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Parasites & Vectors Sep 2012Carboxylesterase overproduction is a frequently observed resistance mechanism of insects to organophosphate insecticides. As a major transmitter of human diseases,...
BACKGROUND
Carboxylesterase overproduction is a frequently observed resistance mechanism of insects to organophosphate insecticides. As a major transmitter of human diseases, mosquitoes in the Culex pipiens complex have evolved 13 carboxylesterase alleles (Ester) that confer organophosphate resistance. Six alleles, Ester(B1), Ester², Ester⁸, Ester⁹, Ester(B10), and Ester¹¹, have been observed in field populations in China, sometimes co-existing in one population. To differentiate the carboxylesterase alleles found in these field populations, PCR-RFLP was designed for use in resistance monitoring.
RESULTS
Based on the DNA sequences of resistant and nonresistant carboxylesterase alleles, Ester B alleles were first amplified with PCR-specific primers and then digested with the restriction enzyme DraI. In this step, Ester² and Ester¹¹ were differentiated from the other Ester alleles. When the other Ester B alleles were digested with the restriction enzyme XbaI, Ester(B1) and the susceptible C. p. pallens Ester were screened out. Ester⁸ and Ester⁹ were differentiated from Ester(B10) and the susceptible C. p. quinquefasciatus esterase allele, respectively, by amplifying and digesting the Ester A alleles with the restriction enzyme ApaLI. The effectiveness of the custom-designed PCR-RFLP was verified in two field mosquito populations.
CONCLUSIONS
A PCR-RFLP based approach was developed to differentiate carboxylesterase alleles in Culex pipiens complex mosquitoes. These processes may be useful in monitoring the evolutionary dynamics of known carboxylesterase alleles as well as in the identification of new alleles in field populations.
Topics: Alleles; Animals; Carboxylesterase; China; Culex; Disease Vectors; Entomology; Insecticide Resistance; Organophosphates; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length
PubMed: 23006470
DOI: 10.1186/1756-3305-5-209 -
European Review For Medical and... Jan 2022The organophosphate compounds chlorpyrifos (O, O-diethyl O-[3,5,6-trichloro-2-pyridinyl] phosphorothioate, CPF) and phenyl saligenin phosphate (PSP) have been widely...
OBJECTIVE
The organophosphate compounds chlorpyrifos (O, O-diethyl O-[3,5,6-trichloro-2-pyridinyl] phosphorothioate, CPF) and phenyl saligenin phosphate (PSP) have been widely implicated in developmental neurotoxicity and neurodegeneration. However, the underlying mechanism remains unclear. Transglutaminase (TG)2 is a calcium ion (Ca2+)-dependent enzyme with an important role in neuronal cell outgrowth and differentiation and in neurotoxin activity and is modulated by organophosphates.
MATERIALS AND METHODS
We studied TG2 activity modulation by CPO and PSP during differentiation in C6 glioma cells. We studied the effects of CPO or PSP treatment with or without the TG2 inhibitor Z-DON and identified potential TG2 protein substrates via mass spectrometry.
RESULTS
PSP and CPO did not affect cell viability but affected TG2 activity in differentiating cells. Our results indicate that the organophosphate-induced amine incorporation activity of TG2 may have a direct effect on neuronal outgrowth, differentiation, and cell survival by modifying several essential microtubule proteins, including tubulin. Inhibiting TG2 reduced neurite length but not cell survival.
CONCLUSIONS
TG2 inhibitors can protect against organophosphate-induced neuropathy and could be used for developing novel therapeutic strategies for treating brain cancer and neurodegenerative disorders.
Topics: Animals; Cell Differentiation; GTP-Binding Proteins; Organophosphates; Protein Glutamine gamma Glutamyltransferase 2; Rats; Transglutaminases
PubMed: 35049033
DOI: 10.26355/eurrev_202201_27766 -
Frontiers in Public Health 2023The relationship between exposure to organophosphate esters (OPEs) and the risk of developing overactive bladder (OAB) is uncertain. The purpose of this study is to...
BACKGROUND
The relationship between exposure to organophosphate esters (OPEs) and the risk of developing overactive bladder (OAB) is uncertain. The purpose of this study is to examine the potential link between urinary metabolites of organophosphate esters and OAB.
METHOD
Data from the National Health and Nutrition Examination Survey (NHANES) database of the 2011-2016 cycles were utilized. Four urinary metabolites of organophosphate esters: diphenyl phosphate (DPHP), bis (1,3-dichloro-2-propyl) phosphate (BDCPP), bis (2-chloroethyl) phosphate (BCEP), and dibutyl phosphate (DBUP) were included in the study. Multivariate logistic regression and restricted cubic spline (RCS) were used to evaluate the relationship between urinary OPEs metabolites and OAB. Interaction analysis was conducted on subgroups to confirm the findings.
RESULTS
A total of 3,443 United States (US) adults aged 20 years or older were included in the study, of whom 597 participants were considered to have OAB. After adjusting for potential confounding factors, we found a positive association between DPHP and the risk of overactive bladder. The risk of overactive bladder increased with increasing DPHP concentrations compared with quartile 1 (quartile 2, OR = 1.19, 95% CI, 0.82-1.73, = 0.34; quartile 3, OR = 1.67, 95% CI, 1.10-2.53, = 0.02; Q4, OR = 1.75, 95% CI, 1.26-2.43, = 0.002). However, after dividing the participants by gender, only the female group retained consistent results. Additionally, restricted cubic spline analysis revealed a nonlinear dose-response correlation between DPHP and OAB in female participants. In the subgroup analysis based on age, race, body mass index (BMI), recreational activity, smoking status, drinking status, hypertension, diabetes, and stroke, the interaction analysis revealed that the findings were uniform.
CONCLUSION
Our findings indicate that exposure to DPHP could elevate the risk of OAB in US adult females. Further experimental studies are needed to explore the underlying mechanism in the future.
Topics: Humans; Adult; United States; Female; Cross-Sectional Studies; Nutrition Surveys; Urinary Bladder, Overactive; Organophosphates; Phosphates
PubMed: 38026372
DOI: 10.3389/fpubh.2023.1186848 -
Proceedings of the National Academy of... Oct 2019Insecticides allow control of agricultural pests and disease vectors and are vital for global food security and health. The evolution of resistance to insecticides, such...
Insecticides allow control of agricultural pests and disease vectors and are vital for global food security and health. The evolution of resistance to insecticides, such as organophosphates (OPs), is a serious and growing concern. OP resistance often involves sequestration or hydrolysis of OPs by carboxylesterases. Inhibiting carboxylesterases could, therefore, restore the effectiveness of OPs for which resistance has evolved. Here, we use covalent virtual screening to produce nano-/picomolar boronic acid inhibitors of the carboxylesterase αE7 from the agricultural pest as well as a common Gly137Asp αE7 mutant that confers OP resistance. These inhibitors, with high selectivity against human acetylcholinesterase and low to no toxicity in human cells and in mice, act synergistically with the OPs diazinon and malathion to reduce the amount of OP required to kill by up to 16-fold and abolish resistance. The compounds exhibit broad utility in significantly potentiating another OP, chlorpyrifos, against the common pest, the peach-potato aphid (). These compounds represent a solution to OP resistance as well as to environmental concerns regarding overuse of OPs, allowing significant reduction of use without compromising efficacy.
Topics: Acetylcholinesterase; Animals; Aphids; Carboxylic Ester Hydrolases; Cell Line; Diazinon; Female; HEK293 Cells; Humans; Insecticide Resistance; Insecticides; Malathion; Mice; Mice, Inbred C57BL; Organophosphates
PubMed: 31575743
DOI: 10.1073/pnas.1909130116 -
Drug Design, Development and Therapy 2013Tedizolid phosphate (TR-701), a prodrug of tedizolid (TR-700), is a next-generation oxazolidinone that has shown favorable results in the treatment of acute bacterial... (Comparative Study)
Comparative Study Review
Tedizolid phosphate (TR-701), a prodrug of tedizolid (TR-700), is a next-generation oxazolidinone that has shown favorable results in the treatment of acute bacterial skin and skin-structure infections in its first Phase III clinical trial. Tedizolid has high bioavailability, penetration, and tissue distribution when administered orally or intravenously. The activity of tedizolid was greater than linezolid against strains of Staphylococcus spp., Streptococcus spp., and Enterococcus spp. in vitro studies, including strains resistant to linezolid and those not susceptible to vancomycin or daptomycin. Its pharmacokinetic characteristics allow for a once-daily administration that leads to a more predictable efficacy and safety profile than those of linezolid. No hematological adverse effects have been reported associated with tedizolid when used at the therapeutic dose of 200 mg in Phase I, II, or III clinical trials of up to 3 weeks of tedizolid administration. Given that the clinical and microbiological efficacy are similar for the 200, 300, and 400 mg doses, the lowest effective dose of 200 mg once daily for 6 days was selected for Phase III studies in acute bacterial skin and skin-structure infections, providing a safe dosing regimen with low potential for development of myelosuppression. Unlike linezolid, tedizolid does not inhibit monoamine oxidase in vivo, therefore interactions with adrenergic, dopaminergic, and serotonergic drugs are not to be expected. In conclusion, tedizolid is a novel antibiotic with potent activity against Gram-positive microorganisms responsible for skin and soft tissue infections, including strains resistant to vancomycin, linezolid, and daptomycin, thus answers a growing therapeutic need.
Topics: Acute Disease; Animals; Anti-Bacterial Agents; Biological Availability; Drug Resistance, Bacterial; Gram-Positive Bacteria; Humans; Organophosphates; Oxazoles; Skin Diseases, Bacterial; Soft Tissue Infections; Tissue Distribution
PubMed: 23589680
DOI: 10.2147/DDDT.S30728 -
Biochemistry Mar 2020Organophosphate flame retardants are used to inhibit combustion and increase plasticity in plastics and durable foams. While not neurotoxic, these compounds are...
Organophosphate flame retardants are used to inhibit combustion and increase plasticity in plastics and durable foams. While not neurotoxic, these compounds are potential carcinogens, endocrine disrupters, and developmental toxins. The phosphotriesterase from sp. TCM1 (-PTE) is unique among phosphotriesterase enzymes for its ability to hydrolyze these compounds and its ability to hydrolyze any one of the three different ester bonds within a given substrate. In some cases, the extent of hydrolysis of a methyl ester exceeds that of a -nitrophenyl ester within a single substrate. There is a stereochemical component to this hydrolysis where the two enantiomers of chiral substrates give different product ratios. To investigate the stereoselectivity for the product distribution of -PTE, a series of 24 phosphotriesters were synthesized with all possible combinations of methyl, cyclohexyl, phenyl, and -nitrophenyl esters. Prochiral compounds were made chiral by differential isotopic labeling using a chemo/enzymatic strategy, which allowed the differentiation of hydrolysis for each ester in all but two compounds. The rate equations for this unique enzymatic mechanism were derived; the product ratios were determined for each substrate, and the individual kinetic constants for hydrolysis of each ester within each substrate were measured. The findings are consistent with the rate-limiting step for substrate hydrolysis catalyzed by -PTE being the formation of a phosphorane-like intermediate and the kinetic constants and product ratios being dictated by a combination of transition state energies, inductive effects, and stereochemical constraints.
Topics: Biocatalysis; Biodegradation, Environmental; Environmental Pollutants; Flame Retardants; Hydrolysis; Kinetics; Organophosphates; Phosphoric Triester Hydrolases; Sphingomonadaceae; Stereoisomerism; Substrate Specificity
PubMed: 32167750
DOI: 10.1021/acs.biochem.0c00089 -
Environmental Science & Technology Jan 2022Occupational exposures to flame retardants (FRs), a class of suspected endocrine-disrupting compounds, are of health concern for firefighters. We sought to characterize...
Organophosphate and Organohalogen Flame-Retardant Exposure and Thyroid Hormone Disruption in a Cross-Sectional Study of Female Firefighters and Office Workers from San Francisco.
Occupational exposures to flame retardants (FRs), a class of suspected endocrine-disrupting compounds, are of health concern for firefighters. We sought to characterize exposure to FR compounds and evaluate their association with thyroid hormone levels, a biomarker of early effect, in female firefighters and office workers in San Francisco. In a cross-sectional study, we measured replacement organophosphate and organohalogen FRs in spot urine samples from firefighters ( = 86) and office workers ( = 84), as well as total thyroxine (T) and thyroid-stimulating hormone in plasma for 84 firefighters and 81 office workers. Median bis(1,3-dichloro-2-propyl)phosphate (BDCPP) levels were 5 times higher in firefighters than office workers. Among firefighters, a doubling of BDCPP was associated with a 2.88% decrease (95% confidence interval -5.28, -0.42) in T. We did not observe significant associations between FRs and T among office workers. In the full group, intermediate body mass index and a college education were associated with higher FR levels. The inverse association observed between FRs and T coupled with the lack of studies on women workers and evidence of adverse health effects from FR exposure─including endocrine disruption and breast cancer risk─warrant further research on occupational exposures and identification of opportunities for exposure reduction.
Topics: Cross-Sectional Studies; Female; Firefighters; Flame Retardants; Humans; Organophosphates; San Francisco; Thyroid Hormones
PubMed: 34902963
DOI: 10.1021/acs.est.1c05140 -
Ecotoxicology and Environmental Safety Dec 2023Organophosphorus flame retardants (OPFRs) have been shown to be carcinogenic, neurotoxic, and endocrine disruptive, so it is important to understand the levels of OPFRs...
Organophosphorus flame retardants (OPFRs) have been shown to be carcinogenic, neurotoxic, and endocrine disruptive, so it is important to understand the levels of OPFRs in human body as well as the modes of external exposure. In this study, we investigated the levels of 13 OPFRs and 7 phosphodiester metabolites in paired human blood and urine, as well as the influencing factors (region, age and gender), and studied the relationship between OPFRs and oxidative stress by urinary metabolites. We found that the concentrations of triphenyl phosphate (TPhP) and tris-(2-ethylhexyl) phosphate (TEHP) in the blood of urban populations were higher than those of rural populations, and that younger populations suffered higher TPhP and 2-ethylhexyl diphenyl phosphate (EHDPP) exposures than older populations. In addition, we found that tris-(2-chloroethyl) phosphate (TCEP), tributyl phosphate (TnBP), TPhP and EHDPP exposure induced oxidative stress. The results of the internal load principal component analysis indicated that dust ingestion, skin exposure, respiration and dietary intake may be the most important sources of TCEP, tris(2-butoxyethyl) phosphate (TBOEP), tri(2-chloroisopropyl) phosphate (TCIPP) and TEHP, respectively, and dust ingestion and skin exposure may be the main sources of TPhP for humans.
Topics: Humans; Flame Retardants; Organophosphorus Compounds; Organophosphates; Dust; Phosphates
PubMed: 37979363
DOI: 10.1016/j.ecoenv.2023.115696 -
Biosensors Feb 2019Pesticides, due to their intensive use and their peculiar chemical features, can persist in the environment and enter the trophic chain, thus representing an... (Review)
Review
Pesticides, due to their intensive use and their peculiar chemical features, can persist in the environment and enter the trophic chain, thus representing an environmental risk for the ecosystems and human health. Although there are several robust and reliable standard analytical techniques for their monitoring, the high frequency of contamination caused by pesticides requires methods for massive monitoring campaigns that are capable of rapidly detecting these compounds in many samples of different origin. Immunosensors represent a potential tool for simple, rapid, and sensitive monitoring of pesticides. Antibodies coupled to electrochemical or optical transducers have resulted in effective detection devices. In this review, the new trends in immunosensor development and the application of immunosensors for the detection of pesticides of environmental concern-such as glyphosate, organophosphates, and neonicotinoids-are described.
Topics: Antibodies; Biosensing Techniques; Glycine; Neonicotinoids; Organophosphates; Pesticides; Glyphosate
PubMed: 30720729
DOI: 10.3390/bios9010020 -
Environmental Health Perspectives Aug 2011
Topics: Cognition; Environmental Exposure; Female; Humans; Organophosphates; Pesticides; Pregnancy; Prenatal Exposure Delayed Effects
PubMed: 21807587
DOI: 10.1289/ehp.1104137