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Data in Brief Apr 2022Cytochrome P450 2B6 (CYP2B6) is a human enzyme important in chemical detoxification, steroid and fatty acid metabolism that is primarily hepatic. Therefore, induction or...
Cytochrome P450 2B6 (CYP2B6) is a human enzyme important in chemical detoxification, steroid and fatty acid metabolism that is primarily hepatic. Therefore, induction or inhibition of CYP2B6 may perturb endo- and xenobiotic metabolism and cause adverse reactions. Recent research indicates that mice lacking Cyp2b enzymes are obese with liver steatosis [1] (Heintz et al., , 70:125-137, 2019). Current work is underway to determine the role of CYP2B6 in obesity and fatty acid metabolism, and CYP2B6 fluorescent inhibition assays were used to determine the IC50s of multiple industrial chemicals, pesticides, bile acids, steroids, and fatty acids. In many cases, inhibition of CYP3A4 was also performed in comparison because CYP3A4 is the most abundant hepatic detoxification CYP and therefore by abundance alone may also play a key role in the chemical's metabolism. Further, using the ratio of comparative potency of these compounds for CYP2B6 and CYP3A4, specificity can be estimated for these CYP2B6 inhibitors. These results indicate strong preferential inhibition (greater than 10-fold) of CYP2B6 and include lithocholic acid, arachidonic acid, atrazine, chlorpyrifos, endosulfan, parathion, and nonylphenol. Estradiol was a strong preferential inhibitor of CYP3A4. Other screened CYP2B6 inhibitors include triclosan, ticlopidine, jet fuel, docosahexaenoic acid, linoleic acid, linolenic acid, oleic acid, lithocholic acid, butylate, hexachlorocyclohexane, vinclozolin, pentachlorophenol, metalachlor, butylate, diazinon, avermectin, tribufos, ticlopidine, and bisphenol A. Documentation of xenobiotic and endobiotic inhibition by these CYPs is necessary for proper modeling of the effects of diet, chemical exposure or even mixtures on drug metabolism and potential adverse reactions.
PubMed: 35282180
DOI: 10.1016/j.dib.2022.108013 -
Current Opinion in Structural Biology Aug 2021The evolution of novel enzymes has fueled the diversification of life on earth for billions of years. Insights into events that set the stage for the evolution of a new... (Review)
Review
The evolution of novel enzymes has fueled the diversification of life on earth for billions of years. Insights into events that set the stage for the evolution of a new enzyme can be obtained from ancestral reconstruction and laboratory evolution. Ancestral reconstruction can reveal the emergence of a promiscuous activity in a pre-existing protein and the impact of subsequent mutations that enhance a new activity. Laboratory evolution provides a more holistic view by revealing mutations elsewhere in the genome that indirectly enhance the level of a newly important enzymatic activity. This review will highlight recent studies that probe the early stages of the evolution of a new enzyme from these complementary points of view.
Topics: Evolution, Molecular; Mutation; Proteins
PubMed: 33865035
DOI: 10.1016/j.sbi.2021.03.001 -
Movement Disorders : Official Journal... May 2022Dream-enacting behavior is a characteristic feature of rapid eye movement sleep behavior disorder, the most specific prodromal marker of synucleinopathies. Pesticide...
BACKGROUND
Dream-enacting behavior is a characteristic feature of rapid eye movement sleep behavior disorder, the most specific prodromal marker of synucleinopathies. Pesticide exposure may be associated with dream-enacting behaviors, but epidemiological evidence is limited.
OBJECTIVES
To examine high pesticide exposure events in relation to dream-enacting behaviors among farmers in the Agricultural Health Study.
METHODS
We conducted multivariable logistic regression analyses to examine high pesticide exposure events reported from 1993 to 1997 in relation to dream-enacting behaviors assessed from 2013 to 2015 among 11,248 farmers (age 47 ± 11 years).
RESULTS
A history of dream-enacting behaviors was reported by 939 (8.3%) farmers. Compared with farmers who did not report any high pesticide exposure event, those who reported were more likely to endorse dream-enacting behaviors 2 decades later (odds ratio = 1.75; 95% confidence interval [CI], 1.49-2.05). The association appeared stronger when there was a long delay in washing with soap and water after the event (2.63 [95% CI, 1.62-4.27] for waiting >6 hours vs. 1.71 [95% CI, 1.36-2.15] for washing within 30 minutes) and when the exposure involved the respiratory or digestive tract (2.04 [95% CI, 1.62-2.57] vs. 1.58 [95% CI, 1.29-1.93] for dermal contact only). In the analyses of specific pesticides involved, we found positive associations with two organochlorine insecticides (dichlorodiphenyltrichloroethane and lindane), four organophosphate insecticides (phorate, ethoprop, terbufos, and parathion), two herbicides (alachlor and paraquat), and fungicides as a group.
CONCLUSIONS
This study provides the first epidemiological evidence that high pesticide exposures may be associated with a higher risk of dream-enacting behaviors. © 2022 International Parkinson and Movement Disorder Society.
Topics: Adult; Agriculture; Farmers; Humans; Insecticides; Middle Aged; Occupational Exposure; Pesticides
PubMed: 35152487
DOI: 10.1002/mds.28960 -
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 -
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 -
Journal of Pharmaceutical Analysis Aug 2022Balancing the risks and benefits of organophosphate pesticides (OPs) on human and environmental health relies partly on their accurate measurement. A highly sensitive...
Balancing the risks and benefits of organophosphate pesticides (OPs) on human and environmental health relies partly on their accurate measurement. A highly sensitive fluorescence anti-quenching multi-residue bio-barcode immunoassay was developed to detect OPs (triazophos, parathion, and chlorpyrifos) in apples, turnips, cabbages, and rice. Gold nanoparticles were functionalized with monoclonal antibodies against the tested OPs. DNA oligonucleotides were complementarily hybridized with an RNA fluorescent label for signal amplification. The detection signals were generated by DNA-RNA hybridization and ribonuclease H dissociation of the fluorophore. The resulting fluorescence signal enables multiplexed quantification of triazophos, parathion, and chlorpyrifos residues over the concentration range of 0.01-25, 0.01-50, and 0.1-50 ng/mL with limits of detection of 0.014, 0.011, and 0.126 ng/mL, respectively. The mean recovery ranged between 80.3% and 110.8% with relative standard deviations of 7.3%-17.6%, which correlate well with results obtained by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The proposed bio-barcode immunoassay is stable, reproducible and reliable, and is able to detect low residual levels of multi-residue OPs in agricultural products.
PubMed: 36105157
DOI: 10.1016/j.jpha.2022.05.004 -
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 -
Environment International Nov 2022Exposure of pet dogs and cats to pesticides used in and around homes (e.g., lawns and gardens) is a significant health concern. Furthermore, some pesticides are directly...
Exposure of pet dogs and cats to pesticides used in and around homes (e.g., lawns and gardens) is a significant health concern. Furthermore, some pesticides are directly used on dogs and cats for flea, lice, and tick control. Despite this, little is known regarding the extent of pesticide exposure in pets. In this study, we determined the concentrations of 30 biomarkers of pesticide exposure in urine collected from dogs and cats in New York State, USA: 6 dialkylphosphate (DAP) metabolites of organophosphates (OPs); 14 neonicotinoids (neonics); 3 specific metabolites of OPs; 5 pyrethroids (PYRs); and 2 phenoxy acids (PAs). The sum median concentrations of these 30 pesticide biomarkers (ΣPesticides) in dog and cat urine were 35.2 and 38.1 ng/mL, respectively. Neonics were the most prevalent in dogs (accounting for 43% of the total concentrations), followed by DAPs (17%), PYRs (16%), OPs (13%), and PAs (∼10%). In cat urine, neonics alone accounted for 83% of the total concentrations. Elevated concentrations of imidacloprid were found in the urine of certain dogs (max: 115 ng/mL) and cats (max: 1090 ng/mL). Some pesticides showed gender- and sampling location- related differences in urinary concentrations. We calculated daily exposure doses of pesticides from the measured urinary concentrations through a reverse dosimetry approach. The estimated daily intakes (DIs) of chlorpyrifos, diazinon, and cypermethrin were above the chronic reference doses (cRfDs) in 22, 76, and 5%, respectively, of dogs. The DIs of chlorpyrifos, parathion, diazinon, and imidacloprid were above the cRfDs in 33, 14, 100, and 29%, respectively, of cats. This study thus provides evidence that pet dogs and cats are exposed to certain pesticides at levels that warrant immediate attention.
Topics: Animals; Biomarkers; Cat Diseases; Cats; Chlorpyrifos; Diazinon; Dog Diseases; Dogs; Environmental Exposure; Neonicotinoids; New York; Nitro Compounds; Parathion; Pesticides; Pyrethrins; United States
PubMed: 36155914
DOI: 10.1016/j.envint.2022.107526