguicidas organofosforados evidenciada por la inhibición de la BChE.

Serum Total Cholinesterase Activity on Admission Is Associated with Disease Severity and Outcome in Patients with Traumatic Brain Injury.

BackgroundTraumatic brain injury (TBI) is one of the leading causes of neurological disability. In this retrospective study, serum total cholinesterase (ChE) activities were analyzed in 188 patients for diagnostic as well as predictive values for mortality.Methods and FindingsWithin 72 hours after injury, serum ChE activities including both acetylcholinesterase and butyrylcholinesterase were measured. Disease severity was evaluated with Acute Physiology and Chronic Health Evaluation (APACHE) II score, Glasgow Coma Score, length of coma, post-traumatic amnesia and injury feature. Neurocognitive and functional scores were assessed using clinical records. Of 188 patients, 146 (77.7%) survived and 42 (22.3%) died within 90 days. Lower ChE activities were noted in the non-survivors vs. survivors (5.94±2.19 vs. 7.04±2.16 kU/L, p=0.023), in septic vs. non-infected patients (5.93±1.89 vs. 7.31±2.45 kU/L, p=0.0005) and in patients with extremely severe injury vs. mild injury (6.3±1.98 vs. 7.57±2.48 kU/L, p=0.049). The trajectories of serum ChE levels were also different between non-survivors and survivors, septic and non-infected patients, mild and severely injured patients, respectively. Admission ChE activities were closely correlated with blood cell counts, neurocognitive and functional scores both on admission and at discharge. Receiver operating characteristic analysis showed that the area under the curve for ChE was inferior to that for either APACHE II or white blood cell (WBC) count. However, at the optimal cutoff value of 5 kU/L, the sensitivity of ChE for correct prediction of 90-day mortality was 65.5% and the specificity was 86.4%. Kaplan-Meier analysis showed that lower ChE activity (<5 kU/L) was more closely correlated with poor survival than higher ChE activity (>5 kU/L) (p=0.04). After adjusting for other variables, ChE was identified as a borderline independent predictor for mortality as analyzed by Binary logistic regression (P=0.078).ConclusionsLowered ChE activity measured on admission appears to be associated with disease severity and outcome for TBI patients.

Serum cholinesterase activity as an early indicator of systemic inflammation

Early diagnosis of systemic inflammation, a generalised response to noxious stimuli, is fundamentally important for effective and goal-directed therapy. Various inflammation biomarkers have been used in clinical and experimental practice. However, a definitive diagnostic tool for an early detection of systemic inflammation remains to be identified. Acetylcholine (Ach) has been shown to play an important role in the inflammatory response. Serum cholinesterase (butyrylcholinesterase (BChE)) is the major Ach hydrolyzing enzyme in plasma. The role of this enzyme during inflammation has not yet been fully understood. Here, we describe a correlation between the BChE activity and the early systemic inflammatory response upon traumatic injury.

Dynamic changes of serum cholinesterase activity after severe trauma.

The aim of the present study was to examine dynamic changes in serum cholinesterase (ChE) activity during early-stage severe trauma and the clinical significance of these changes. This prospective, observational study included 81 patients with severe trauma who were treated between October 2011 and April 2013 in the emergency intensive care unit (EICU) of a university-affiliated, tertiary-care, grade A general hospital in China. Serum ChE activity was measured on Days 1, 3, and 7 post-injury. The correlation of dynamic changes in serum ChE activity with trauma severity and prognosis was assessed. Correlations between changes in serum ChE activity after injury and albumin (ALB), prealbumin (PAB), transferrin (TRF), and C-reactive protein (CRP) levels were also analyzed. Serum ChE activity in trauma patients was 42.3%-50.2% lower on Days 1, 3, and 7 compared with the control (P<0.001 for all time points), and it continued to decrease after Day 7 in both the survival and death subgroups. In the subgroup with an injury severity score (ISS) of ≤25, serum ChE activity initially decreased, but eventually increased. However, activity decreased continuously in the ISS>25 subgroup. ChE activity was significantly lower in both the death and the ISS>25 subgroups than in the survival and ISS≤25 subgroups on Days 1, 3, and 7 after injury. Activity was negatively correlated with ISS and acute physiology and chronic health evaluation III (APACHE III) at all time points. When comparing the receiver operating characteristic (ROC) curves for predicting prognosis, the area under the curve (AUC) in the plot of serum ChE was similar to the AUCs in plots of ISS and APACHE III, but significantly smaller than the AUC in the plot of the trauma and injury severity score (TRISS). Serum ChE activity was positively correlated with ALB, PAB, and TRF at all time points post-injury. Activity was not significantly correlated with CRP on Day 1, but was significantly and negatively correlated with CRP on Days 3 and 7. There is a significant decrease in serum ChE activity after severe trauma. Serum ChE may be regarded as a negative acute phase protein (APP) and the dynamic changes in serum ChE may be useful as an auxiliary indicator for evaluating trauma severity and predicting prognosis.

Pharmacokinetics and effects on serum cholinesterase activities of organophosphorus pesticides acephate and chlorpyrifos in chimeric mice transplanted with human hepatocytes

Organophosphorus pesticides acephate and chlorpyrifos in foods have potential to impact human health. The aim of the current study was to investigate the pharmacokinetics of acephate and chlorpyrifos orally administered at lowest-observed-adverse-effect-level doses in chimeric mice transplanted with human hepatocytes. Absorbed acephate and its metabolite methamidophos were detected in serum from wild type mice and chimeric mice orally administered 150mg/kg. Approximately 70% inhibition of cholinesterase was evident in plasma of chimeric mice with humanized liver (which have higher serum cholinesterase activities than wild type mice) 1day after oral administrations of acephate. Adjusted animal biomonitoring equivalents from chimeric mice studies were scaled to human biomonitoring equivalents using known species allometric scaling factors and in vitro metabolic clearance data with a simple physiologically based pharmacokinetic (PBPK) model. Estimated plasma concentrations of acephate and chlorpyrifos in humans were consistent with reported concentrations. Acephate cleared similarly in humans and chimeric mice but accidental/incidental overdose levels of chlorpyrifos cleared (dependent on liver metabolism) more slowly from plasma in humans than it did in mice. The data presented here illustrate how chimeric mice transplanted with human hepatocytes in combination with a simple PBPK model can assist evaluations of toxicological potential of organophosphorus pesticides.

A Study on Beta-Glucuronidase Enzyme as a Probable Biomarker in Cases of Acute Poisoning by Cholinesterase Enzyme Inhibitor Insecticides

Acute poisoning by cholinesterase enzyme inhibitors insecticide continues to be a detrimental problem and a potential cause of mortality especially in developing countries. Early intervention in such cases is proven to be helpful. The aim of the present work was to assess the role of serum β-glucuronidase level as probable marker for the assessment of acute cholinesterase enzyme inhibitors insecticides poisoning. Subjects and methods: the study included 60 cases of acute poisoning by cholinesterase enzyme inhibitors insecticides, admitted to the Poison unit of Alexandria Main University Hospital, another 15 healthy volunteers were included as control group. All the cases were subjected to: thorough history taking, full clinical examination, grading of poisoning severity score (PSS), laboratory investigations (serum cholinesterase activity level (CHE) and serum β-glucuronidase level (βG). Results: Serum CHE levels were significantly decreased, while Serum βG were significantly increased in the patients compared with the controls, and also, with increasing severity of poisoning. A significant negative correlation was detected between level of serum CHE and duration of hospitalization, while a significant positive correlation was found between serum level of βG and length of hospital stay. In addition, a significant inverse correlation was found between levels of CHE and βG whether in control group or in cases. Data obtained from ROC curve analysis revealed that serum βGlevel was more helpful in diagnosis of OP poisoning than CHE (accuracy 100% versus 80%), while both serum CHE andβG levels were of equal accuracy percentage for detection of poisoning severity and for prediction of outcome (100% and 91.67% each). Conclusion: SerumβG could be used as a good biomarker for the diagnosis and prognosis of cholinesterase enzyme inhibitors insecticide poisoning.

C5 variant is associated with decreased risk of coronary artery disease in outpatients with severe hypercholinesterasemia.

Although the C5 variant of cholinesterase is known to be a cause of hypercholinesterasemia, the pathophysiological significance of the C5 variant and the C5 variant-related hypercholinesterasemia in cardiovascular diseases remain unclear. The present study aimed to clarify the pathophysiological significance of the C5 variant as a risk or protective factor for coronary artery disease (CAD) in patients with severe hypercholinesterasemia. Severe hypercholinesterasemia was defined as serum cholinesterase (ChE) activity >= 450 IU/L (>= 2.0 SD). We screened 11,648 consecutive outpatients between 2005 and 2011 at Toho University, Sakura Medical Center. In patients with severe hypercholinesterasemia, phenotyping of the C5 variant was conducted using polyacrylamide gel electrophoresis and alpha-naphthyl butyrate staining. 157 subjects (1.4% of 11,648 outpatients screened) were diagnosed with severe hypercholinesterasemia (mean serum ChE activity 574 ± 109 IU/L), and the frequency of the C5 variant was 45.2%. Subjects with the C5 variant had higher age, lower body mass index, milder dyslipidemia and liver dysfunction, and lower rates of hypertension and CAD compared with subjects without the C5 variant. Multivariate logistic regression model demonstrated that the presence of C5 variant independently lowered the risk of CAD, with odds ratio 0.071 (95% confidence interval (CI) 0.007 - 0.763, p = 0.029). The prevalence of the C5 variant was relatively high, and the C5 variant is associated with decreased risk of CAD in outpatients with severe hypercholinesterasemia.

Chemical composition, antimicrobial, antioxidative and anticholinesterase activity of Satureja Montana L. ssp montana essential oil

Abstract The present study investigates the chemical compositions of three Satureja montana L. ssp montana essential oils and correlates chemical variability with biological activities. GC/MS analysis showed that with an increase in altitude (100–500–800 m), a higher content of linalool, terpinen-4-ol and cis-sabinene hydrate was found, while the percentage of phenolic compounds, thymol and carvacrol decreased. Antimicrobial activity of the essential oils was tested against 7 fungal and 23 bacterial strains. The essential oil characterized by the highest content of phenols and alcohols exhibited the highest antimicrobial potential. The correlation analysis showed that the major carriers of the obtained antioxidant activity are oxygenated monoterpenes. All essential oils inhibited human serum cholinesterase activity. High antimicrobial potential, together with moderate antioxidant capacity and strong inhibition of human serum cholinesterase, classifies S. montana essential oil as a natural source of compounds that can be used in the treatment of foodborne and neurological diseases, wound and other infections, as well as for general health improvement.

Body mass index as a prognostic factor in organophosphate-poisoned patients

Organophosphate poisoning is a serious clinical entity and considerable morbidity and mortality. Several factors have been identified to predict outcomes of organophosphate poisoning. Organophosphates are lipophilic and therefore predicted to have a large volume of distribution and to rapidly distribute into tissue and fat. Thus, toxic effects of organophosphate would be expected to last longer in obese patients. We investigated the relationship between obesity and clinical course in 112 acute organophosphate-poisoned patients from an initial medical record review of 234 patients. One hundred twenty-two patients were excluded: 6 were children, 14 had an uncertain history of exposure and of uncertain agent, 10 were transferred to another hospital, 67 were discharged from the emergency department because their toxicity was mild, 21 had carbamate poisoning, and 4 did not have height or weight checked. Clinical features, body mass index, Glasgow Coma Scale, laboratory findings, serum cholinesterase activity, electrocardiogram finding, management, and outcomes were examined. The lipid solubility of the implicated organophosphate was characterized by its octanol/water coefficient. Forty of 112 patients were obese. Obese patients who were poisoned by high lipophilicity organophosphate compounds had a need for longer use of mechanical ventilation, intensive care unit care, and total length of admission. Body mass index can provide a guide to physicians in predicting clinical course and management in organophosphate-poisoned patients.

Pesticide-contaminated feeds in integrated grass carp aquaculture: toxicology and bioaccumulation

Effects of dissolved pesticides on fish are widely described, but little is known about effects of pesticide-contaminated feeds taken up orally by fish. In integrated farms, pesticides used on crops may affect grass carp that feed on plants from these fields. In northern Vietnam, grass carp suffer seasonal mass mortalities which may be caused by pesticide-contaminated plants. To test effects of pesticide-contaminated feeds on health and bioaccumulation in grass carp, a net-cage trial was conducted with 5 differently contaminated grasses. Grass was spiked with 2 levels of trichlorfon/fenitrothion and fenobucarb. Unspiked grass was used as a control. Fish were fed at a daily rate of 20% of body mass for 10 d. The concentrations of fenitrothion and fenobucarb in pond water increased over time. Effects on fish mortality were not found. Fenobucarb in feed showed the strongest effects on fish by lowering feed uptake, deforming the liver, increasing blood glucose and reducing cholinesterase activity in blood serum, depending on feed uptake. Fenobucarb showed increased levels in flesh in all treatments, suggesting bio-concentration. Trichlorfon and fenitrothion did not significantly affect feed uptake but showed concentration-dependent reduction of cholinesterase activity and liver changes. Fenitrothion showed bioaccumulation in flesh which was dependant on feed uptake, whereas trichlorfon was only detected in very low concentrations in all treatments. Pesticide levels were all detected below the maximum residue levels in food. The pesticide-contaminated feeds tested did not cause mortality in grass carp but were associated with negative physiological responses and may increase susceptibility to diseases.

Sublethal Dose of Diazinon Induces Pulmonary Toxicity in Rat: Histopathological Evidence

Objective: Diazinon (DZ) is a widely used contact organophosphorous pesticide with broad spectrum insecticide activity. The extensive use of DZ has caused great concern due to the hazardous side effects on human beings as well as wild and domestic animals. The aim of this study was to investigate the effect of sublethal dose of DZ on rat lung. Material and methods: Seven groups of male Wistar rats were used comprising control and test groups. The control group received corn oil (0.3 ml/day) for 60 days by oral gavages. The test groups received DZ at a dose of 60 mg/kg body weight orally for 2, 10, 24, 30, 54 and 60 days, respectively. Results: The histopathological analysis of the lungs in DZ-treated groups revealed congestion on day 2, pulmonary edema and emphysema on day 10, congestion and atelectasia on day 24, infiltration of mononuclear cells on day 30 and pulmonary hemorrhage along with bronchial glands hyperplasia on days 54 and 60. DZ administration also caused a significant decrease in serum cholinesterase activity in a time-dependent manner. Conclusion: These findings indicate that sublethal dose of DZ can induce severe lesions in the lung of rat.

Acetylcholinesterase (AChE) inhibition aggravates fasting-induced triglyceride accumulation in the mouse liver

Although fasting induces hepatic triglyceride (TG) accumulation in both rodents and humans, little is known about the underlying mechanism. Because parasympathetic nervous system activity tends to attenuate the secretion of very-low-density-lipoprotein-triglyceride (VLDL-TG) and increase TG stores in the liver, and serum cholinesterase activity is elevated in fatty liver disease, the inhibition of the parasympathetic neurotransmitter acetylcholinesterase (AChE) may have some influence on hepatic lipid metabolism. To assess the influence of AChE inhibition on lipid metabolism, the effect of physostigmine, an AChE inhibitor, on fasting-induced increase in liver TG was investigated in mice. In comparison with ad libitum-fed mice, 30h fasting increased liver TG accumulation accompanied by a downregulation of sterol regulatory element-binding protein 1 (SREBP-1) and liver-fatty acid binding-protein (L-FABP). Physostigmine promoted the 30h fasting-induced increase in liver TG levels in a dose-dependent manner, accompanied by a significant fall in plasma insulin levels, without a fall in plasma TG. Furthermore, physostigmine significantly attenuated the fasting-induced decrease of both mRNA and protein levels of SREBP-1 and L-FABP, and increased IRS-2 protein levels in the liver. The muscarinic receptor antagonist atropine blocked these effects of physostigmine on liver TG, serum insulin, and hepatic protein levels of SREBP-1 and L-FABP. These results demonstrate that AChE inhibition facilitated fasting-induced TG accumulation with up regulation of the hepatic L-FABP and SREBP-1 in mice, at least in part via the activation of muscarinic acetylcholine receptors. Our studies highlight the crucial role of parasympathetic regulation in fasting-induced TG accumulation, and may be an important source of information on the mechanism of hepatic disorders of lipid metabolism.

Protective role of caffeic acid phenethyl ester on serum cholinesterase inhibition by acute exposure to diazinon in rats.

To evaluate whether caffeic acid phenethyl ester (CAPE), a flavonoid-like natural compound plentifully found in beeswax, has a protective effect on diazinon-induced serum cholinesterase (ChE) inhibition in rats. Animals were divided into 4 groups. The first animal group was not treated with any substance. The second animal group was orally given a 200 mg/kg body weight (bw) sublethal dose of diazinon. The third animal group was injected intraperitoneally with 2.84 mg (10 micromol)/kg bw of CAPE 1 day prior to administration of 200 mg/kg bw of diazinon orally. The fourth animal group was intraperitoneally injected with 2.84 mg (10 tmol)/kg bw of CAPE 30 min after 200 mg/kg bw of diazinon was orally administered. Analysis of the animal blood samples obtained 48 h after diazinon administration revealed that diazinon decreased serum ChE activity by 75%, while CAPE administration 24 h prior to and 30 min following diazinon application improved serum ChE activity by 25%-32% as compared to levels with diazinon administration only. In silico studies suggest that CAPE prevents diazinon from binding to butyryl ChE due to a higher binding affinity than that of diazinon. Our laboratory findings suggest that CAPE plays a protective role against butyryl ChE inhibition by diazinon.

Transferase activity of horse blood serum cholinesterase at hydrolysis of 1-methyl-8-acetoxychinolinium iodide in the presence of aliphatic alcohols

To check whether the horse blood serum butyrylcholinesterase expresses transferase activity at the complex ester hydrolysis in the presense of several low-molecular aliphatic alcohols, a study was performed with aid of the chromogenic substrate 1-methyl-8-acetoxychinolium whose phenolic hydrolysis product absorbs intensively at 445 nm, whereas the initial ester in this specter area practically does not absorb. This allowed measuring simultaneously the products of accumulation of both products of enzymatic hydrolysis: of acetic acid by the potentiometric, while of phenol--by the photometric method. Rates of formation of both products of enzymatic hydrolysis are practically equal in experiments with all studied alcohols. This indicates that horse blood serum butyrylcholinesterase under these experimental conditions does not catalize transfer of acetyl residue to the studied aliphatic alcohols, i. e. does not have transefase activity.

Low level chlorpyrifos exposure increases anandamide accumulation in juvenile rat brain in the absence of brain cholinesterase inhibition

The prevailing dogma is that chlorpyrifos (CPF) mediates its toxicity through inhibition of cholinesterase (ChE). However, in recent years, the toxicological effects of developmental CPF exposure have been attributed to an unknown non-cholinergic mechanism of action. We hypothesize that the endocannabinoid system may be an important target because of its vital role in nervous system development. We have previously reported that repeated exposure to CPF results in greater inhibition of fatty acid amide hydrolase (FAAH), the enzyme that metabolizes the endocannabinoid anandamide (AEA), than inhibition of either forebrain ChE or monoacylglycerol lipase (MAGL), the enzyme that metabolizes the endocannabinoid 2-arachidonylglycerol (2-AG). This exposure resulted in the accumulation of 2-AG and AEA in the forebrain of juvenile rats; however, even at the lowest dosage level used (1.0mg/kg), forebrain ChE inhibition was still present. Thus, it is not clear if FAAH activity would be inhibited at dosage levels that do not inhibit ChE. To determine this, 10 day old rat pups were exposed daily for 7 days to either corn oil or 0.5mg/kg CPF by oral gavage. At 4 and 12h post-exposure on the last day of administration, the activities of serum ChE and carboxylesterase (CES) and forebrain ChE, MAGL, and FAAH were determined as well as the forebrain AEA and 2-AG levels. Significant inhibition of serum ChE and CES was present at both 4 and 12h. There was no significant inhibition of the activities of forebrain ChE or MAGL and no significant change in the amount of 2-AG at either time point. On the other hand, while no statistically significant effects were observed at 4h, FAAH activity was significantly inhibited at 12h resulting in a significant accumulation of AEA. Although it is not clear if this level of accumulation impacts brain maturation, this study demonstrates that developmental CPF exposure at a level that does not inhibit brain ChE can alter components of endocannabinoid signaling.

Decline in serum cholinesterase activities predicts 2-year major adverse cardiac events.

Parasympathetic activity influences long-term outcome in patients with cardiovascular disease, but the underlying mechanism(s) linking parasympathetic activity and the occurrence of major adverse cardiovascular events (MACEs) are incompletely understood. The aim of this pilot study was to evaluate the association between serum cholinesterase activities as parasympathetic biomarkers and the risk for the occurrence of MACEs. Cholinergic status was determined by measuring the cumulative capacity of serum acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) to hydrolyze the AChE substrate acetylthiocholine. Cholinergic status was evaluated in randomly selected patients undergoing cardiac catheterization. The patients were divided into two groups of 100 patients in each group, with or without occurrence of MACEs during a follow-up period of 40 months. Cox regression models adjusted for potential clinical, metabolic and inflammatory confounders served to evaluate association with clinical outcome. We found that patients with MACE presented lower cholinergic status and AChE values at catheterization (1,127 ± 422 and 359 ± 153 nmol substrate hydrolyzed per minute per milliliter, respectively) than no-MACE patients (1,760 ± 546 and 508 ± 183 nmol substrate hydrolyzed per minute per milliliter, p < 0.001 and p < 0.001, respectively), whose levels were comparable to those of matched healthy controls (1,622 ± 303 and 504 ± 126 nmol substrate hydrolyzed per minute per milliliter, respectively). In a multivariate analysis, patients with AChE or total cholinergic status values below median showed conspicuously elevated risk for MACE (hazard ratio 1.85 [95% confidence interval [CI] 1.09-3.15, p = 0.02] and 2.21 [95% CI 1.22-4.00, p = 0.009]) compared with those above median, even after adjusting for potential confounders. We conclude that parasympathetic dysfunction expressed as reduced serum AChE and AChE activities in patients compared to healthy controls can together reflect impaired parasympathetic activity. This impairment predicts the risk of MACE up to 40 months in such patients. Monitoring these parasympathetic parameters might help in the risk stratification of patients with cardiovascular disease.

Paraoxonase activity and genetic polymorphisms in northern Han Chinese workers exposed to organophosphate pesticides

Paraoxonase (PON1) is one of the major players in the detoxification of organophosphates (OPs). This study presents our investigation into the effect of OPs on serum PON1 activity and the distribution of common PON1 polymorphisms in Han Chinese workers with repeated high exposure to OP pesticides, and the factors modulating PON1 activity. In all, 400 participants, including 180 workers exposed to OP pesticides occupationally, and 220 controls were investigated. Serum PON1 and cholinesterase (ChE) activity were measured, and genotyping was done using polymerase chain reaction-restriction fragment length polymorphism. The association between PON1 activity and PON1 polymorphisms, and the influencing factors of PON1 activity, were analyzed. The results revealed that repeated OP exposures significantly decreased serum PON1 and ChE activity (P< 0.05), although the exposed workers did not complain of health problems. Higher L and R allele frequencies for the L55M and Q192R polymorphisms of PON1 were observed. PON1 polymorphisms (especially the Q192R polymorphism) and pesticide exposures significantly affected serum PON1 activity in the study population. Therefore, the results of this investigation indicate PON1 polymorphisms and pesticide exposures may be important risk predictors for OP poisoning in the Han Chinese population, who display very high frequencies of the M allele and R allele for PON1 polymorphisms at the positions 55 and 192, respectively.