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Microorganisms Jun 2023The use of pesticides in agricultural practices raises concerns considering the toxic effects they generate in the environment; thus, their sustainable application in... (Review)
Review
The use of pesticides in agricultural practices raises concerns considering the toxic effects they generate in the environment; thus, their sustainable application in crop production remains a challenge. One of the frequently addressed issues regarding their application includes the development of a sustainable and ecofriendly approach for their degradation. Since the filamentous fungi can bioremediate various xenobiotics owing to their efficient and versatile enzymatic machinery, this review has addressed their performance in the biodegradation of organochlorine and organophosphorus pesticides. It is focused particularly on fungal strains belonging to the genera and , since both are ubiquitous in the environment, and often abundant in soils contaminated with xenobiotics. Most of the recent reviews on microbial biodegradation of pesticides focus primarily on bacteria, and the soil filamentous fungi are mentioned only marginally there. Therefore, in this review, we have attempted to demonstrate and highlight the exceptional potential of aspergilli and penicillia in degrading the organochlorine and organophosphorus pesticides (e.g., endosulfan, lindane, chlorpyrifos, and methyl parathion). These biologically active xenobiotics have been degraded by fungi into various metabolites efficaciously, or these are completely mineralized within a few days. Since they have demonstrated high rates of degradation activity, as well as high tolerance to pesticides, most of the and species strains listed in this review are excellent candidates for the remediation of pesticide-contaminated soils.
PubMed: 37374987
DOI: 10.3390/microorganisms11061485 -
Chemico-biological Interactions Nov 2016Paraoxonase-1 (PON1), an esterase/lactonase primarily associated with plasma high-density lipoprotein (HDL), was the first member of this family of enzymes to be...
Paraoxonase-1 (PON1), an esterase/lactonase primarily associated with plasma high-density lipoprotein (HDL), was the first member of this family of enzymes to be characterized. Its name was derived from its ability to hydrolyze paraoxon, the toxic metabolite of the insecticide parathion. Related enzymes PON2 and PON3 were named from their evolutionary relationship with PON1. Mice with each PON gene knocked out were generated at UCLA and have been key for elucidating their roles in organophosphorus (OP) metabolism, cardiovascular disease, innate immunity, obesity, and cancer. PON1 status, determined with two-substrate analyses, reveals an individual's functional Q192R genotype and activity levels. The three-dimensional structure for a chimeric PON1 has been useful for understanding the structural properties of PON1 and for engineering PON1 as a catalytic scavenger of OP compounds. All three PONs hydrolyze microbial N-acyl homoserine lactone quorum sensing factors, quenching Pseudomonas aeruginosa's pathogenesis. All three PONs modulate oxidative stress and inflammation. PON2 is localized in the mitochondria and endoplasmic reticulum. PON2 has potent antioxidant properties and is found at 3- to 4-fold higher levels in females than males, providing increased protection against oxidative stress, as observed in primary cultures of neurons and astrocytes from female mice compared with male mice. The higher levels of PON2 in females may explain the lower frequency of neurological and cardiovascular diseases in females and the ability to identify males but not females with Parkinson's disease using a special PON1 status assay. Less is known about PON3; however, recent experiments with PON3 knockout mice show them to be susceptible to obesity, gallstone formation and atherosclerosis. Like PONs 1 and 2, PON3 also appears to modulate oxidative stress. It is localized in the endoplasmic reticulum, mitochondria and on HDL. Both PON2 and PON3 are upregulated in cancer, favoring tumor progression through mitochondrial protection against oxidative stress and apoptosis.
Topics: Animals; Aryldialkylphosphatase; Astrocytes; Carotid Artery Diseases; Cells, Cultured; Clopidogrel; Endoplasmic Reticulum; Female; Genotype; Homocysteine; Humans; Inflammation; Lipid Metabolism; Lipoproteins, HDL; Male; Mice; Mice, Knockout; Mitochondria; Neurons; Organophosphorus Compounds; Oxidative Stress; Platelet Aggregation Inhibitors; Quorum Sensing; Ticlopidine
PubMed: 27238723
DOI: 10.1016/j.cbi.2016.05.036 -
British Journal of Clinical Pharmacology Dec 2022Organophosphorus (OP) insecticide poisoning causes respiratory failure due to acetylcholinesterase (AChE) inhibition. The AChE reactivating antidote pralidoxime was...
Organophosphorus (OP) insecticide poisoning causes respiratory failure due to acetylcholinesterase (AChE) inhibition. The AChE reactivating antidote pralidoxime was developed in the 1950s and was soon noted to benefit patients occupationally poisoned with the highly potent OP insecticide parathion. Routine use of pralidoxime and other oximes such as obidoxime then became widely recommended. However, nearly all severe cases of OP poisoning now result from self-poisoning with large volumes of less potent (WHO hazard class Ib and II) insecticides and co-formulated solvents. Unfortunately, oxime clinical trials have never shown benefit from their use for these patients, and some have shown that pralidoxime may be associated with harm, including increased mortality. Oximes should not be used routinely for the care of OP insecticide-poisoned patients until translational and clinical studies have identified a safe and effective oxime regimen and identified the patients who benefit.
Topics: Humans; Insecticides; Oximes; Acetylcholinesterase; Organophosphorus Compounds; Organophosphate Poisoning; Cholinesterase Inhibitors; Poisoning
PubMed: 34989015
DOI: 10.1111/bcp.15217 -
Environment International Sep 2018Little is known about modifiable risk factors for thyroid disease. Several pesticides have been implicated in thyroid disruption, but clinical implications are not clear.
BACKGROUND
Little is known about modifiable risk factors for thyroid disease. Several pesticides have been implicated in thyroid disruption, but clinical implications are not clear.
OBJECTIVE
We assessed associations between pesticide use and other farm exposures and incident hypothyroidism and hyperthyroidism in female spouses of farmers in the Agricultural Health Study (AHS).
METHODS
We used Cox proportional hazards models to estimate hazard ratios (HR) and 95% confidence intervals for risk of thyroid disease in 24,092 spouses who completed at least one follow-up questionnaire.
RESULTS
We identified 1627 hypothyroid and 531 hyperthyroid cases over 20 years of follow-up. The fungicides benomyl, maneb/mancozeb, and metalaxyl, the herbicide pendimethalin, and among those over 60 years of age the insecticides parathion and permethrin (applied to crops) were associated with elevated hypothyroidism risk, with HR ranging from 1.56-2.44. Conversely, the insecticide phorate, and the herbicides imazethapyr and metolachlor were associated with decreased risk (HR ranging 0.63-0.73), as were long-term farm residence and other farm-related activities (HR ranging 0.69-0.84). For hyperthyroidism, the insecticide diazinon, the fungicides maneb/mancozeb, and the herbicide metolachlor were associated with increased risk (HR ranging 1.35-2.01) and the herbicide trifluralin with decreased risk (HR: 0.57).
CONCLUSIONS
Several individual pesticides were associated with increased risk of hypothyroidism and hyperthyroidism, although some pesticides were associated with decreased risk. Some of the findings, specifically associations with fungicides, are consistent with results from an earlier analysis of prevalent diseases in AHS spouses.
Topics: Female; Follow-Up Studies; Humans; Male; Occupational Exposure; Pesticides; Spouses; Surveys and Questionnaires; Thyroid Diseases
PubMed: 29908479
DOI: 10.1016/j.envint.2018.05.041 -
Children (Basel, Switzerland) Nov 2021Brain tumors are the second most common neoplasm in the pediatric age. Pesticides may play an etiologic role, but literature results are conflicting. This review... (Review)
Review
Parental Pesticide Exposure and Childhood Brain Cancer: A Systematic Review and Meta-Analysis Confirming the IARC/WHO Monographs on Some Organophosphate Insecticides and Herbicides.
BACKGROUND
Brain tumors are the second most common neoplasm in the pediatric age. Pesticides may play an etiologic role, but literature results are conflicting. This review provides a systematic overview, meta-analysis, and IARC/WHO consideration of data on parental exposure to pesticides and childhood brain tumors.
METHODS
We searched PubMed, SCOPUS, and Google Scholar for literature (1 January 1966-31 December 2020) that assessed childhood brain tumors and parental exposure to pesticides. We undertook a meta-analysis addressing prenatal exposure, exposure after birth, occupational exposure, and residential exposure. A total of 130 case-control investigations involving 43,598 individuals (18,198 cases and 25,400 controls) were included.
RESULTS
Prenatal exposure is associated with childhood brain tumors (odds ratio, OR = 1.32; 95% CI: 1.17-1.49; I = 41.1%). The same occurs after birth exposure (OR = 1.22; 95% CI: 1.03-1.45, I = 72.3%) and residential exposure to pesticides (OR = 1.31; 95% CI: 1.11-1.54, I = 67.2%). Parental occupational exposure is only marginally associated with CBT (OR = 1.17, 95% CI: 0.99-1.38, I = 67.0%).
CONCLUSIONS
There is an association between CBT and parental pesticides exposure before childbirth, after birth, and residential exposure. It is in line with the IARC Monograph evaluating the carcinogenicity of diazinon, glyphosate, malathion, parathion, and tetrachlorvinphos.
PubMed: 34943292
DOI: 10.3390/children8121096 -
Applied and Environmental Microbiology Oct 2021-Nitrophenol (PNP) is a hydrolytic product of organophosphate insecticides, such as parathion and methylparathion, in soil. Aerobic microbial degradation of PNP has been...
-Nitrophenol (PNP) is a hydrolytic product of organophosphate insecticides, such as parathion and methylparathion, in soil. Aerobic microbial degradation of PNP has been classically shown to proceed via the "hydroquinone (HQ) pathway" in Gram-negative degraders, whereas it proceeds via the "benzenetriol (BT) pathway" in Gram-positive ones. The "HQ pathway" is initiated by a single-component PNP 4-monooxygenase and the "BT pathway" by a two-component PNP 2-monooxygenase. Their regioselectivity intrigued us enough to investigate their catalytic difference through structural study. PnpA1 is the oxygenase component of the two-component PNP 2-monooxygenase from Gram-positive Rhodococcus imtechensis strain RKJ300. It also catalyzes the hydroxylation of 4-nitrocatechol (4NC) and 2-chloro-4-nitrophenol (2C4NP). However, the mechanisms are unknown. Here, PnpA1 was structurally determined to be a member of the group D flavin-dependent monooxygenases with an acyl coenzyme A (acyl-CoA) dehydrogenase fold. The crystal structure and site-directed mutagenesis underlined the direct involvement of Arg100 and His293 in catalysis. The bulky side chain of Val292 was proposed to push the substrate toward flavin adenine dinucleotide (FAD), hence positioning the substrate properly. An N450A variant was found with improved activity for 4NC and 2C4NP-probably because of the reduced steric hindrance. PnpA1 shows an obvious difference in substrate selectivity with its close homologues TcpA and TftD, which may be caused by the unique Thr296 and a different conformation in the loop from positions 449 to 454 (loop 449-454). Above all, our study allows structural comparison between the two types of PNP monooxygenases. An explanation that accounts for their regioselectivity was proposed: the different PNP binding manners determine their choice of - or -hydroxylation on PNP. Single-component PNP monoxygenases hydroxylate PNP at the 4 position, while two-component ones do so at the 2 position. However, their catalytic and structural differences remain elusive. The structure of single-component PNP 4-monooxygenase has previously been determined. In this study, to illustrate their catalytic difference, we resolved the crystal structure of PnpA1, a typical two-component PNP 2-monooxygenase. The roles of several key amino acid residues in substrate binding and catalysis were revealed, and a variant with improved activities toward 4NC and 2C4NP was obtained. Moreover, through comparison of the two types of PNP monooxygenases, a hypothesis was proposed to account for their catalytic difference, which gives us a better understanding of these two similar reactions at the molecular level. In addition, these results will also be of further aid in rational design of enzymes in bioremediation and biosynthesis.
Topics: Bacterial Proteins; Catalysis; Mixed Function Oxygenases; Nitrophenols; Rhodococcus
PubMed: 34469195
DOI: 10.1128/AEM.01171-21 -
Toxicology Reports 2022Organophosphorus pesticides (OPPs) cause great risk to human health as they are used globally. Therefore, the purpose of this research was to determine the total...
Organophosphorus pesticides (OPPs) cause great risk to human health as they are used globally. Therefore, the purpose of this research was to determine the total phenolics, flavonoids, and antioxidant activity of agricultural waste, as well as to control the pesticide residues (diazinon, and parathion) at a laboratory scale level using dried-milled fruit wastes. The pesticide residues parathion and diazinon were used at concentrations of 0.094, and 1.90 mg/mL respectively. The fruit wastes used in this study were orange and banana peels, as well as date stones, and they were used in two concentrations (3 and 9 g/30 mL deionized water). The total phenolic and flavonoid contents and the antioxidant activity were measured in fruit wastes. Also, the Fourier transmitted infrared (FTIR) spectra of fruit wastes were established to figure out the nature of the functional groups found before and after pesticide residues removal. The ability of fruit wastes to remove pesticides residues was determined using Gas Chromatography/Mass spectrometry (GC/MS). Data showed that date stones contained a higher amount of total phenolic content than orange and banana peels. However, orange peels contained a higher amount of total flavonoid contents than those of date stones and banana peels. As for antioxidant activity, banana peels recorded the higher antioxidant activity, followed by orange peels and date stones respectively. Results revealed that there was no relation between total phenolic content, total flavonoid content, and antioxidant activity. Results also indicated that date stones at a concentration of 9 g successfully reduced diazinon (81.18%), followed by banana (63.86%) and orange peels (43.42%) respectively, whereas parathion was reduced by banana peels at a concentration of 9 g (50.34%), followed by orange peels (45.28%), and date stones (39.52%) respectively. This study demonstrated that agricultural wastes were effective in the adsorption of diazinon from water, and their use is considered safe for the environment.
PubMed: 35399213
DOI: 10.1016/j.toxrep.2022.03.038 -
G3 (Bethesda, Md.) Nov 2018Resistance to insecticides has evolved in multiple insect species, leading to increased application rates and even control failures. Understanding the genetic basis of...
Resistance to insecticides has evolved in multiple insect species, leading to increased application rates and even control failures. Understanding the genetic basis of insecticide resistance is fundamental for mitigating its impact on crop production and disease control. We performed a GWAS approach with the Genetic Reference Panel (DGRP) to identify the mutations involved in resistance to two widely used classes of insecticides: organophosphates (OPs, parathion) and pyrethroids (deltamethrin). Most variation in parathion resistance was associated with mutations in the target gene , while most variation in deltamethrin resistance was associated with mutations in , a gene encoding a detoxification enzyme never previously associated with resistance. A "nested GWAS" further revealed the contribution of other loci: and were implicated in resistance to parathion, but only in lines lacking , the paralogous gene of , and , an ATP-binding cassette transporter, were implicated in deltamethrin resistance. We observed signatures of recent selective sweeps at all of these resistance loci and confirmed that the soft sweep at is indeed driven by the identified resistance mutations. Analysis of allele frequencies in additional population samples revealed that most resistance mutations are segregating across the globe, but that frequencies can vary substantially among populations. Altogether, our data reveal that the widely used OP and pyrethroid insecticides imposed a strong selection pressure on natural insect populations. However, it remains unclear why, in , resistance evolved due to changes in the target site for OPs, but due to a detoxification enzyme for pyrethroids.
Topics: Animals; Drosophila melanogaster; Female; Genetic Variation; Genome, Insect; Genome-Wide Association Study; Insecticide Resistance; Insecticides; Male; Organophosphates; Pyrethrins; Selection, Genetic
PubMed: 30190420
DOI: 10.1534/g3.118.200537 -
Frontiers in Microbiology 2022Organophosphate compounds are widely used in pesticides to control weeds, crop diseases, and insect pests. Unfortunately, these synthetic compounds are hazardous and...
Organophosphate compounds are widely used in pesticides to control weeds, crop diseases, and insect pests. Unfortunately, these synthetic compounds are hazardous and toxic to all types of living organisms. In the present work, was bioengineered to achieve methyl parathion (MP) degradation via the introduction of six synthetic genes, namely, , , , , , and , to obtain a new transformant, BL-MP. MP and its subsequent decomposition intermediates were completely degraded by this transformant to enter the metabolites of multiple anabolic pathways. The MP-degraded strain created in this study may be a promising candidate for the bioremediation of MP and potential toxic intermediates.
PubMed: 35222319
DOI: 10.3389/fmicb.2022.679126 -
Neurotoxicology Mar 2021Due to the increasing number of drugs and untested environmental compounds introduced into commercial use, there is recognition for a need to develop reliable and... (Comparative Study)
Comparative Study
Due to the increasing number of drugs and untested environmental compounds introduced into commercial use, there is recognition for a need to develop reliable and efficient screening methods to identify compounds that may adversely impact the nervous system. One process that has been implicated in neurodevelopment is neurite outgrowth; the disruption of which can result in adverse outcomes that persist later in life. Here, we developed a green fluorescent protein (GFP) labeled neurite outgrowth assay in a high-content, high-throughput format using induced pluripotent stem cell (iPSC) derived human spinal motor neurons and cortical glutamatergic neurons. The assay was optimized for use in a 1536-well plate format. Then, we used this assay to screen a set of 84 unique compounds that have previously been screened in other neurite outgrowth assays. This library consists of known developmental neurotoxicants, environmental compounds with unknown toxicity, and negative controls. Neurons were cultured for 40 h and then treated with compounds at 11 concentrations ranging from 1.56 nM to 92 μM for 24 and 48 h. Effects of compounds on neurite outgrowth were evaluated by quantifying total neurite length, number of segments, and maximum neurite length per cell. Among the 84 tested compounds, neurite outgrowth in cortical neurons and motor neurons were selectively inhibited by 36 and 31 compounds, respectively. Colchicine, rotenone, and methyl mercuric (II) chloride inhibited neurite outgrowth in both cortical and motor neurons. It is interesting to note that some compounds like parathion and bisphenol AF had inhibitory effects on neurite outgrowth specifically in the cortical neurons, while other compounds, such as 2,2',4,4'-tetrabromodiphenyl ether and caffeine, inhibited neurite outgrowth in motor neurons. The data gathered from these studies show that GFP-labeled iPSC-derived human neurons are a promising tool for identifying and prioritizing compounds with developmental neurotoxicity potential for further hazard characterization.
Topics: Cell Line; Genes, Reporter; Green Fluorescent Proteins; High-Throughput Screening Assays; Humans; Induced Pluripotent Stem Cells; Neural Stem Cells; Neuronal Outgrowth; Neurons; Risk Assessment; Toxicity Tests
PubMed: 33508353
DOI: 10.1016/j.neuro.2021.01.003