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Molecules (Basel, Switzerland) Aug 2018Commercially available pesticides were examined as and acetylcholinesterase (AChE and AChE) inhibitors by means of ligand-based (LB) and structure-based (SB) in silico...
The Targeted Pesticides as Acetylcholinesterase Inhibitors: Comprehensive Cross-Organism Molecular Modelling Studies Performed to Anticipate the Pharmacology of Harmfulness to Humans In Vitro.
Commercially available pesticides were examined as and acetylcholinesterase (AChE and AChE) inhibitors by means of ligand-based (LB) and structure-based (SB) in silico approaches. Initially, the crystal structures of simazine, monocrotophos, dimethoate, and acetamiprid were reproduced using various force fields. Subsequently, LB alignment rules were assessed and applied to determine the inter synaptic conformations of atrazine, propazine, carbofuran, carbaryl, tebufenozide, imidacloprid, diuron, monuron, and linuron. Afterwards, molecular docking and dynamics SB studies were performed on either AChE or AChE, to predict the listed pesticides' binding modes. Calculated energies of global minima () and free energies of binding (∆) were correlated with the pesticides' acute toxicities (i.e, the LD values) against mice, as well to generate the model that could predict the LDs against humans. Although for most of the pesticides the low correlates with the high acute toxicity, it is the ∆ that conditions the LD values for all the evaluated pesticides. Derived = (∆) AChE model may predict the against AChE, too. The AChE inhibition by atrazine, propazine, and simazine (the most toxic pesticides) was elucidated by SB quantum mechanics (QM) DFT mechanistic and concentration-dependent kinetic studies, enriching the knowledge for design of less toxic pesticides.
Topics: Acetylcholinesterase; Animals; Cholinesterase Inhibitors; Humans; Kinetics; Molecular Conformation; Molecular Docking Simulation; Molecular Dynamics Simulation; Molecular Structure; Pesticides; Quantitative Structure-Activity Relationship; Solutions; Structure-Activity Relationship
PubMed: 30200244
DOI: 10.3390/molecules23092192 -
Journal of Insect Science (Online) Feb 2014The toxicological and biochemical characteristics of acetylcholinesterases (AChE) in nine populations of the common pistachio psyllid, Agonoscena pistaciae Burckhardt...
The toxicological and biochemical characteristics of acetylcholinesterases (AChE) in nine populations of the common pistachio psyllid, Agonoscena pistaciae Burckhardt and Lauterer (Hemiptera: Psyllidae), were investigated in Kerman Province, Iran. Nine A. pistaciae populations were collected from pistachio orchards, Pistacia vera L. (Sapindales: Anacardiaceae), located in Rafsanjan, Anar, Bam, Kerman, Shahrbabak, Herat, Sirjan, Pariz, and Paghaleh regions of Kerman province. The previous bioassay results showed these populations were susceptible or resistant to phosalone, and the Rafsanjan population was most resistant, with a resistance ratio of 11.3. The specific activity of AChE in the Rafsanjan population was significantly higher than in the susceptible population (Bam). The affinity (K(M)) and hydrolyzing efficiency (Vmax) of AChE on acetylthiocholine iodide, butyrylthiocholine iodide, and propionylthiocholine odide as artificial substrates were clearly lower in the Bam population than that in the Rafsanjan population. These results indicated that the AChE of the Rafsanjan population had lower affinity to these substrates than that of the susceptible population. The higher Vmax value in the Rafsanjan population compared to the susceptible population suggests a possible over expression of AChE in the Rafsanjan population. The in vitro inhibitory effect of several organophosphates and carbamates on AChE of the Rafsanjan and Bam populations was determined. Based on I50, the results showed that the ratios of AChE insensitivity of the resistant to susceptible populations were 23 and 21.7-fold to monocrotophos and phosphamidon, respectively. Whereas, the insensitivity ratios for Rafsanjan population were 0.86, 0.8, 0.78, 0.46, and 0.43 for carbaryl, eserine, propoxur, m-tolyl methyl carbamate, and carbofuran, respectively, suggesting negatively correlated sensitivity to organophosphate-insensitive AChE. Therefore, AChE from the Rafsanjan population showed negatively correlated sensitivity, being insensitive to phosphamidon and monocrotophos and sensitive to N-methyl carbamates.
Topics: Acetylcholinesterase; Acetylthiocholine; Animals; Butyrylthiocholine; Hemiptera; Insecticide Resistance; Insecticides; Iran; Organothiophosphorus Compounds; Thiocholine
PubMed: 25373165
DOI: 10.1093/jis/14.1.18 -
PloS One 2020The fungal toxin acts as effective, low-cost chemical substances for pest control worldwide and also an alternative to synthetic insecticides. This study assessed the...
BACKGROUND
The fungal toxin acts as effective, low-cost chemical substances for pest control worldwide and also an alternative to synthetic insecticides. This study assessed the larvicidal potential of Metarhizium anisopliae fungi derived metabolites against Aedes aegypti, Anopheles stephensi, Culex quinquefasciatus and non-targeted organisms at 24hr post treatment.
METHOD
Isolation of entomopathogenic fungi M. anisopliae from natural traps confirmed by using 18s rDNA biotechnological tools. Crude extracts from M. anisopliae solvent extraction and their secondary metabolites were bio-assayed following WHO standard procedures against Ae. aegypti, An. stephensi and Cx. quinquefasciatus, Artemia nauplii, Eudrilus eugeniae, and Solanum lycopersicum after 24 hr exposure. Histopathological analysis of E. eugeniae treated with fungi metabolites toxicity compared to those treated with Monocrotophos after 24hrpost-treatment. M. anisopliae metabolites were characterized using GC-MS and FT-IR analysis.
RESULTS
The larvicidal activity was recorded in highest concentration of 75μg/ml, with 85%, 97% and 89% mortality in Ae. aegypti, An. stephensi and Cx. quinquefasciatus respectively. M. anisopliae metabolites produced LC50 values in Ae. aegypti, 59.83μg/ml, in An. stephensi, 50.16μg/ml and in Cx. quinquefasciatus, 51.15μg/ml respectively. M. anisopliae metabolites produced lower toxic effects on A. nauplii, LC50 values were, 54.96μg/ml respectively. Bio-indicator toxicity results show 18% and 58% mortality was recorded in E. eugeniae and A. nauplii and also there is no phytotoxicity that was observed on S. lycopersicum L. under semi-field condition. E. eugeniae histopathological studies shows fungal metabolites showed lower sub-lethal effects compared to synthetic chemical pesticide at 24hrs of the treatment. The GC-MS and FT-IR analysis identified five major components of active ingredients.
CONCLUSION
Findings of this study indicate that, M. anisopliae ethyl acetate derived secondary metabolites are effective against larvae of Ae. aegypti, An. stephensi and Cx. quinquefasciatus mosquito species, lower toxicity effects were observed on non-target organisms such as, Artemia nauplii, Eudrilus eugeniae as well as, no toxicity effect were observed on Solanum lycopersicum. Further research should be conducted in laboratory for separation of single pure molecule and be tested semifield conditions.
Topics: Aedes; Animals; Anopheles; Biological Products; Culex; DNA, Fungal; DNA, Ribosomal; Gas Chromatography-Mass Spectrometry; Insect Control; Larva; Metarhizium; Monocrotophos; RNA, Ribosomal, 18S; Secondary Metabolism; Spectroscopy, Fourier Transform Infrared
PubMed: 32365106
DOI: 10.1371/journal.pone.0232172 -
Frontiers in Public Health 2022The present interventional study aimed to assess the impact of micronutrient supplementation on pesticide-residues concentrations, vitamins, minerals,...
The present interventional study aimed to assess the impact of micronutrient supplementation on pesticide-residues concentrations, vitamins, minerals, acetylcholinesterase activity and oxidative stress among 129 farm children (9-12 years, = 66 and 13-15 years, = 63) involved in farming activities in Ranga Reddy district, Telangana, India. Our data showed the presence of five organophosphorus pesticide residues (chlorpyrifos, diazinon, malathion, monocrotophos, and phosalone) among children before-supplementation (both age-groups); while post-supplementation, only two pesticide residues (chlorpyrifos and diazinon) were detected indicating improved metabolic rate. Vitamin E, copper, magnesium and zinc levels were also improved in both the age-groups and manganese levels were significantly increased only among children of 13-15 years age group. Further, post-supplementation also showed an improvement in acetylcholinesterase activity and a decrease in lipid peroxidation among both the age groups of children. However, further research for ascertaining the ameliorating effect of micronutrients in preventing adverse effects of organophosphorus pesticides must be conducted.
Topics: Acetylcholinesterase; Adolescent; Child; Chlorpyrifos; Diazinon; Dietary Supplements; Farms; Humans; Micronutrients; Organophosphorus Compounds; Oxidative Stress; Pesticide Residues; Pesticides
PubMed: 35774575
DOI: 10.3389/fpubh.2022.872125 -
Toxicology International May 2013Inducible expressions cytochrome P450s (CYPs) against environmental chemicals in brain tissues of experimental animals is well-documented. However, the precise role of...
Inducible expressions cytochrome P450s (CYPs) against environmental chemicals in brain tissues of experimental animals is well-documented. However, the precise role of specific brain cell type in the metabolism of different class of xenobiotics has not been explored adequately. We study the expression of selected CYPs (1A1/1A2, 2B1/2B2, 2E1) in primary cultures of rat brain neuronal and glial cell exposed to an organophosphate pesticide-monocrotophos (MCP), a known neurotoxicant. The cultured neurons and glial cells express significant expression of CYP1A1, 2B2 and 2E1 isoenzymes, where the levels were comparatively higher in neuronal cells. Neuronal cells exhibited greater induction of CYP2E1 against MCP exposure, while glial cells were having more vulnerability for CYP1A and 2B isoenzymes. Similarly, cells were showing substrate specific responses against the specific inducers of CYPs, that is, ethanol (2E1), cyclophosphamide (2B1/2B2), 3-methylcholanthrene (1A1/1A2). The altered expression and activity of selected CYPs in cultured neuronal and glial cells could be helpful in explaining the association between MCP-induced neurotoxicity/metabolism and synthesis or transport of the neurotransmitters. The induction of CYPs in glial cells may also have significance as these cells are thought to be involved in protecting the neurons from environmental insults and safeguard them from toxicity. The differential expression pattern of CYPs in neuronal and glial cells exposed to MCP also indicate the selective sensitivity of these cells against the xenobiotics, hence suggested their suitability as tool to screen neurotoxicity potential of variety of xenobiotics.
PubMed: 24082512
DOI: 10.4103/0971-6580.117264 -
Indian Journal of Critical Care... Feb 2024Organophosphorus (OP) and carbamate poisoning are significant concerns in developing nations. This study evaluates the effectiveness of the ChE check mobile, a...
BACKGROUND
Organophosphorus (OP) and carbamate poisoning are significant concerns in developing nations. This study evaluates the effectiveness of the ChE check mobile, a cholinesterase-rapid bedside diagnostic test, in the diagnosis and management of OP and carbamate poisoning.
MATERIALS AND METHODS
We conducted this prospective observational study, involving patients with OP and carbamate poisoning over 1 year (June 2016 to June 2017) at a single tertiary care center. Levels of RBC cholinesterase (E-AChE), butyl cholinesterase (BChE), and various other determinants were systematically coded and analyzed.
RESULTS
The study population ( = 60) consisted primarily of males ( = 43; 71.7%), with a mean age of 30.6 (SD: 13.7) years. Monocrotophos ( = 10; 20.4%) and carbofuran ( = 4; 8.1%) were the commonest OP and carbamate compounds, respectively. The median initial atropinization dose was 10 (: 0, 61.5) mg, with a median total administered atropine dose of 116 (IQR: 32, 320) mg. A significant negative correlation was found between E-AChE levels and both the initial atropinization dose (: -0.653, -value < 0.001) and total atropine requirement (: -0.659, -value < 0.001) during admission. An E-AChE cut-off of 4 units/g hemoglobin provided an area under the curve of 0.73 (sensitivity: 80.0%, specificity: 68.6%, -value < 0.001) for predicting moderate to severe peradeniya organophosphorus poisoning.
CONCLUSION
The check mobile device can be a valuable tool for prognosticating patients. There was a significant correlation between low E-AChE levels and the atropine requirement and severity.
HOW TO CITE THIS ARTICLE
Jha A, Hazra D, Yadav B, Zachariah A, Alex R. Prognostication and Prediction of Outcomes in Patients with Organophosphorus and Carbamate Poisoning: A Prospective Cohort Study. Indian J Crit Care Med 2024;28(2):141-147.
PubMed: 38323266
DOI: 10.5005/jp-journals-10071-24617 -
Cureus May 2023Organophosphates, also known as phosphate esters, are a category of pesticide compounds that function by indirectly inhibiting the activity of an enzyme called...
Organophosphates, also known as phosphate esters, are a category of pesticide compounds that function by indirectly inhibiting the activity of an enzyme called acetylcholinesterase (AChE). AChE is responsible for breaking down acetylcholine (ACh) at the neuromuscular junction into acetic acid and choline. These compounds cause various clinical presentations upon acute toxicity, among which intermediate syndrome (IMS) exhibits an unpredictable course. This report describes the case of a farmer who ingested monocrotophos and ethanol in a suicide attempt, leading to a prolonged stay in the hospital and invasive ventilation, along with complications including ventilator-associated pneumonia. The patient received a total of 9000 mg of atropine over his 14-day hospitalization period.
PubMed: 37362485
DOI: 10.7759/cureus.39368 -
Antioxidants (Basel, Switzerland) Dec 2021Oxidative stress-mediated tissue damage is primarily involved in hepatic injuries and dysfunctioning. Natural antioxidants have been shown to exert hepatoprotective,...
Oxidative stress-mediated tissue damage is primarily involved in hepatic injuries and dysfunctioning. Natural antioxidants have been shown to exert hepatoprotective, anti-inflammatory and antiapoptotic properties. The present study evaluated the effect of -acetylcysteine (NAC) against monocrotophos (MCP) exposure-induced toxicity in the rat liver. Albino Wistar rats were divided into four groups: (1) control, (2) NAC-treated, (3) MCP-exposure, (4) NAC and MCP-coexposure group. The dose of MCP (0.9 mg/kg b.wt) and NAC (200 mg/kg b.wt) were administered orally for 28 days. Exposure to MCP caused a significant increase in lipid peroxidation, protein oxidation and decreased glutathione content along with the depletion of antioxidant enzyme activities. Further MCP exposure increased pro-inflammatory cytokines levels and upregulated Bax and Caspase-3 expressions. MCP exposure also caused an array of structural alternations in liver tissue, as depicted by the histological and electron microscopic analysis. Thepretreatment of NAC improved glutathione content, restored antioxidant enzyme activities, prevented oxidation of lipids and proteins, decreased pro-inflammatory cytokines levels and normalized apoptotic protein expression. Treatment of NAC also prevented histological and ultrastructural alternations. Thus, the study represents the therapeutic efficacy and antioxidant potential of NAC against MCP exposure in the rat liver.
PubMed: 35052593
DOI: 10.3390/antiox11010090 -
Cureus Jun 2023Background Organophosphorus (OP) compound poisoning is the most common toxicological medical emergency in India, where the majority of the population lives on...
Assessment of the Peradeniya Organophosphorus Poisoning Scale as a Severity and Prognostic Marker in Patients With Acute Organophosphorus Poisoning Presenting to an Emergency Medicine Department.
Background Organophosphorus (OP) compound poisoning is the most common toxicological medical emergency in India, where the majority of the population lives on agriculture. The Peradeniya Organophosphorus Poisoning (POP) scale can be a simple and effective system to determine the need for ventilatory support early in the course of admission. The objective of this study was to evaluate the prognostic value of the clinical parameters of the POP scale in predicting the severity of organophosphorus compound poisoning, by comparing early predicted patient prognosis evaluated by the POP scale on admission with the patient outcome. Methods This was a prospective observational study of acute organophosphorus compound poisoning presenting to the emergency department of Sir Sayajirao General (SSG) Hospital and Medical College, Baroda. We included patients over 12 years of age with a history of, or symptoms suggestive of, acute OP poisoning. The patients received initial resuscitation according to airway, breathing, circulation, disability, and exposure simultaneously with decontamination and gastric lavage by Ryle's tube. They also received the standard antidotes of atropine and pralidoxime immediately. We applied the POP scale to each patient upon admission and graded the poisoning severity as mild (a POP scale score of 0-3), moderate (4-7), or severe (8-11). This scale assessed the patients' need for mechanical ventilation and ICU management and their final clinical outcome. Results We enrolled 60 patients in the study. Most of them were under 20 years of age, and 65% of them were male. Social laborers were the major population, and most of them had suicidal intention. Monocrotophos was the most commonly consumed OP compound. Most of the patients were brought to the hospital within two to six hours of consumption. Vomiting and profuse secretions were the primary presenting symptoms. A majority of the patients (47) fell into the mild POP scale range. None of the patients had severe poisoning. Out of 60 patients, 49 patients improved and 11 patients died. Seven patients (15%) with mild POP scale scores and four patients (31%) with moderate scores died. Overall, 61.7% of patients with mild POP scale scores and 100% of patients with moderate scores needed mechanical ventilation. Conclusion The POP scale is an effective tool to measure severity and make a prognosis in patients with acute OP compound exposure. It may be a simple, inexpensive tool that may help predict the need for ventilatory support at admission. Early identification of danger signs may help in the reduction of mortality and morbidity when resources are limited. However, we found incorporating other clinical parameters and biochemical markers provides better prognostication than using the POP scale alone.
PubMed: 37448435
DOI: 10.7759/cureus.40277 -
Toxicology International Jan 2011An experimental study was conducted to evaluate the hepatotoxic effects in the progeny of dams treated with methimazole, monocrotophos (MCP) and lead acetate. Female...
An experimental study was conducted to evaluate the hepatotoxic effects in the progeny of dams treated with methimazole, monocrotophos (MCP) and lead acetate. Female pregnant albino rats of Wistar kyoto strain were divided into five groups and treated as follows, from day 3 of pregnancy till weaning of pups on postnatal day (PND) 21. Group 1 served as sham control, group 2 received methimazole 0.02% in drinking water, group 3 received MCP (0.3 mg/kg orally), group 4 received lead acetate at 0.2% in drinking water and group 5 received MCP + lead acetate. Thyroid hormone profile was recorded on 14 (th)day of gestation in dams. Eight pups from each group were euthanized on PND 21 and 90, and liver tissues were collected for analysis. Thiobarbituric acid reactive substances (TBARS), protein carbonyls and reduced glutathione (GSH) of liver were studied on PND 21 and 90, while the activities of Na (+)/K(+)ATPase and Mg (2+)ATPase in the liver were studied on PND 90. T(3), T(4), GSH, Na(+)/K(+)ATPase and Mg(2+)ATPase were significantly (P<0.05) decreased, while TBARS and protein carbonyls were significantly (P < 0.05) increased in all the test groups as compared to group 1. From this study, it is concluded that both MCP and lead acetate have a possible influence on thyroid gland of dams as the thyroid profile was altered significantly and the hepatotoxic effects were comparable to those induced by methimazole.
PubMed: 21430926
DOI: 10.4103/0971-6580.75868