Cholinesterase Enzyme Activity Research Articles

Investigation of cholinesterase and α-glucosidase enzyme activities, and molecular docking and dft studies for 1,2-disubstituted cyclopentane derivatives with phenyl and benzyl units.

Six known products (4-9) were prepared from reaction of adipoyl chloride with 1,2,3-trimethoxybenzene according to the literature. From (2,3,4-trimethoxyphenyl)(2-(2,3,4-trimethoxyphenyl)cyclopent-1-en-1-yl)methanone (4) of them, four new 1,2-disubstituted cyclopentane derivatives (10-13) with phenyl and benzyl units were synthesized by reactions such as hydrazonation, catalytic hydrogenation and bromination. The obtained compounds 4-13 were examined for their in vitro inhibitory activity against acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and α-glucosidase enzymes. All compounds 4-13 showed inhibition at nanomolar level with Ki values in the range of 45.53 ± 7.35-631.96 ± 18.88nM for AChE, 84.30 ± 9.92-622.10 ± 35.14nM for BChE, and 25.47 ± 4.46-48.87 ± 7.33 for α-Glu. In silico molecular docking studies of the potent compounds were performed in the active sites of AChE (PDB: 1E66), BChE (PDB: 1P0I), and α-glucosidase (PDB: 5ZCC) to compare the effect of bromine atom on the inhibition mechanism. The optimized molecular structures, HOMO-LUMO energies and molecular electrostatic potential maps for the compounds were calculated by using density functional theory with B3LYP/6-31 + G(d,p).

New Charged Cholinesterase Inhibitors: Design, Synthesis, and Characterization.

Triazoles and triazolium salts are very common subunits in the structures of various drugs. Medicaments with a characteristic 1,2,3-triazole core are also being developed to treat neurodegenerative disorders associated with cholinesterase enzyme activity. Several naphtho- and thienobenzo-triazoles from our previous research emerged as being particularly promising in that sense. For this reason, in this research, new naphtho- and thienobenzo-triazoles 23-34, as well as 1,2,3-triazolium salts 44-51, were synthesized and tested. Triazolium salts 44-46 showed excellent activity while salts 47 and 49 showed very good inhibition toward both butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) enzymes. In contrast, neutral photoproducts were shown to be selective towards BChE but with very good inhibition potential as molecules 24-27. The representative of newly prepared compounds, 45 and 50, were stable in aqueous solution and revealed intriguing fluorimetric properties, characterized by a strong Stokes shift of >160 nm. Despite their condensed polycyclic structure shaped similarly to well-known DNA-intercalator ethidium bromide, the studied compounds did not show any interaction with ds-DNA, likely due to the unfavorable steric hindrance of substituents. However, the studied dyes bind proteins, particularly showing very diverse inhibition properties toward AChE and BChE. In contrast, neutral photoproducts were shown to be selective towards a certain enzyme but with moderate inhibition potential. The molecular docking of the best-performing candidates to cholinesterases' active sites identified cation-π interactions as the most responsible for the stability of the enzyme-ligand complexes. As genotoxicity studies are crucial when developing new active substances and finished drug forms, in silico studies for all the compounds synthesized have been performed.

Link of Serum Esterase Enzymes with Cognitive Impairment in Diabetic Patients

Cognitive impairment is one of the main complications of diabetes and patients with cognitive impairment are considered to be in an intermediate stage of decreased cognition with higher risk of developing dementia and Alzheimer's disease. This study aimed at evaluating serum activity of two esterase enzymes including cholinesterase and paraoxonase 1 (PON 1) in diabetic patients and association with cognitive performance and metabolic parameters. In this crosssectional study, 128 diabetic patients were enrolled. Cognitive performance was evaluated using the Wechsler Adult Intelligence Scale-Revised (WAIS-R). Body mass index, fasting blood glucose, fasting blood insulin, insulin resistance, serum cholinesterase and paraoxonase 1 activity were measured. Prevalence of cognitive impairment was found to be 77% in the study population. Serum cholinesterase activity was found to be higher in diabetic patients with cognitive impairment than the patients with normal cognitive performance (p < 0.04). Further, a negative correlation was found between cognitive performance and cholinesterase activity, albeit statistically non-significant. Alteration in the activity of cholinesterase enzyme was shown to be associated with cognitive impairment in diabetic patients and future studies are required to find the pathophysiological mechanisms of diabetic cognitive dysfunction.

Rationally Designed Functionalization of Single-Walled Carbon Nanotubes for Real-Time Monitoring of Cholinesterase Activity and Inhibition in Plasma.

Enzymes play a pivotal role in regulating numerous bodily functions. Thus, there is a growing need for developing sensors enabling real-time monitoring of enzymatic activity and inhibition. The activity and inhibition of cholinesterase (CHE) enzymes in blood plasma are fluorometrically monitored using near-infrared (NIR) fluorescent single-walled carbon nanotubes (SWCNTs) as probes, strategically functionalized with myristoylcholine (MC)- the substrate of CHE. A significant decrease in the fluorescence intensity of MC-suspended SWCNTs upon interaction with CHE is observed, attributed to the hydrolysis of the MC corona phase of the SWCNTs by CHE. Complementary measurements for quantifying choline, the product of MC hydrolysis, reveal a correlation between the fluorescence intensity decrease and the amount of released choline, rendering the SWCNTs optical sensors with real-time feedback in the NIR biologically transparent spectral range. Moreover, when synthetic and naturally abundant inhibitors inhibit the CHE enzymes present in blood plasma, no significant modulations of the MC-SWCNT fluorescence are observed, allowing effective detection of CHE inhibition. The rationally designed SWCNT sensors platform for monitoring of enzymatic activity and inhibition in clinically relevant samples is envisioned to not only advance the field of clinical diagnostics but also deepen further understanding of enzyme-related processes in complex biological fluids.

Fenpropathrin Induces Oxidative Stress, Inhibits Cholinesterase, and Causes Genotoxicity in <i>Pethia conchonius</i> (Hamilton, 1822)

Pesticide contamination in water bodies is a serious threat to aquatic organisms. Among the new generation pesticides, synthetic pyrethroids enter the aquatic environment from agricultural runoff and are more persistent in aquatic environment. In this study, we investigated the effect of fenpropathrin, a type II pyrethroid, on Pethia conchonius. The median lethal concentration for commercial formulation of fenpropathrin (Danitol®) was determined to be 2.43 μg/L. Based on the median lethal concentration, the fish were exposed to 1/5th (0.486 μg/L) and 1/10th (0.243 μg/L) of median lethal concentrations for 30 days. After the exposure period, antioxidant enzymes status (superoxide dismutase and catalase), oxidative stress parameters (lipid peroxidation and reduced glutathione) in brain, liver, and kidney, cholinesterase enzyme activity in brain and muscles, and incidences of micronucleus were evaluated. In the treatment groups, alteration in antioxidant enzyme levels were observed in brain, liver, and kidney. Lipid peroxidation, which is indicative of oxidative stress, was observed but did not show much variation. Reduced glutathione was also altered. Cholinesterase activity was significantly different in the brain tissues between control and treatment groups; however, no significant difference was observed between the cholinesterase activities of muscles in control and treatment groups. Micronucleus incidence in treatment groups was higher than that in the control. Our study indicates that fenpropathrin altered the antioxidative enzyme status, inhibited cholinesterase activity in brain, and exhibited potential genotoxic effects in the fish Pethia conchonius.

Literature Review: Impact of Organophosphate Pesticide Exposure on Cholinesterase Enzyme Activity and Associated Risk Factors for Poisoning, 2017-2020

Introduction: Organophosphate pesticides, which are used to control pests of crops, affect the nervous system by inhibiting the activity of cholinesterase enzymes in the body. This can be achieved by inhaling, eating, or applying it to the skin. This study research aims to determine the level of pesticide exposure that can inhibit the activity of the Cholinesterase enzyme in the blood. This study employed a systematic literature review with library sources used through Google Scholar and Science Direct, resulting in 16 research articles discussing cholinesterase enzyme activity due to exposure to organophosphates discussed in 2017-2020. Discussion: The results of a previous study found that exposure to organophosphates significantly reduced cholinesterase enzyme activity by 50-80%. Testing for cholinesterase as a biomarker of exposure to Organophospate (OP) through acetylcholinesterase activity in red blood cells (AChE). This study explored the relationship between gender, age, knowledge of farmers, personal protective equipment, farmers’ smoking behavior, and duration of spraying. Conclusion: Poisoning alters the activity of cholinesterase enzymes in the blood of farmers, resulting in acute and chronic health problems. Several factors have been found to correlate with organophosphate poisoning, including age, level of knowledge among farmers, use of personal protective equipment, smoking behavior, and duration of spraying activities.

Copper oxide nanoparticles exhibit variable response against enzymatic toxicity biomarkers of Moina macrocopa.

Growing toxicity of nanomaterials to aquatic organisms is a major area of concern as it is destroying the carefully evolved aquatic ecosystem and food web. Copper oxide nanoparticles (CuONPs) are among the top industrially manufactured nanomaterials having multifaceted applications in medicine, agriculture, energy, water technology, and other areas. However, reports on detailed scientific understanding behind toxic effects of CuONPs on aquatic organisms are scant. The present work reports on the interaction of CuONPs of 10 ± 05nm with an ecologically significant aquatic species, Moina macrocopa, at morphological and enzymatic levels. CuONPs were found to be severely toxic just within 48h of exposure as seen from the lethal value (48h LC50) of 0.137 ± 0.002ppm. Profiling of enzymatic toxicity biomarkers indicated variable response of CuONPs on selected enzymes of M. macrocopa at two sub-lethal concentrations (0.013 to 0.039ppm). While the activities of acetyl cholinesterase and digestive enzymes (trypsin, amylase) were found to be significantly (p < 0.001) lowered after exposure to CuONPs, the β-galactosidase activity was completely inhibited. Among the antioxidant enzymes that were assayed, superoxide dismutase and glutathione-S-transferase activity was found to increase (p > 0.001), while that of catalase decreased (p > 0.001, < 0.05) with increase in exposure to CuONPs. An upsurge of several folds was seen in the activity of alkaline phosphatase after exposure to CuONPs as compared to the control group. CuONPs accumulated in the gut region of M. macrocopa which provided an ideal environment for CuONP to interact and alter the enzymes inM. macrocopa. This report highlights the use of enzymes as sensitive biomarker to detect toxicity of trace amount of CuONPs in a very sensitive non-target crustacean species found in water bodies.

Effect of alkaloid extract from Andrographis paniculata (Burm. f.) Nees and Phyllanthus amarus Schumach. & Thonn. on cognitive related biochemicals in the brain of streptozotocin-induced diabetic rats

IntroductionDiabetes mellitus (DM) is a chronic metabolic disorder linked to cognitive impairment and memory deficit, known as diabetes encephalopathy. This study examined the anti-diabetic and neuroprotective effects of alkaloid extracts from Andrographis paniculata (A. paniculata) and Phyllanthus amarus (P. amarus) leaves, a Traditional Chinese Medicine, on carbohydrate-metabolizing (α-amylase and α-glucosidase) enzyme, cholinesterase and purinergic enzyme activities, and antioxidants in the brains of streptozotocin (STZ)-induced diabetic rats. MethodsThe alkaloid extraction of A. paniculata and P. amarus was done. Male Wistar rats were divided into seven groups (n = 5) and were made diabetic by intraperitoneal injection of 50 mg/kg of STZ except Group I, which received saline (normal control). Group II-untreated diabetic rats (diabetic control), Group III-diabetic rats received 5 mg/kg Glibenclamide (standard drug); Group IV and V received 5 and 50 mg/kg P. amarus respectively; and Group VI and VII received 5 and 50 mg/kg A. paniculata, respectively. ResultsThe results showed that the elevated blood glucose and redox makers levels and enzyme activities were significantly increased in the untreated diabetic rats. Reduced antioxidant biomolecules (enzymatic and non-enzymatic antioxidant) levels were also observed. However, these were considerably ameliorated upon treatment with the alkaloid extracts in a dose-dependent manner. ConclusionThe study found that the alkaloid extract of P. amarus and A. paniculata leaves can modulate cognitive functioning and antioxidant profile in STZ-induced diabetic rats, suggesting it could be a promising alternative for managing diabetes and its complications, including cognitive impairment, in the treatment of diabetes and diabetes encephalopathy.

Literature Study: Overview of Cholinesterase Enzyme Activity in Horticultural Farmers Exposed to Organophosphates and Carbamates

Pesticides are chemicals used to control pests and animals that cause damage to crops. Organophosphate and carbamate pesticides have the potential to cause poisoning for humans, including horticultural farmers. Farmers who experience poisoning will experience metabolic disorders of the enzyme cholinesterase in the blood. To determine the activity of the enzyme cholinesterase due to exposure to organophosphates and carbamates can use the Tintometer kit and Spectrophotometer. This scientific paper is made with a literature study method that discusses cholinesterase enzyme activity in horticultural farmers based on internal factors including gender, age, and knowledge then external factors including spraying frequency, working period, use of PPE, and length of spraying. This literature study used 18 journals in the publication year 2013 - 2023. Based on the results of the journal literature review, the danger of pesticide poisoning which results in a decrease in the activity of the enzyme cholinesterase in the blood of farmers will increase the longer farmers are exposed to organophosphate and carbamate pesticides. The decrease in cholinesterase enzyme activity in horticultural farmers based on internal factors in farmers with age, gender, and low knowledge level. For external factors, there was a decrease in cholinesterase enzyme activity in farmers with a spraying frequency of &gt;2 times a week, a working period of more than 5 years, farmers who used incomplete PPE and farmers who sprayed pesticides for more than 3 hours per day. Keywords: Organophosphate, Carbamate, Enzim Cholinesterase

Effects of fluoride on oxidative DNA damage, nitric oxide level, lipid peroxidation and cholinesterase enzyme activity in a rotenone-induced experimental Parkinson’s model

ABSTRACT Objective Environmental toxins are known to be one of the important factors in the development of Parkinson’s disease (PD). This study was designed to investigate the possible contribution of fluoride (F) exposure to oxidative stress and neurodegeneration in rats with PD induced by rotenone (ROT). Materials and methods A total of 72 Wistar albino male rats were used in the experiment and 9 groups were formed with 8 animals in each group. ROT (2 mg/kg) was administered subcutaneously (sc) for 28 days. Different doses of sodium fluoride (NaF) (25, 50 and 100 ug/mL) were given orally (po) for 4 weeks. Malondialdehyde (MDA), glutathione (GSH), nitric oxide (NO), oxidative DNA damage (8-OHdG) and cholinesterase (AChE/BChE) enzyme activities were evaluated in serum and brain tissue homogenates. Results Rats treated with ROT and NaF had significant increases in serum and brain MDA, NO content, and decreases in GSH. In addition, the combination of ROT and NaF triggered oxidative DNA damage and resulted in increased AChE/BChE activity. Conclusions Findings suggest that NaF and ROT may interact synergistically leading to oxidative damage and neuronal cell loss. As a result, we believe that exposure to pesticides in combination with NaF is one of the environmental factors that should not be ignored in the etiology of neurological diseases such as PD in populations in areas with endemic fluorosis.

Modulatory effects of Cannabis sativa co-administration with tramadol and codeine on cognitive function in male rats

Most teenagers mix up various psychoactive cocktail substances in combinations to get intoxicated. The role of the mixture combination of codeine (CDE), tramadol (TMD), and Cannabis sativa (CNB) on brain cognition, purinergic, cholinergic, and antioxidant enzyme activities remains unknown. This study sought to assess the mechanism of action of combinations of CDE+ TMD+ CNB on the function and activities of the brain of male Wistar rats. Forty-eight male Wistar rats were divided into 8 groups, n = 6. Group 1 served as a control, groups 2, 3, and 4 were exposed to CDE (2 mg/kg bw), TMD (10 mg/kg bw), and CNB (200 mg/kg bw), while groups 5, 6, 7, and 8 were co-administered with CDE+TMD, CNB+ TMD, CNB+CDE, and CNB+TMD+CDE orally for 28 days. This study revealed the effect of prolonged administration of CNB, TMD, and CDE on the suppression of cognitive function, acetyl-cholinesterase (AChE), butyl-cholinesterase (BChE), monoamine oxidase (MAO) enzyme activities, and antioxidant enzyme activities in rats’ brains when compared against control rats (P < 0.05). However, the activities of ectonucleosides (NTPdase), adenosine deaminase (ADA), and malondialdehyde levels produced in the brain of rats were significantly elevated (P < 0.05). This study reported the mechanism behind the neurotoxicity of CNB, TMD, and CDE on rats’ cognitive, cholinergic, purinergic, and antioxidant enzymes as a consequence of the drastic reduction in cholinesterase enzyme activities leading to neurotransmitter poisoning.

Determination of Constituents of Extract of Celtis tournefortii Lam. by LC-MS/MS, Investigation of Enzyme Inhibition, Antimicrobial and Anticancer Effects

Phytochemicals found in extracts obtained from plants are very important bioactive constituents. In this study, phytochemicals in extract content obtained from Celtis tournefortii .Lam. tree (CT) leaves were determined by a LC-MS method. The constituents with the major concentrations was found rutin (2479.89 µg ml-1), coumarin (1241.68 µg ml-1), biochanin A (1026.42 µg ml-1), shikimic acid (477.32 µg ml-1), chlorogenic acid (300.76 µg ml-1). The suppressive effects of CT extract on the growth of pathogenic strains were studied by microdilution method. It was observed that it caused suppression on the strains in the concentration range of 2.00-8.00 µg ml-1. The inhibition effects of the extract on acetyl cholinesterase and glutathione-S transferase enzyme activities were investigated, and 50% inhibitory values of enzyme activity were found to be 13.58 and 13.86, respectively. Using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay method, the cell viability suppressive effects of CT leaf extract were studied in healthy skin fibroblast cells as well as ovarian, colon and brain cancer cells. It was observed that they created a 42%, 4.27%, and 14.29% suppression in cells, respectively.

Assessment of exposure to pesticides and the knowledge, attitude and practice among farmers of western Bhutan.

An estimated 69% of the population of Bhutan is engaged in agriculture. Farmers are exposed to a wide variety of pesticides during the preparation, transport, storage, mixing and application of pesticides posing a significant health risk. A controlled cross-sectional study of farmers in selected sites of Bhutan was conducted to characterize the level of exposure to pesticides and assess their knowledge attitude and practice on the safe handling of pesticides. A total of 399 participants were enrolled in the study comprising of 295 exposed farmers and 104 healthy and unexposed controls. A structured investigator administered questionaries was used to assess their Knowledge, Attitude and practice, and their blood samples were taken for measuring Acetyl Cholinesterase enzyme activity level. There was a significant difference between the Acetyl Cholinesterase enzyme inhibition of exposed and non-exposed control groups observed in the study (P < 0.001). Of the total of 295 farmers, 62 (21.01%) had severe enzyme inhibition of >30% as compared to the unexposed group. Safety practices of handling pesticides were low. The most common symptoms self-reported were headache (OR 1.08, 0.60-1.93) and neurological problems like forgetfulness, lack of concentration (OR 1.12, 0.50-2.48) and increased tiredness (OR 1.075, 0.52-2.19) that were significantly associated with the enzyme inhibition. In addition, we record a very low level of knowledge (17.0%), a fair attitude (63.0%) and poor practice (35.0%) on the safe handling and management of pesticides. This pilot study provides indication of exposure to pesticides in the selected sites of the country. Furthermore, it provides evidence for public health interventions by identifying the exposure patterns and pathways of individuals most at risk in the farming communities of the country. Surveillance and bio-monitoring programs are deemed necessary.

Gallic acid abates cadmium chloride toxicity via alteration of neurotransmitters and modulation of inflammatory markers in Wistar rats

Cadmium is a highly neurotoxic heavy metal that disrupts membranes and causes oxidative stress in the brain. The study aimed to investigate the neuroprotective effect of gallic acid on oxidative damage in the brains of Wistar rats exposed to cadmium chloride (CdCl2). Male Wistar rats were divided into four groups of five rats each. Group 1 was administered distilled water only throughout the study. Throughout the study, Group 2 received CdCl2 alone (5 mg/kg b.w./day), Group 3 received gallic acid (20 mg/kg b.w./day), and Group 4 received CdCl2 + gallic acid (20 mg/kg). Treatments were oral with distilled water as a vehicle. The study lasted 21 days. In the brain, the activities of cholinesterase and antioxidant enzymes were evaluated, as well as the levels of reduced glutathione, malondialdehyde, neurotransmitters, Na+/K+ ATPase, myeloperoxidase activity, nitric oxide, and interleukin-6. CdCl2-induced brain impairments in experimental animals and gallic acid prevents the following CdCl2-induced activities: inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), elevated neurotransmitters (serotonin and dopamine), decreased antioxidant enzymes (superoxide dismutase, catalase), decreased glutathione, Na+/K+ ATPases, and increased MDA and neuroinflammatory markers (myeloperoxidase (MPO), nitric oxide, and interleukin-6 in the brain of experimental rats exposed to CdCl2 (p < 0.05). Taken together, the neuroprotective effects of gallic acid on CdCl2-induced toxicity in the brains of rats suggest its potent antioxidant and neurotherapeutic properties.

Stigmasterol- an Acetylcholinesterase Inhibitor from Phormidium retzii with relevance to Alzheimer's disease Therapy.

This study observed in vitro screening, purification and identification of cholinesterase inhibitors from the microalgae Phormidium retzii. Mixed microalgal culture was screened from freshwater samples for Phormidium sp. Single colony was purified and authenticated as P. retzii. Acetylcholinesterase (AChE) enzyme was purified from hRBC ghost. Sequential extraction of P. retzii was performed using organic solvents. Cholinesterase enzyme activity and its inhibition by various extracts were then tested. The active fractions were then subjected to partial purification and characterization. Petroleum ether extract of P. retzii showed maximum inhibition of 68.6 % against AChE while other solvent extracts showed no inhibition. Seven fractions were obtained from the active extract using thin layer chromatography. Among which fraction no. 5 showed maximum inhibition of 86.37 % towards AChE. Fraction no. 5 when subjected to GC-MS led to determination of the active principle as stigmasterol. The maximum inhibition of stigmasterol (0.45µM) was 81.2±0.08% with IC50 value of 0.214. Stigmasterol from P. retzii inhibited AChE projecting itself as safer drug for Alzheimer's disease with minimal side effects.

Fenugreek seed powder protects mice against arsenic-induced neurobehavioral changes

The current study was designed to evaluate the protective effect of fenugreek seed powder against As-induced neurobehavioral and biochemical perturbations using a mouse model. Mice exposed to arsenic at 10 mg/kg body weight showed development of anxiety-like behavior and memory impairment compared to control mice in elevated plus maze and Morris water maze tests, respectively. A significantly decreased acetyl and butyrylcholinesterase, superoxide dismutase and glutathione reductase activities and brain-derived neurotrophic factor levels were found in the brain of arsenic-exposed mice compared to control mice. Interestingly, supplementation of fenugreek seed powder to arsenic-treated mice significantly restored the activity of cholinesterase and antioxidant enzymes (e.g. superoxide dismutase, glutathione reductase) as well as brain-derived neurotrophic factor levels in the brain tissue of arsenic-exposed mice. Consequently, reduced anxiety-like behavior, improved learning and memory were observed in fenugreek supplemented arsenic treated mice compared to only arsenic-exposed mice group. Thus, this study suggests that fenugreek seed powder reduces arsenic-induced neurotoxicity in mice.

Reproductive and developmental toxicity following exposure to organophosphate ester flame retardants and plasticizers, triphenyl phosphate and isopropylated phenyl phosphate, in Sprague Dawley rats.

Two organophosphate esters used as flame retardants and plasticizers, triphenyl phosphate (TPHP) and isopropylated phenyl phosphate (IPP), have been detected in environmental samples around the world. Human exposure primarily occurs via oral ingestion with reported higher concentrations in children. Currently, there are no data to evaluate potential risk from exposure to either TPHP or IPP during fetal development. These short-term perinatal studies in rats provide preliminary toxicity data for TPHP and IPP, including information on transfer to fetus/offspring and across the pup blood-brain barrier. In separate experiments, TPHP or IPP were administered via dosed feed at concentrations 0, 1000, 3000, 10 000, 15 000, or 30 000 ppm to time-mated Hsd:Sprague Dawley SD rats from gestation day (GD) 6 through postnatal day (PND) 28; offspring were provided dosed feed at the same concentration as their dam (PND 28-PND 56). TPHP- and IPP-related toxicity resulted in removal of both 30 000 ppm groups on GD 12 and 15 000 ppm IPP group after parturition. Body weight and organ weights were impacted with exposure in remaining dams. Reproductive performance was perturbed at ≥10 000 ppm TPHP and all IPP exposure groups. In offspring, both TPHP- and IPP-related toxicity was noted in pups at ≥10 000 ppm as well as reduction in bodyweights, delays in pubertal endpoints, and/or reduced cholinesterase enzyme activity starting at 1000 ppm TPHP or IPP. Preliminary internal dose assessment indicated gestational and lactational transfer following exposure to TPHP or IPP. These findings demonstrate that offspring development is sensitive to 1000 ppm TPHP or IPP exposure.

Hubungan Usia dan Status Gizi dengan Enzim Cholinesterase pada Pekerja Industri Pembuatan Bahan Baku Cat di Surabaya

The additive is one component of paint that inhibits the growth of bio-organisms in the finished paint product with pesticide-like properties. Workers in the manufacture of paints are one of the populations that are at risk of being exposed to heavy metals and pesticides, which enter the workers through inhalation for a long time continuously. The purpose of this study was to determine whether there was a relationship between the age of workers and the nutritional status of the Cholinesterase enzyme in workers in one of the paint raw material industries in Surabaya. This study used a cross-sectional study design with a sample of 89 workers. The variables in this study were age, nutritional status values as measured by BMI values, and cholinesterase enzyme activity. The correlation test results using a nonparametric test, namely the Spearman correlation test. The correlation results show no significance between age and CHE levels (p-value=0.376) and that there is a relationship between BMI and CHE levels (p-value=0.003). It is recommended for future researchers to add research variables including the influence of the length of work, work habits including smoking habits and exercise as well as the use of Personal Protective Equipment (PPE) while working.

Association between cholinesterase activity and critical illness brain dysfunction

BackgroundDelirium is a frequent manifestation of acute brain dysfunction and is associated with cognitive impairment. The hypothesized mechanism of brain dysfunction during critical illness is centered on neuroinflammation, regulated in part by the cholinergic system. Point-of-care serum cholinesterase enzyme activity measurements serve as a real-time index of cholinergic activity. We hypothesized that cholinesterase activity during critical illness would be associated with delirium in the intensive care unit (ICU) and cognitive impairment after discharge.MethodsWe enrolled adults with respiratory failure and/or shock and measured plasma acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity on days 1, 3, 5, and 7 after enrollment. AChE values were also normalized per gram of hemoglobin (AChE/Hgb). We assessed for coma and delirium twice daily using the Richmond Agitation Sedation Scale and the Confusion Assessment Method for the ICU to evaluate daily mental status (delirium, coma, normal) and days alive without delirium or coma. Cognitive impairment, disability, and health-related quality of life were assessed at up to 6 months post-discharge. We used multivariable regression to determine whether AChE, AChE/Hgb, and BChE activity were associated with outcomes after adjusting for relevant covariates.ResultsWe included 272 critically ill patients who were a median (IQR) age 56 (39–67) years and had a median Sequential Organ Failure Assessment score at enrollment of 8 (5–11). Higher daily AChE levels were associated with increased odds of being delirious versus normal mental status on the same day (Odds Ratio [95% Confidence Interval] 1.64 [1.11, 2.43]; P = 0.045). AChE/Hgb and BChE activity levels were not associated with delirious mental status. Lower enrollment BChE was associated with fewer days alive without delirium or coma (P = 0.048). AChE, AChE/Hgb, and BChE levels were not significantly associated with cognitive impairment, disability, or quality of life after discharge.ConclusionCholinesterase activity during critical illness is associated with delirium but not with outcomes after discharge, findings that may reflect mechanisms of acute brain organ dysfunction.Trial Registration: NCT03098472. Registered 31 March 2017.

Recent Progress in Research on Mechanisms of Action of Natural Products against Alzheimer's Disease: Dietary Plant Polyphenols.

Alzheimer's disease (AD) is an incurable degenerative disease of the central nervous system and the most common type of dementia in the elderly. Despite years of extensive research efforts, our understanding of the etiology and pathogenesis of AD is still highly limited. Nevertheless, several hypotheses related to risk factors for AD have been proposed. Moreover, plant-derived dietary polyphenols were also shown to exert protective effects against neurodegenerative diseases such as AD. In this review, we summarize the regulatory effects of the most well-known plant-derived dietary polyphenols on several AD-related molecular mechanisms, such as amelioration of oxidative stress injury, inhibition of aberrant glial cell activation to alleviate neuroinflammation, inhibition of the generation and promotion of the clearance of toxic amyloid-β (Aβ) plaques, inhibition of cholinesterase enzyme activity, and increase in acetylcholine levels in the brain. We also discuss the issue of bioavailability and the potential for improvement in this regard. This review is expected to encourage further research on the role of natural dietary plant polyphenols in the treatment of AD.