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Scientific Reports Mar 2016Robust and sensitive detection systems are a crucial asset for risk management of chemicals, which are produced in increasing number and diversity. To establish an in...
Robust and sensitive detection systems are a crucial asset for risk management of chemicals, which are produced in increasing number and diversity. To establish an in vivo biosensor system with quantitative readout for potential toxicant effects on motor function, we generated a transgenic zebrafish line TgBAC(hspb11:GFP) which expresses a GFP reporter under the control of regulatory elements of the small heat shock protein hspb11. Spatiotemporal hspb11 transgene expression in the musculature and the notochord matched closely that of endogenous hspb11 expression. Exposure to substances that interfere with motor function induced a dose-dependent increase of GFP intensity beginning at sub-micromolar concentrations, while washout of the chemicals reduced the level of hspb11 transgene expression. Simultaneously, these toxicants induced muscle hyperactivity with increased calcium spike height and frequency. The hspb11 transgene up-regulation induced by either chemicals or heat shock was eliminated after co-application of the anaesthetic MS-222. TgBAC(hspb11:GFP) zebrafish embryos provide a quantitative measure of muscle hyperactivity and represent a robust whole organism system for detecting chemicals that affect motor function.
Topics: Animals; Animals, Genetically Modified; Azinphosmethyl; Biosensing Techniques; Dose-Response Relationship, Drug; Founder Effect; Galantamine; Gene Expression Regulation; Green Fluorescent Proteins; Intracellular Signaling Peptides and Proteins; Motor Activity; Muscles; Mutant Chimeric Proteins; Notochord; Pesticides; Promoter Regions, Genetic; Propoxur; Zebrafish
PubMed: 27029555
DOI: 10.1038/srep23768 -
Frontiers in Neuroscience 2019Poisoning with organophosphorus compounds (OPCs) is a major problem worldwide. Standard therapy with atropine and established oxime-type enzyme reactivators... (Review)
Review
Poisoning with organophosphorus compounds (OPCs) is a major problem worldwide. Standard therapy with atropine and established oxime-type enzyme reactivators (pralidoxime, obidoxime) is unsatisfactory. In search of more efficacious broad-spectrum oximes, new bispyridinium (K-) oximes have been synthesized, with K027 being among the most promising. This review summarizes pharmacokinetic characteristics of K027, its toxicity and efficacy to protect from OPC toxicity and compares this oxime with another experimental bisquaternary asymmetric pyridinium aldoxime (K048) and two established oximes (pralidoxime, obidoxime). After intramuscular (i.m.) injection, K027 reaches maximum plasma concentration within ∼30 min; only ∼2% enter the brain. Its intrinsic cholinesterase inhibitory activity is low, making it relatively non-toxic. reactivation potency is high for ethyl-paraoxon-, methyl-paraoxon-, dichlorvos-, diisopropylfluorophosphate (DFP)- and tabun-inhibited cholinesterase. When administered after exposure to the same OPCs, K027 is comparable or more efficacious than pralidoxime and obidoxime. When given as a pretreatment before exposure to ethyl-paraoxon, methyl-paraoxon, DFP, or azinphos-methyl, it is superior to the Food and Drug Administration-approved compound pyridostigmine and comparable to physostigmine, which because of its entry into the brain may cause unwanted behavioral effects. Because of its low toxicity, K027 can be given in high dosages, making it a very efficacious oxime not only for postexposure treatment but also for prophylactic administration, especially when brain penetration is undesirable.
PubMed: 31191210
DOI: 10.3389/fnins.2019.00427 -
Journal of Occupational and... Dec 2018Organophosphorus pesticides (OPs) are commonly applied to agricultural crops. Families living in these communities may have higher exposure to OPs due to take home...
Organophosphorus pesticides (OPs) are commonly applied to agricultural crops. Families living in these communities may have higher exposure to OPs due to take home exposures and close proximity to agricultural fields. The objectives of this study were to measure OP concentrations in home carpet dust in agricultural and non-agricultural households and examine factors that may impact OP concentrations such as occupation, housing characteristics, and resident behaviors. Agricultural households had at least one parent who worked in agriculture during the previous 5 years. Carpet dust samples were collected at two time points from 278 households in an agricultural community located in the Pacific Northwest from 2008-2011. Samples were analyzed for four types of OPs: azinphos-methyl, phosmet, malathion, and chlorpyrifos. Overall, OP detection frequencies and concentrations were higher in agricultural households compared to non-agricultural households. Factors associated with higher OP concentrations in home carpet dust were identified and included: (1) homes with two or more agricultural workers living in the home, (2) homes located in close proximity to an agricultural field or orchard, (3) having an entry floor mat, and (4) frequently vacuuming the house. Having air conditioning in the home had a protective effect with OP concentrations. While the use of these four OPs is restricted or limited for residential use in the United States, results show that they were still found in the indoor environment. The understanding of the impact of agricultural work and other factors that elevate levels of OPs in the home is crucial to mitigating pesticide exposure in agricultural communities.
Topics: Adult; Child; Child, Preschool; Dust; Environmental Exposure; Farmers; Farms; Floors and Floorcoverings; Housing; Humans; Northwestern United States; Occupational Exposure; Organothiophosphates; Parents; Pesticide Residues
PubMed: 30138040
DOI: 10.1080/15459624.2018.1515489 -
Insects Dec 2021The codling moth, L. (Lepidoptera, Tortricidae), is a serious invasive pest of pome fruits. Currently, management mainly relies on the application of insecticides,...
The codling moth, L. (Lepidoptera, Tortricidae), is a serious invasive pest of pome fruits. Currently, management mainly relies on the application of insecticides, which have driven the development of resistance in the insect. Understanding the genetic mechanisms of insecticide resistance is of great significance for developing new pest resistance management techniques and formulating effective resistance management strategies. Using existing genome resequencing data, we performed selective sweep analysis by comparing two resistant strains and one susceptible strain of the insect pest and identified seven genes, among which, two (glycine receptor and glutamate receptor) were under strong insecticide selection, suggesting their functional importance in insecticide resistance. We also found that eight genes including , , , , and , are potentially involved in cross-resistance to azinphos-methyl and deltamethrin. Moreover, among several P450s identified as positively selected genes, , , and showed the highest expression level in larva compared to other stages tested, and also showed the highest expression level in midgut, supporting the roles they may play in insecticide metabolism. Our results provide several potential genes that can be studied further to advance understanding of complexity of insecticide resistance mechanisms in .
PubMed: 35055845
DOI: 10.3390/insects13010002 -
Analytical Biochemistry May 2021Intentional or unintentional intake of anticholinesterase pesticides became common due to their extensive use in agricultural and domestic purposes, resulting in...
Intentional or unintentional intake of anticholinesterase pesticides became common due to their extensive use in agricultural and domestic purposes, resulting in numerous poisoning cases. A simple, accurate, and sensitive gas chromatography-ion trap mass spectrometry-based method for the quantification of 12 anticholinesterase pesticides (monocrotophos, dimethoate, dichlorvos, azinphos-methyl, carbofuran, chlorpyrifos, dialifos, diazinon, malathion, parathion, methidathion, and terbufos) in serum was developed, and its utility in patients with alleged pesticides poisoning was assessed. The quantification was performed using liquid-liquid extraction by toluene/chloroform (4:1,v/v) with 500 μL of serum. On column limit of detection and limit of quantification were less than 50.00 μg/L. The recovery ranged from 97.54 to 103.23%. The calibration curves were linear (R > 0.9937). Accuracy was found to be between - 7.1 and 7.2%. Intra-day and inter-day reproducibility was less than 17% for the spiked quality control serum samples. The level of pesticide in serum quantified by the validated method correlated with clinical signs and symptoms, pseudo-cholinesterase activity, total atropine dose, length of hospital stay, and clinical outcome in 15 patients with alleged pesticide poisoning. The validated method may be used for monitoring and prognosis in patients with pesticide poisoning and diagnosis of poisoning in forensic toxicology.
Topics: Calibration; Cholinesterase Inhibitors; Gas Chromatography-Mass Spectrometry; Humans; Liquid-Liquid Extraction; Pesticides; Reproducibility of Results; Spectrometry, Mass, Electrospray Ionization
PubMed: 33705722
DOI: 10.1016/j.ab.2021.114158 -
Aquatic Toxicology (Amsterdam,... Nov 2016Organophosphate insecticides (OPs) continue to be an important class of agrochemicals used in modern agriculture worldwide. Even though these pesticides persist in the...
In vitro and in vivo studies of cholinesterases and carboxylesterases in Planorbarius corneus exposed to a phosphorodithioate insecticide: Finding the most sensitive combination of enzymes, substrates, tissues and recovery capacity.
Organophosphate insecticides (OPs) continue to be an important class of agrochemicals used in modern agriculture worldwide. Even though these pesticides persist in the environment for a relatively short time, they show a high acute toxicity that may represent a serious hazard for wildlife. Sub-lethal effects on non-target species are a focus in pest management programs and should be used as biomarkers. Cholinesterases (ChEs) are the most used biomarker of OP exposure in vertebrate and invertebrate species. However, the combined monitoring of ChE and carboxylesterase (CE) activities may provide a more useful indication of exposure and effect of the organisms. The objective of the present work was to find the most sensitive combination of enzyme, substrate, tissue and capacity to recovery of B-esterases in the freshwater gastropod Planorbarius corneus exposed to the OP azinphos-methyl. For this purpose, ChE and CE activities in different tissues of P. corneus (head-foot, pulmonary region, digestive gland, gonads and whole organism soft tissue) were studied. Measurements of ChE activity were performed using three substrates: acetylthiocholine, propionylthiocholine and butyrylthiocholine and CE activity using four different substrates: p-nitrophenyl acetate, p-nitrophenyl butyrate, 1-naphthyl acetate, and 2-naphthyl acetate in control and exposed organisms. Finally, the recovery rates of ChE and CE activities following 48h exposure to azinphos-methyl were analyzed. Our results show a preference for acetylthiocholine as substrate, a high inhibition with eserine (a selective ChE inhibitor) and inhibition with excess of substrate in all the analyzed tissues. The highest ChE and CE activity was found in the pulmonary region and in the digestive gland, respectively. The highest CE V was obtained with 1 and 2-naphthyl acetate in all the tissues. CEs were more sensitive than ChE to azinphos-methyl exposure. The highest sensitivity was found using p-nitrophenyl acetate and butyrate as substrates. On the other hand, CEs of the digestive gland and the pulmonary region were more sensitive than CEs of the whole organism soft tissue. Regarding the recovery of enzyme activities after 48h exposure, ChE and CEs with p-nitrophenyl butyrate reached control values after 14days in the digestive gland and after 21days in the pulmonary region. Our results show marked differences in P. corneus basal ChE and CE activities depending on substrates and the tissue. Also, both tissue-dependent and substrate-dependent variations in sensitivity to azinphos-methyl exposure and recovery were obtained. CEs measured with p-nitrophenyl butyrate in the pulmonary region were the best combination to be used as biomarker of exposure to azinphos-methyl due to their sensitivity and low recovery capacity. Environmental concentrations of azinphos-methyl inhibited CE activity so they could be used as effective biomarkers of aquatic contamination.
Topics: Animals; Azinphosmethyl; Biomarkers; Butyrates; Carboxylic Ester Hydrolases; Cholinesterases; Inhibitory Concentration 50; Insecticides; Kinetics; Nitrophenols; Organophosphorus Compounds; Snails; Substrate Specificity; Water Pollutants, Chemical
PubMed: 27723570
DOI: 10.1016/j.aquatox.2016.10.002 -
Aquatic Toxicology (Amsterdam,... Aug 2016Biochemical effects of azinphosmethyl (AZM), an organophosphate pesticide, were determined in gill, brain and muscle tissues of Odontesthes hatcheri and Jenynsia... (Comparative Study)
Comparative Study
Biochemical effects of azinphosmethyl (AZM), an organophosphate pesticide, were determined in gill, brain and muscle tissues of Odontesthes hatcheri and Jenynsia multidentata. The 96-h toxicity was first assessed, estimating lethal concentrations fifty (LC50) of 7 and 30μgL(-1) AZM for O. hatcheri and J. multidentata, respectively. Considering the LC50, sublethal 96-h static exposures were designed for O. hatcheri (0.1-0.5μgL(-1) AZM) and J. multidentata (5-10μgL(-1)AZM) to determine biochemical endpoints. Brain acetylcholinesterase (AchE) was inhibited by AZM in both species, while the buffer enzyme carboxylesterase (CarbE) was not affected in this tissue. Conversely, muscular AchE was not affected but CarbE was augmented by AZM. The enzymes glutathione reductase, glutathione-S-transferase and CarbE were significantly inhibited in O. hatcheri gills but none of them was affected by AZM in J. multidentata gills compared to control. GSH levels were augmented in gills of both species in exposed fish compared to controls and in addition, lipid peroxidation was significantly increased in O. hatcheri gills. Ex vivo histochemical analysis of ROS by fluorescence microscopy was also performed in J. multidentata gills, indicating a significant increase upon exposure to 10μgL(-1) AZM. Principal component analyses (PCA) were applied, both to the species together or separately. The general analysis demonstrated a clear separation of responses in the two species. For O. hatcheri, the variable that explains the major variation in PC1 is gill catalase and brain AchE in PC2. In J. multidentata in turn, the variable that explains the major variation in PC1 is brain AchE and total oxyradical scavenging capacity in PC2. The toxicity data and biomarker responses obtained for both species were compared to environmental concentrations of AZM detected in superficial water from different points in the Alto Valle region and risk quotients (RQ) were calculated. This approach indicated probable acute effects for O. hatcheri in river and irrigation channels (RQ>0.1), while the risk was unacceptable in drainage superficial water (RQ>1). In contrast, J. multidentata showed minimal risk in river or channel water (RQ<0.1) and probable risk in drainage water (RQ=0.75). We conclude that not only the differential susceptibility of both species to AZM is environmentally relevant, but also that the different biomarkers responding in each case underlie particular pathways stressed by this agrochemical.
Topics: Animals; Argentina; Azinphosmethyl; Biomarkers; Body Burden; Brain; Female; Fishes; Gills; Insecticides; Lipid Peroxidation; Oxidative Stress; Principal Component Analysis; Toxicity Tests; Water Pollutants, Chemical
PubMed: 27376960
DOI: 10.1016/j.aquatox.2016.06.015 -
Pesticide Biochemistry and Physiology Feb 2016Detoxification by glutathione S-transferases (GSTs) and esterases are important mechanisms associated with insecticide resistance. Discovery of novel GST and esterase...
Detoxification by glutathione S-transferases (GSTs) and esterases are important mechanisms associated with insecticide resistance. Discovery of novel GST and esterase inhibitors from phytochemicals could provide potential new insecticide synergists. Conifer tree species contain flavonoids, such as taxifolin, that inhibit in vitro GST activity. The objectives were to test the relative effectiveness of taxifolin as an enzyme inhibitor and as an insecticide synergist in combination with the organophosphorous insecticide, Guthion (50% azinphos-methyl), and the botanical insecticide, pyrethrum, using an insecticide-resistant Colorado potato beetle (CPB) Leptinotarsa decemlineata (Say) strain. Both taxifolin and its isomer, quercetin, increased the mortality of 1(st) instar CPB larvae after 48h when combined with Guthion, but not pyrethrum. Taxifolin had greater in vitro esterase inhibition compared with the commonly used esterase inhibitor, S, S, S-tributyl phosphorotrithioate (DEF). An in vivo esterase and GST inhibition effect after ingestion of taxifolin was measured, however DEF caused a greater suppression of esterase activity. This study demonstrated that flavonoid compounds have both in vitro and in vivo esterase inhibition, which is likely responsible for the insecticide synergism observed in insecticide-resistant CPB.
Topics: Animals; Coleoptera; Esterases; Flavonoids; Glutathione Transferase; Insecticides; Tracheophyta
PubMed: 26821651
DOI: 10.1016/j.pestbp.2015.09.003 -
International Journal of Molecular... Mar 2021Poisoning with organophosphorus compounds (OPCs) represents an ongoing threat to civilians and rescue personal. We have previously shown that oximes, when administered...
Poisoning with organophosphorus compounds (OPCs) represents an ongoing threat to civilians and rescue personal. We have previously shown that oximes, when administered prophylactically before exposure to the OPC paraoxon, are able to protect from its toxic effects. In the present study, we have assessed to what degree experimental (K-27; K-48; K-53; K-74; K-75) or established oximes (pralidoxime, obidoxime), when given as pretreatment at an equitoxic dosage of 25% of LD, are able to reduce mortality induced by the OPC azinphos-methyl. Their efficacy was compared with that of pyridostigmine, the only FDA-approved substance for such prophylaxis. Efficacy was quantified in rats by Cox analysis, calculating the relative risk of death (RR), with RR=1 for the reference group given only azinphos-methyl, but no prophylaxis. All tested compounds significantly ( ≤ 0.05) reduced azinphos-methyl-induced mortality. In addition, the efficacy of all tested experimental and established oximes except K-53 was significantly superior to the FDA-approved compound pyridostigmine. Best protection was observed for the oximes K-48 (RR = 0.20), K-27 (RR = 0.23), and obidoxime (RR = 0.21), which were significantly more efficacious than pralidoxime and pyridostigmine. The second-best group of prophylactic compounds consisted of K-74 (RR = 0.26), K-75 (RR = 0.35) and pralidoxime (RR = 0.37), which were significantly more efficacious than pyridostigmine. Pretreatment with K-53 (RR = 0.37) and pyridostigmine (RR = 0.52) was the least efficacious. Our present data, together with previous results on other OPCs, indicate that the experimental oximes K-27 and K-48 are very promising pretreatment compounds. When penetration into the brain is undesirable, obidoxime is the most efficacious prophylactic agent already approved for clinical use.
Topics: Animals; Azinphosmethyl; Cholinesterase Inhibitors; Inhibitory Concentration 50; Molecular Weight; Organophosphorus Compounds; Oximes; Pesticides; Proportional Hazards Models; Rats, Wistar; Risk; Survival Analysis; Rats
PubMed: 33802843
DOI: 10.3390/ijms22063072 -
Spectrochimica Acta. Part A, Molecular... Aug 2019Development of simple and rapid methods for identification of pesticides, due to their broad usage and harmful effects on mammals, has been known as a critical demand....
Development of simple and rapid methods for identification of pesticides, due to their broad usage and harmful effects on mammals, has been known as a critical demand. Herein, we have introduced a silver nanoparticle (AgNP) based colorimetric sensor array for simultaneous identification of Azinphosmethyl (AM) and Phosalone (PS) pesticides. In the presence of the target pesticides, unmodified AgNPs at various pHs (4.5, 5.5 and 9.5) showed different aggregation behaviors. As a result of aggregation, the color and UV-Vis spectra of AgNPs changed differentially, leading to distinct response patterns for AM and PS. The aggregation induced spectral changes of AgNPs, were used to identify AM and PS with the help of linear discriminant analysis (LDA). The applicability of the proposed sensor array was then evaluated by identifying the target pesticides in apple samples. Altogether, the developed AgNPs based colorimetric sensor array can be potentially exploited as an efficient discrimination tool in the near future for agrichemical applications.
Topics: Azinphosmethyl; Colorimetry; Food Contamination; Hydrogen-Ion Concentration; Malus; Metal Nanoparticles; Organothiophosphorus Compounds; Pesticides; Silver
PubMed: 31077953
DOI: 10.1016/j.saa.2019.04.074