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Biomolecules May 2024Olesoxime, a cholesterol derivative with an oxime group, possesses the ability to cross the blood-brain barrier, and has demonstrated excellent safety and tolerability...
Olesoxime, a cholesterol derivative with an oxime group, possesses the ability to cross the blood-brain barrier, and has demonstrated excellent safety and tolerability properties in clinical research. These characteristics indicate it may serve as a centrally active ligand of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), whose disruption of activity with organophosphate compounds (OP) leads to uncontrolled excitation and potentially life-threatening symptoms. To evaluate olesoxime as a binding ligand and reactivator of human AChE and BChE, we conducted kinetic studies with the active metabolite of insecticide parathion, paraoxon, and the warfare nerve agents sarin, cyclosarin, tabun, and VX. Our results showed that both enzymes possessed a binding affinity for olesoxime in the mid-micromolar range, higher than the antidotes in use (i.e., 2-PAM, HI-6, etc.). While olesoxime showed a weak ability to reactivate AChE, cyclosarin-inhibited BChE was reactivated with an overall reactivation rate constant comparable to that of standard oxime HI-6. Moreover, in combination with the oxime 2-PAM, the reactivation maximum increased by 10-30% for cyclosarin- and sarin-inhibited BChE. Molecular modeling revealed productive interactions between olesoxime and BChE, highlighting olesoxime as a potentially BChE-targeted therapy. Moreover, it might be added to OP poisoning treatment to increase the efficacy of BChE reactivation, and its cholesterol scaffold could provide a basis for the development of novel oxime antidotes.
Topics: Humans; Butyrylcholinesterase; Acetylcholinesterase; Ligands; Oximes; Cholinesterase Reactivators; Cholinesterase Inhibitors; Cholestenones; Kinetics; Sarin; GPI-Linked Proteins; Antidotes; Cholesterol; Organophosphorus Compounds
PubMed: 38785995
DOI: 10.3390/biom14050588 -
International Journal of Analytical... 2023Antibiotics and pesticides are widespread in most rivers and lakes due to the overuse of antibiotics and pesticides, but there are few methods for simultaneous analysis...
Antibiotics and pesticides are widespread in most rivers and lakes due to the overuse of antibiotics and pesticides, but there are few methods for simultaneous analysis of antibiotics and pesticides in aquatic environments. To address this knowledge gap, a concise and sensitive analytical method is proposed in which three classes of human and veterinary drugs (sulfonamides, macrolides, and hormones) and two classes of pesticides (organophosphorus and neonicotinoids) are simultaneously extracted and determined in surface water. The solid-phase extraction column with Cleanert PEP-2 was preconditioned sequentially with 6 mL of methanol, ultrapure water, and citric acid buffer (pH 3.0) each for simultaneous extraction and further purification. The forty-seven target analytes were analysed by LC-MS/MS in positive and negative ion modes. The LC separation was performed using a Sigma-Aldrich C column with 0.1% formic acid in water and acetonitrile as a gradient eluting mobile phase in positive ion mode. The internal standard method was used to overcome the inevitable matrix effects in LC-MS/MS analysis. The matrix effects of most target analytes were in the range of 27-151%. The recoveries of forty analytes in the three concentrations (10, 50, and 100 ng L) of surface water spiked samples ranged from 41 to 127%. The method quantitative limits of the analytes were in the range of 0.40-5.49 ng L. Application of the method to analyze samples in the eight runoff outlets of the Pearl River Delta showed that some antibiotics and pesticides were detected, and the concentration of parathion was as high as 154 ng L. A powerful tool for quickly and efficiently screening for contaminants in surface water has been presented.
PubMed: 37877028
DOI: 10.1155/2023/6350669 -
Global Challenges (Hoboken, NJ) Sep 2022Glyphosate is a globally applied herbicide yet it has been relatively undetectable in-field samples outside of gold-standard techniques. Its presumed nontoxicity toward...
Glyphosate is a globally applied herbicide yet it has been relatively undetectable in-field samples outside of gold-standard techniques. Its presumed nontoxicity toward humans has been contested by the International Agency for Research on Cancer, while it has been detected in farmers' urine, surface waters and crop residues. Rapid, on-site detection of glyphosate is hindered by lack of field-deployable and easy-to-use sensors that circumvent sample transportation to limited laboratories that possess the equipment needed for detection. Herein, the flavoenzyme, glycine oxidase, immobilized on platinum-decorated laser-induced graphene (LIG) is used for selective detection of glyphosate as it is a substrate for GlyOx. The LIG platform provides a scaffold for enzyme attachment while maintaining the electronic and surface properties of graphene. The sensor exhibits a linear range of 10-260 m, detection limit of 3.03 m, and sensitivity of 0.991 nA m . The sensor shows minimal interference from the commonly used herbicides and insecticides: atrazine, 2,4-dichlorophenoxyacetic acid, dicamba, parathion-methyl, paraoxon-methyl, malathion, chlorpyrifos, thiamethoxam, clothianidin, and imidacloprid. Sensor function is further tested in complex river water and crop residue fluids, which validate this platform as a scalable, direct-write, and selective method of glyphosate detection for herbicide mapping and food analysis.
PubMed: 36176938
DOI: 10.1002/gch2.202200057 -
RSC Advances Jun 2022To achieve rapid and convenient on-site pretreatment and determination of parathion-methyl, a density-adjusted liquid-phase microextraction with smartphone digital image...
Density-adjusted liquid-phase microextraction with smartphone digital image colorimetry to determine parathion-methyl in water, fruit juice, vinegar, and fermented liquor.
To achieve rapid and convenient on-site pretreatment and determination of parathion-methyl, a density-adjusted liquid-phase microextraction with smartphone digital image colorimetry was established to detect parathion-methyl in food samples. In this study, the environmentally friendly biomass-derived solvent guaiacol was used as the extractant. Salt and water, as density regulators, realized the two movements (floating-sinking) of the extractant and full contact between the extractant and the sample solution to establish an environmentally friendly, fast, and efficient pretreatment method. Under strong alkaline conditions, parathion-methyl generated a yellow product; then, a smartphone was used to obtain the image of the yellow product for intensity analysis. Parathion-methyl has a good linear relationship in the range of 0.01-1 mg L, and the limits of detection and quantification are 0.003 and 0.01 mg L, respectively. This method has been successfully applied to the determination of parathion-methyl in spiked water, fruit juice, vinegar, and fermented liquor with a recovery of 91.6-106.5% and a relative standard deviation of 0.6-6.0%. The established density-adjusted liquid phase microextraction with smartphone digital image colorimetry is rapid, convenient, and environmentally friendly for the determination of parathion-methyl in food samples.
PubMed: 35800312
DOI: 10.1039/d2ra02760g -
International Journal of Environmental... Aug 2022Pesticide-related mental health issues in Thailand, an upper-middle-income country, are not well known. This study aimed to investigate the association between the...
Pesticide-related mental health issues in Thailand, an upper-middle-income country, are not well known. This study aimed to investigate the association between the history of occupational exposure to pesticides and the mental health of Thai farmers. A cross-sectional study was carried out in the areas around Chiang Mai, a large city in Northern Thailand, between June 2020 and January 2021. A total of 6974 farmers from six districts were interviewed to determine whether they regularly experienced symptoms related to mental health by the Self-Reporting Questionnaire (SRQ-20) as well as their lifetime history of agricultural pesticide exposure from 31 active ingredients and five functional categories: insecticides, herbicides, fungicides, rodenticides, and molluscicides. The cut-off of 6 was used to evaluate probable mental disorder. Most of the farmers under investigation were men (53.8%), with a mean age of 55.2 (11.7) years, and were involved mainly in the planting of rice, fruit, and vegetables. About 86.7% reported having used pesticides on their crops at some point in their lives-mostly glyphosate, paraquat, 2,4-D, methomyl, and carbofuran. All functional groups, as well as pesticide classes like organochlorines, organophosphates, and carbamates, were significantly associated with a higher risk of probable mental disorder based on exposure duration, frequency, personal protective equipment usage, and hygienic behavior. In a model with multiple pesticides, there was an association between mental disorder and exposure to endosulfan (AOR = 2.27, 95%CI = 1.26-4.08) and methyl parathion (AOR = 2.26, 95%CI = 1.26-4.06). Having previously reported pesticide poisoning symptoms was related to mental disorder (AOR = 7.97, 95%CI = 5.16-12.31), the findings provided evidence of pesticide exposure posing a risk to farmers' mental health, particularly long-term and high-intensity exposure.
Topics: Agriculture; Cross-Sectional Studies; Farmers; Female; Health Status; Humans; Male; Middle Aged; Occupational Exposure; Pesticides; Thailand
PubMed: 35955007
DOI: 10.3390/ijerph19159654 -
Journal of Health & Pollution Dec 2020Cowpea is a leguminous crop commonly grown and eaten in Nigeria. Organophosphate insecticides are frequently used to control insect populations in cowpea crops.
BACKGROUND
Cowpea is a leguminous crop commonly grown and eaten in Nigeria. Organophosphate insecticides are frequently used to control insect populations in cowpea crops.
OBJECTIVES
The present study was conducted to investigate the concentrations of organophosphate insecticide residues in cowpea varieties in Gwagwalada, Nigeria, and assess health risks to consumers.
METHODS
Samples of brown and white cowpea varieties were collected from Gwagwalada market, Abuja, Nigeria. Concentrations of organophosphate insecticide residues in the cowpea samples were analyzed by gas chromatography-mass spectrometry with selective ion monitoring. Risk evaluation was carried out by the determination of estimated daily intake, hazard quotient and chronic hazard index.
RESULTS
The organophosphates detected in the cowpea varieties were malathion, parathion, ethion and carbophenothion. The concentrations of insecticides in the cowpea types were higher than the maximum residue limits recommended by the European Union (EU) and the Agency for Toxic Substances and Disease Registry (ATSDR). The hazard quotient values were less than 100% for malathion, parathion and ethion in the cowpea varieties for adults and children. The hazard quotient of carbophenothion for adults was below 100% for the cowpea types, while the hazard quotient surpassed 100% for children. The chronic hazard indexes for children were 364% and 276% for the brown and white cowpea types, respectively.
CONCLUSIONS
The results obtained in the present study indicate that consumers, particularly children, may be exposed to health risks through the consumption of cowpea types. Consequently, monitoring and regulation of organophosphate insecticide usage in Nigeria should be intensified.
PubMed: 33324500
DOI: 10.5696/2156-9614-10.28.201203 -
Ecotoxicology and Environmental Safety Oct 2022Urinary para-nitrophenol (PNP), an exposure biomarker of ethyl parathion (EP) and methyl parathion (MP) pesticides, was still pervasively detected in the general...
BACKGROUND
Urinary para-nitrophenol (PNP), an exposure biomarker of ethyl parathion (EP) and methyl parathion (MP) pesticides, was still pervasively detected in the general population even after global restriction for years. And the concern whether there is an association of PNP level with child development of the nervous system is increasing. The current study aimed to evaluate the maternal urinary PNP concentrations during late pregnancy and the associations of PNP levels with cognitive and motor function of their children at the age of 2 years.
METHODS
323 mother-child pairs from the Sheyang Mini Birth Cohort Study were included in the current study. Gas chromatography-tandem mass spectrometry was used to measure concentrations of PNP, the specific metabolite of EP and MP, in maternal urine samples during pregnancy. Developmental quotients (DQs) scores measured with Gesell Developmental Scales were employed to evaluate cognitive and motor function of children aged 2 years. Generalized linear models were performed to analyze the associations of PNP concentrations in pregnant women's urine samples with cognitive and motor function of their children.
RESULTS
Maternal PNP was detected in all urine samples with a median of 4.11 μg/L and a range from 0.57 μg/L to 109.13 μg/L, respectively. Maternal urinary PNP concentrations showed a negative trend with DQ of motor area [regression coefficient (β) = - 1.35; 95 % confidence interval (95 %CI): - 2.37, - 0.33; P < 0.01], and the children whose mothers were in the fourth quartile exposure group performed significantly worse compared to the reference group (β = - 1.11; 95 %CI: - 1.80, - 0.42; P < 0.01). As for average DQ score, children with their mothers' urinary PNP concentrations in the third quartile group had higher scores than those in the first quartile group (β = 0.39; 95 %CI: 0.03, 0.75; P = 0.04). In sex-stratified analyses, a negative trend between maternal urinary PNP concentrations and DQ scores in motor area of children was only observed in boys (β = - 1.62; 95 %CI: - 2.80, - 0.43; P < 0.01). Boys in the third quartile group had higher DQ average scores than those in the lowest quartile as reference (β = 0.53; 95 %CI: 0.02, 1.04; P = 0.04).
CONCLUSIONS
The mothers from SMBCS may be widely exposed to EP and/or MP, which were associated with the cognitive and motor function of their children aged 2 years in a sex-specific manner. Our results might provide epidemiology evidence on the potential effects of prenatal exposure to EP and/or MP on children's cognitive and motor function.
Topics: Biomarkers; China; Cognition; Cohort Studies; Female; Gas Chromatography-Mass Spectrometry; Humans; Male; Methyl Parathion; Nitrophenols; Pesticides; Pregnancy; Pregnant Women
PubMed: 36075123
DOI: 10.1016/j.ecoenv.2022.114051 -
ACS Omega Feb 2022Graphene-enhanced Raman scattering (GERS) produces enhancement of the Raman signal, which is based on chemical rather than electromagnetic mechanism such as in the...
Graphene-enhanced Raman scattering (GERS) produces enhancement of the Raman signal, which is based on chemical rather than electromagnetic mechanism such as in the surface-enhanced Raman scattering. Graphene oxide, amino- and guanidine-functionalized graphene oxide, exfoliated graphene, and commercial graphene nanoplatelets have been used to investigate the GERS response with the change of graphene properties. Different graphene nanostructures have been embedded into organic-inorganic microporous films to build a platform for the fast and sensitive detection of pesticides in water. The graphene nanostructures vary in the number of layers, lateral size, degree of oxidation, and surface functionalization. The GERS performances of the graphene nanostructures cast on silicon substrates and embedded in the nanocomposite films have been comparatively evaluated. After casting a few droplets of the pesticide aqueous solution on the graphene nanostructures, the Raman band enhancements of the analytes have been measured. In the nanocomposite films, the characteristic Raman bands originating from pesticides such as paraoxon, parathion, and glyphosate could be traced at concentrations below 10, 10, and 10 M, respectively. The results show that the surface functionalization reduces the GERS effect because it increases the ratio between the sp carbon and sp carbon. On the other hand, the comparison among different types of graphenes shows that the monolayers are more efficient than the few-layer nanostructures in enhancing the Raman signal.
PubMed: 35224328
DOI: 10.1021/acsomega.1c04863 -
Oncology Reports Apr 2021Cancer development is a multistep process that may be induced by a variety of compounds. Environmental substances, such as pesticides, have been associated with...
Cancer development is a multistep process that may be induced by a variety of compounds. Environmental substances, such as pesticides, have been associated with different human diseases. Organophosphorus pesticides (OPs) are among the most commonly used insecticides. Despite the fact that organophosphorus has been associated with an increased risk of cancer, particularly hormone‑mediated cancer, few prospective studies have examined the use of individual insecticides. Reported results have demonstrated that OPs and estrogen induce a cascade of events indicative of the transformation of human breast epithelial cells. studies analyzing an immortalized non‑tumorigenic human breast epithelial cell line may provide us with an approach to analyzing cell transformation under the effects of OPs in the presence of estrogen. The results suggested hormone‑mediated effects of these insecticides on the risk of cancer among women. It can be concluded that, through experimental models, the initiation of cancer can be studied by analyzing the steps that transform normal breast cells to malignant ones through certain substances, such as pesticides and estrogen. Such substances cause genomic instability, and therefore tumor formation in the animal, and signs of carcinogenesis . Cancer initiation has been associated with an increase in genomic instability, indicated by the inactivation of tumor‑suppressor genes and activation of oncogenes in the presence of malathion, parathion, and estrogen. In the present study, a comprehensive summary of the impact of OPs in human and rat breast cancer, specifically their effects on the cell cycle, signaling pathways linked to epidermal growth factor, drug metabolism, and genomic instability in an MCF‑10F estrogen receptor‑negative breast cell line is provided.
Topics: Animals; Breast; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Cell Transformation, Neoplastic; Epithelial Cells; Estrogens; Female; Genomic Instability; Humans; Insecticides; Malathion; Parathion; Rats; Signal Transduction
PubMed: 33649804
DOI: 10.3892/or.2021.7975 -
American Journal of Respiratory Cell... Nov 2019Epidemiologic studies link organophosphorus pesticides (OPs) to increased incidence of asthma. In guinea pigs, OP-induced airway hyperreactivity requires macrophages and...
Epidemiologic studies link organophosphorus pesticides (OPs) to increased incidence of asthma. In guinea pigs, OP-induced airway hyperreactivity requires macrophages and TNF-α. Here, we determined whether OPs interact directly with macrophages to alter cytokine expression or release. Human THP1 cells were differentiated into macrophages and then exposed to parathion, chlorpyrifos, or diazinon, or their oxon, phosphate, or phosphorothioate metabolites for 24 hours in the absence or presence of reagents that block cholinergic receptors. , , platelet-derived growth factor, and transforming growth factor-β mRNA and protein were quantified by qPCR and ELISA, respectively. The effects of OPs on NF-κB, acetylcholinesterase, and intracellular calcium were also measured. Parent OPs and their oxon metabolites upregulated cytokine mRNA and stimulated cytokine release. TNF-α release, which was the most robust response, was triggered by parent, but not oxon, compounds. Cytokine expression was also increased by diethyl dithiophosphate but not diethyl thiophosphate or diethyl phosphate metabolites. Parent OPs, but not oxon metabolites, activated NF-κB. Parent and oxon metabolites decreased acetylcholinesterase activity, but comparable acetylcholinesterase inhibition by eserine did not mimic OP effects on cytokines. Consistent with the noncholinergic mechanisms of OP effects on macrophages, pharmacologic antagonism of muscarinic or nicotinic receptors did not prevent OP-induced cytokine expression or release. These data indicate that phosphorothioate OP compounds directly stimulate macrophages to release TNF-α, potentially via activation of NF-κB, and suggest that therapies that target NF-κB may prevent OP-induced airway hyperreactivity.
Topics: Asthma; Bronchial Hyperreactivity; Bronchoconstriction; Cell Differentiation; Chlorpyrifos; Cytokines; Diazinon; Humans; Insecticides; Organophosphorus Compounds; Parathion
PubMed: 30978295
DOI: 10.1165/rcmb.2018-0257OC