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Brain Sciences Apr 2023Organophosphate (OP) and carbamate pesticides are toxic to pests through targeted inhibition of acetylcholinesterase (AChE). However, OPs and carbamates may be harmful...
Differentiated Neurons Are More Vulnerable to Organophosphate and Carbamate Neurotoxicity than Undifferentiated Neurons Due to the Induction of Redox Stress and Accumulate Oxidatively-Damaged Proteins.
Organophosphate (OP) and carbamate pesticides are toxic to pests through targeted inhibition of acetylcholinesterase (AChE). However, OPs and carbamates may be harmful to non-target species including humans and could induce developmental neurotoxicity if differentiated or differentiating neurons are particularly vulnerable to neurotoxicant exposures. Hence, this study compared the neurotoxicity of OPs, chlorpyrifos-oxon (CPO), and azamethiphos (AZO) and the carbamate pesticide, aldicarb, to undifferentiated versus differentiated SH-SY5Y neuroblastoma cells. OP and carbamate concentration-response curves for cell viability were undertaken using 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays and cellular bioenergetic capacity assessed via quantitation of cellular ATP levels. Concentration-response curves for inhibition of cellular AChE activity were also generated and the production of reactive oxygen species (ROS) was monitored using a 2',7'-dichlorofluorescein diacetate (DCFDA) assay. The OPs and aldicarb reduced cell viability, cellular ATP levels, and neurite outgrowth in a concentration-dependent fashion, from a threshold concentration of ≥10 µM. Neurotoxic potency was in the order AZO > CPO > aldicarb for undifferentiated cells but CPO > AZO > aldicarb for differentiated cells and this toxic potency of CPO reflected its more extensive induction of reactive oxygen species (ROS) and generation of carbonylated proteins that were characterized by western blotting. Hence, the relative neurotoxicity of the OPs and aldicarb in part reflects non-cholinergic mechanisms that are likely to contribute to developmental neurotoxicity.
PubMed: 37239200
DOI: 10.3390/brainsci13050728 -
Aquatic Toxicology (Amsterdam,... Jul 2023Pesticide contamination in water resources is a global threat. Although usually found at low concentrations, pesticides raise considerable toxicological concerns, mainly...
Pesticide contamination in water resources is a global threat. Although usually found at low concentrations, pesticides raise considerable toxicological concerns, mainly when mixtures are considered. The occurrence of 22 pesticides (2,4 D, alachlor, aldicarb, aldrin, atrazine, carbendazim, carbofuran, chlordane, chlorpyrifos, DDT, diuron, glyphosate, lindane, mancozeb, methamidophos, metolachlor, molinate, profenofos, simazine, tebuconazole, terbufos, and trifluralin) was investigated, through consolidated database information, in surface freshwaters of Brazil. Moreover, scenarios of environmental risk assessment considering isolated compounds and mixtures were performed, as well as a meta-analytic approach for toxicity purposes. Pesticides in freshwater have been reported from 719 cities (12.9% of Brazilian cities), where 179 (3.2%) showed pesticide occurrence above the limit of detection or quantification. Considering cities with more than five quantified, 16 cities were prone to environmental risks considering individual risks. However, the number increased to 117 cities when the pesticide mixture was considered. The mixture risk was driven by atrazine, chlorpyrifos, and DDT. The national maximum acceptable concentrations (MAC) for nearly all pesticides are higher than the predicted no-effect concentration (PNEC) for the species evaluated, except aldrin. Our results show the need to consider mixtures in the environmental risk assessment to avoid underestimation and review MAC to protect aquatic ecosystems. The results presented here may guide the revision of the national environmental legislation to ensure the protection of Brazilian aquatic ecosystems.
Topics: Pesticides; Brazil; Chlorpyrifos; Atrazine; Ecosystem; Aldrin; DDT; Water Pollutants, Chemical; Fresh Water; Risk Assessment; Environmental Monitoring
PubMed: 37196509
DOI: 10.1016/j.aquatox.2023.106566 -
(Protein Kinase D1) mutants have age-dependent defects in locomotion and neuromuscular transmission.MicroPublication Biology 2023Changes in neuronal function that occur with age are an area of increasing importance. A potential significant contributor to age-dependent decline may be alterations to...
Changes in neuronal function that occur with age are an area of increasing importance. A potential significant contributor to age-dependent decline may be alterations to neurotransmitter release. Protein kinases, such as Protein Kinase C and Protein Kinase A, are well characterised modulators of neuronal function and neurotransmission. Protein Kinase D (PRKD) is a serine/threonine kinase whose role in neurons is less well characterised. Here we report that mutations in the PRKD homolog, , show an acceleration in age-dependent decline of locomotion rate and an alteration to age-dependent changes in aldicarb sensitivity. These effects could be explained by a pre- or post-synaptic function of the protein kinase as the animal ages.
PubMed: 37090152
DOI: 10.17912/micropub.biology.000800 -
Plant Disease Sep 2023Increased populations of in southeastern Idaho are associated with increased planting of susceptible cereal cultivars and lack of crop rotation. Identifying high-yield,...
Increased populations of in southeastern Idaho are associated with increased planting of susceptible cereal cultivars and lack of crop rotation. Identifying high-yield, resistant spring wheat cultivars with tolerance requires testing new genotypes and susceptibility assessments of marketed cultivars. We conducted two experiments to determine whether cultivars with putative resistance could maintain acceptable yield in the presence of . We also evaluated the tolerance response in relation to previously tested cultivars. Seven spring wheat cultivars were planted in two irrigated commercial fields that were naturally infested with high populations of . Measures of resistance, tolerance, and grain yield were assessed in aldicarb-treated versus nontreated plots. In aldicarb-treated plots in both years, grain yield of the susceptible cultivars Snow Crest, WestBred 936, WB9411, Patwin-515, and WB9668 was significantly increased. The expected yield increase with aldicarb was limited for the moderately susceptible Expresso due to water stress. 'WB-Rockland', carrying the resistance gene, maintained its standard yield, while none of the other cultivars in the experiment showed resistance or tolerance. Our results indicated that aldicarb improves wheat grain yield in irrigated crop production systems, and although removed from the market, it is effective and has utility for research. The results also support the hypothesis that high yield susceptible cultivars can mask the effect of on grain yield when managed appropriately.
Topics: Animals; Triticum; Edible Grain; Aldicarb; Idaho; Tylenchoidea; Cysts
PubMed: 36774578
DOI: 10.1094/PDIS-08-22-1820-RE -
Pesticide Biochemistry and Physiology Nov 2022Grammicin (Gra) is derived from the endophytic fungus Xylaria grammica EL000614 and shows nematicidal activity against the devastating root-knot nematode Meloidogyne...
Grammicin (Gra) is derived from the endophytic fungus Xylaria grammica EL000614 and shows nematicidal activity against the devastating root-knot nematode Meloidogyne incognita in-vitro, in planta, and in-field experiments. However, the mechanism of the nematicidal action of Gra remains unclear. In this study, Gra exposure to the model genetic organism Caenorhabditis elegans affected its L1, L2/3, L4, and young adult stages. In addition, Gra treatment increased the intracellular reactive oxygen species (ROS) levels of C. elegans and M. incognita. Molecular docking interaction analysis indicated that Gra could bind and interact with GCS-1, GST-4, and DAF-16a in order of low binding energy, followed by SOD-3, SKN-1, and DAF-16b. This implies that the anthelmintic action of Gra is related to the oxidative stress response. To validate this mechanism, we examined the expression of the genes involved in the oxidative stress responses following treatment with Gra using transgenic C. elegans strains such as the TJ356 strain zIs356 [daf-16p::daf-16a/b::GFP + rol-6 (su1006)], LD1 ldIs7 [skn-1p::skn-1b/c::GFP + rol-6 (su1006)], LD1171 ldIs3 [gcs-1p::GFP + rol-6 (su1006)], CL2166 dvIs19 [(pAF15) gst-4p::GFP::NLS], and CF1553 strain muIs84 [(pAD76) sod-3p::GFP + rol-6 (su1006)]. Gra treatment caused nuclear translocation of DAF-16/FoxO and enhanced gst-4::GFP expression, but it had no change in sod-3::GFP expression. These results indicate that Gra induces oxidative stress response via phase II detoxification without reduced cellular redox machinery. Gra treatment also inhibited the nuclear localization of SKN-1::GFP in the intestine, which may lead to a condition in which oxidative stress tolerance is insufficient to protect C. elegans by the inactivation of SKN-1, thus inducing nematode lethality. Furthermore, Gra caused the mortality of two mutant strains of C. elegans, CB113 and DA1316, which are resistant to aldicarb and ivermectin, respectively. This indicates that the mode of action of Gra is different from the traditional nematicides currently in use, suggesting that it could help develop novel approaches to control plant-parasitic nematodes.
Topics: Animals; Caenorhabditis elegans; Molecular Docking Simulation; Antinematodal Agents; Aldicarb; Tylenchida; Superoxide Dismutase
PubMed: 36464355
DOI: 10.1016/j.pestbp.2022.105244 -
Journal of Forensic and Legal Medicine Nov 2022Pesticides play a pivotal role in modern agricultural practices and effective domestic pest control. Despite their advantages, pesticides pose a great danger to humans... (Review)
Review
Pesticides play a pivotal role in modern agricultural practices and effective domestic pest control. Despite their advantages, pesticides pose a great danger to humans and animals due to their toxicity. Pesticides, particularly carbamates, are extensively used all over the world in crop protection and domestic pest control, however, also causing morbidity and mortality on a larger scale, which is of great significance in both clinical and criminal justice management.Carbamates are derived from a carbamic acid (NHCOOH) that are commonly used as insecticides. Ethienocarb, Sevin, Carbaryl, Fenoxycarb, Furadan, Carbofuran, Aldicarb, and 2-(1-Methylpropyl) phenyl N-methylcarbamate are examples of insecticides that include the carbamate functional group. By reversibly inactivating the enzyme acetylcholinesterase, these insecticides can induce cholinesterase inhibition poisoning.Chromatographic methods, notably gas and liquid chromatography have traditionally been employed to analyse carbamate pesticides and their metabolites in various matrices. These approaches are employed due to their ability to separate the chemicals contained in a sample; as well as identify and quantify these compounds utilizing advanced detection systems. Aside from these GC and LC conventional methods, other detection and/or hyphenated techniques such as single-quadrupole, ion-trap, triple-quadrupole, or tandem mass spectrometry, have been used in carbamate analysis to provide quick results with excellent sensitivity, precision, and accuracy.The objective of this review is to describe various analytical techniques used to detect and determine carbamate pesticides in various matrices which include urine, blood, and tissues that are commonly encountered in emergency hospital laboratories and forensic science laboratories.
Topics: Animals; Humans; Acetylcholinesterase; Carbamates; Carbaryl; Carbofuran; Forensic Toxicology; Insecticides; Pesticides
PubMed: 36399917
DOI: 10.1016/j.jflm.2022.102450 -
Human Molecular Genetics Mar 2023The principal component of the protein homeostasis network is the ubiquitin-proteasome system. Ubiquitination is mediated by an enzymatic cascade involving, i.e. E3...
The principal component of the protein homeostasis network is the ubiquitin-proteasome system. Ubiquitination is mediated by an enzymatic cascade involving, i.e. E3 ubiquitin ligases, many of which belong to the cullin-RING ligases family. Genetic defects in the ubiquitin-proteasome system components, including cullin-RING ligases, are known causes of neurodevelopmental disorders. Using exome sequencing to diagnose a pediatric patient with developmental delay, pyramidal signs and limb ataxia, we identified a de novo missense variant c.376G>C; p.(Asp126His) in the FEM1C gene encoding a cullin-RING ligase substrate receptor. This variant alters a conserved amino acid located within a highly constrained coding region and is predicted as pathogenic by most in silico tools. In addition, a de novo FEM1C mutation of the same residue p.(Asp126Val) was associated with an undiagnosed developmental disorder, and the relevant variant (FEM1CAsp126Ala) was found to be functionally compromised in vitro. Our computational analysis showed that FEM1CAsp126His hampers protein substrate binding. To further assess its pathogenicity, we used the nematode Caenorhabditis elegans. We found that the FEM-1Asp133His animals (expressing variant homologous to the FEM1C p.(Asp126Val)) had normal muscle architecture yet impaired mobility. Mutant worms were sensitive to the acetylcholinesterase inhibitor aldicarb but not levamisole (acetylcholine receptor agonist), showing that their disabled locomotion is caused by synaptic abnormalities and not muscle dysfunction. In conclusion, we provide the first evidence from an animal model suggesting that a mutation in the evolutionarily conserved FEM1C Asp126 position causes a neurodevelopmental disorder in humans.
Topics: Animals; Humans; Child; Proteasome Endopeptidase Complex; Cullin Proteins; Acetylcholinesterase; Speech; Ubiquitin-Protein Ligases; Neurodevelopmental Disorders; Ubiquitin; Caenorhabditis elegans; Ataxia; Ubiquitin-Protein Ligase Complexes
PubMed: 36336956
DOI: 10.1093/hmg/ddac276 -
Environmental Pollution (Barking, Essex... Dec 2022The environmental pollution caused by toxic chemicals such as pesticides has become a global problem. The mixture of dichlorvos (DIC), dimethoate (DIM), aldicarb (ALD)...
The environmental pollution caused by toxic chemicals such as pesticides has become a global problem. The mixture of dichlorvos (DIC), dimethoate (DIM), aldicarb (ALD) poses potential risks to the environment and human health. To fully explore the interaction of complex mixtures on Caenorhabditis elegans behavioral toxicity endpoint. This study created a synergistic-antagonistic heatmap (SAHmap) based on the combination index to systematically describe the toxicological interaction prospect of the mixture system. It was shown that the three pesticides and their binary as well as ternary mixture rays have significant concentration-response relationship on three behavioral endpoints of nematodes, From the perspective of synergistic-antagonistic heatmaps, all the mixture rays in the DIC-DIM mixture system showed strong synergism on the three behavioral and lethal endpoints. In the ternary mixture system, the five mixture rays showed different interaction between the behavioral endpoint and the lethal endpoint, and showed slight synergism to two behavioral endpoints as a whole. The emergence of synergism should arouse our attention to these hazardous chemicals. In addition, the use of SAHmap and the significant linear correlation among three behavioral endpoints further improved the efficiency of the study on the behavioral toxicity of pesticide mixtures to Caenorhabditis elegans.
Topics: Animals; Humans; Pesticides; Caenorhabditis elegans; Dichlorvos; Dimethoate
PubMed: 36220575
DOI: 10.1016/j.envpol.2022.120378 -
Journal of Food Science Oct 2022Pesticide residues in radishes can induce serious health hazards, especially in children and toddlers. In order to assess potential health risk from pesticide residues...
Pesticide residues in radishes can induce serious health hazards, especially in children and toddlers. In order to assess potential health risk from pesticide residues in radishes, a total of 26 pesticides were evaluated by gas chromatography with mass spectrometry in 1690 samples, which were collected from the year 2016 to 2019 in Shandong Province of China. All the 26 pesticide residues were detected in 752 radish samples (44.50%), but only 221 samples (13.08%) contained detectable pesticide residues, which are above the maximum residue limits (MRLs). Multiple residues with two to nine pesticides were present in 5.09% (86 out of 1690) of samples. Hazard quotient (HQ) and the cumulative risk index were far below 100, while percentage value of acute reference dose (%ARfD) of triazophos exceeded 100 for adults, children, and toddlers. The %ARfD value for carbofuran, aldicarb, monocrotophos, and parathion was over 100 for toddlers. From the perspective of public health, the occurrence of pesticide residues in radishes could not pose a serious health risk problem, but the acute health risk should be paid more attention, especially to toddlers. It is recommended to make strict regulations on the management of pesticide residues and human health risk assessment about pesticide residues.
Topics: Adult; Humans; Pesticide Residues; Raphanus; Carbofuran; Food Contamination; Aldicarb; Monocrotophos; Gas Chromatography-Mass Spectrometry; Risk Assessment; Pesticides; Parathion
PubMed: 36209472
DOI: 10.1111/1750-3841.16088