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The Journal of Pharmacology and... Jan 2024Organophosphate (OP) poisoning can trigger cholinergic crisis, a life-threatening toxidrome that includes seizures and status epilepticus. These acute toxic responses... (Review)
Review
Organophosphate (OP) poisoning can trigger cholinergic crisis, a life-threatening toxidrome that includes seizures and status epilepticus. These acute toxic responses are associated with persistent neuroinflammation and spontaneous recurrent seizures (SRS), also known as acquired epilepsy. Blood-brain barrier (BBB) impairment has recently been proposed as a pathogenic mechanism linking acute OP intoxication to chronic adverse neurologic outcomes. In this review, we briefly describe the cellular and molecular components of the BBB, review evidence of altered BBB integrity following acute OP intoxication, and discuss potential mechanisms by which acute OP intoxication may promote BBB dysfunction. We highlight the complex interplay between neuroinflammation and BBB dysfunction that suggests a positive feedforward interaction. Lastly, we examine research from diverse models and disease states that suggest mechanisms by which loss of BBB integrity may contribute to epileptogenic processes. Collectively, the literature identifies BBB impairment as a convergent mechanism of neurologic disease and justifies further mechanistic research into how acute OP intoxication causes BBB impairment and its role in the pathogenesis of SRS and potentially other long-term neurologic sequelae. Such research is critical for evaluating BBB stabilization as a neuroprotective strategy for mitigating OP-induced epilepsy and possibly seizure disorders of other etiologies. SIGNIFICANCE STATEMENT: Clinical and preclinical studies support a link between blood-brain barrier (BBB) dysfunction and epileptogenesis; however, a causal relationship has been difficult to prove. Mechanistic studies to delineate relationships between BBB dysfunction and epilepsy may provide novel insights into BBB stabilization as a neuroprotective strategy for mitigating epilepsy resulting from acute organophosphate (OP) intoxication and non-OP causes and potentially other adverse neurological conditions associated with acute OP intoxication, such as cognitive impairment.
Topics: Rats; Animals; Humans; Blood-Brain Barrier; Brain; Neuroinflammatory Diseases; Organophosphates; Rats, Sprague-Dawley; Epilepsy; Organophosphate Poisoning; Acute Disease
PubMed: 37827702
DOI: 10.1124/jpet.123.001836 -
BMC Infectious Diseases Feb 2024The Food and Drug Administration (FDA) has licensed many antiretroviral medications to treat human immunodeficiency virus type 1 (HIV-1), however, treatment options for... (Review)
Review
The Food and Drug Administration (FDA) has licensed many antiretroviral medications to treat human immunodeficiency virus type 1 (HIV-1), however, treatment options for people with multi-drug resistant HIV remain limited. Medication resistance, undesirable effects, prior tolerance, and previous interlacement incapacity to deliver new drug classes all lead to the requirement for new medication classes and drug combination therapy. Fostemsavir (FTR) is a new CD-4 attachment inhibitor medicine that was recently authorized by the United States FDA to treat HIV-1. In individuals with multidrug-resistant (MDR) HIV-1, FTR is well tolerated and virologically active. According to recent investigations, drug combination therapy can positively affect MDR-HIV. The mechanism of action, resistance, interaction, pharmacokinetics, pharmacodynamics, and safety of FTR has been highlighted in this review.
Topics: United States; Humans; HIV Infections; HIV-1; Anti-Retroviral Agents; Drug Combinations; Anti-HIV Agents; Organophosphates; Piperazines
PubMed: 38395761
DOI: 10.1186/s12879-024-09122-5 -
Anais Da Academia Brasileira de Ciencias 2023Although it is known that organophosphate insecticides are harmfull to aquatic ecosystems, oxidative damages caused by Dimethoate and Chlorpyrifos are not studied on...
Although it is known that organophosphate insecticides are harmfull to aquatic ecosystems, oxidative damages caused by Dimethoate and Chlorpyrifos are not studied on Arthrospira platensis Gomont. In this study, various Chlorpyrifos (0-150 µg mL-1) and Dimethoate (0-250 µg mL-1) concentrations were added to the culture medium in laboratory to evaulate growth rate, chlorophyll-a content and antioxidant parameters of A. platensis. Optical Density (OD560) and chlorophyll-a decreased compared to the control for seven days in both pesticide applications. Superoxide dismutase (SOD) activity increased at 50 µg mL-1 Chlorpyrifos concentration but it decreased at all concentrations. Although Ascorbate peroxidase (APX) and glutathione reductase (GR) activities increased with Chlorpyrifos application, they did not change with Dimethoate application. Malondialdehyde (MDA) amount decreased at 150 µg mL-1 Chlorpyrifos concentration but it increased in Dimethoate application. The H2O2 content were increased in both applications. Proline decreased in 50 and 75 µg mL-1 Chlorpyrifos concentrations and increased at 150 µg mL-1 concentration, while it increased at 25 µg mL-1 Dimethoate concentration. The results were tested at 0.05 significance level. These pesticides inhibit A. platensis growth and chlorophyll-a production and cause oxidative stress. The excessive use may affect the phytoplankton and have negative consequences in the aquatic ecosystem.
Topics: Insecticides; Chlorpyrifos; Dimethoate; Ecosystem; Hydrogen Peroxide; Oxidative Stress; Pesticides; Antioxidants; Chlorophyll; Chlorophyll A; Organophosphorus Compounds
PubMed: 37729300
DOI: 10.1590/0001-3765202320200463 -
Reviews on Environmental Health Dec 2023Autism spectrum disorder (ASD) increased dramatically over the past 25 years because of genetic and environmental factors. This systematic review (SR) aimed to... (Review)
Review
Autism spectrum disorder (ASD) increased dramatically over the past 25 years because of genetic and environmental factors. This systematic review (SR) aimed to determine the association between maternal exposure during pregnancy to environmental pesticides and other associations with the risk of ASD progression in children. PubMed (MEDLINE), Scopus (Elsevier) and the Institute for Scientific Information (ISI) Web of Science were searched using appropriate keywords up to March 2021. Twenty-four studies met the inclusion/exclusion criteria and were selected. Most studies reported that ASD increases the risk of offspring after prenatal exposure to environmental pesticides in pregnant mother's residences, against offspring of women from the same region without this exposure. The main potential mechanisms inducing ASD progressions are ROS and prostaglandin E2 synthesis, AChE inhibition, voltage-gated sodium channel disruption, and GABA inhibition. According to the included studies, the highest rates of ASD diagnosis increased relative to organophosphates, and the application of the most common pesticides near residences might enhance the prevalence of ASD.
Topics: Pregnancy; Humans; Child; Female; Maternal Exposure; Autism Spectrum Disorder; Pesticides; Prenatal Exposure Delayed Effects; Organophosphates
PubMed: 36126654
DOI: 10.1515/reveh-2022-0092 -
Toxicological Sciences : An Official... Aug 2023Toxicogenomics is a critical area of inquiry for hazard identification and to identify both mechanisms of action and potential markers of exposure to toxic compounds....
Toxicogenomics is a critical area of inquiry for hazard identification and to identify both mechanisms of action and potential markers of exposure to toxic compounds. However, data generated by these experiments are highly dimensional and present challenges to standard statistical approaches, requiring strict correction for multiple comparisons. This stringency often fails to detect meaningful changes to low expression genes and/or eliminate genes with small but consistent changes particularly in tissues where slight changes in expression can have important functional differences, such as brain. Machine learning offers an alternative analytical approach for "omics" data that effectively sidesteps the challenges of analyzing highly dimensional data. Using 3 rat RNA transcriptome sets, we utilized an ensemble machine learning approach to predict developmental exposure to a mixture of organophosphate esters (OPEs) in brain (newborn cortex and day 10 hippocampus) and late gestation placenta of male and female rats, and identified genes that informed predictor performance. OPE exposure had sex specific effects on hippocampal transcriptome, and significantly impacted genes associated with mitochondrial transcriptional regulation and cation transport in females, including voltage-gated potassium and calcium channels and subunits. To establish if this holds for other tissues, RNAseq data from cortex and placenta, both previously published and analyzed via a more traditional pipeline, were reanalyzed with the ensemble machine learning methodology. Significant enrichment for pathways of oxidative phosphorylation and electron transport chain was found, suggesting a transcriptomic signature of OPE exposure impacting mitochondrial metabolism across tissue types and developmental epoch. Here we show how machine learning can complement more traditional analytical approaches to identify vulnerable "signature" pathways disrupted by chemical exposures and biomarkers of exposure.
Topics: Male; Pregnancy; Female; Animals; Rats; Transcriptome; Flame Retardants; Plasticizers; Placenta; Organophosphates; Brain; Esters
PubMed: 37399109
DOI: 10.1093/toxsci/kfad062 -
Journal of Environmental Science and... 2024Exposure to glyphosate produces various toxic effects, due to this, different methods have been evaluated for its elimination. The objective of this work was to...
Exposure to glyphosate produces various toxic effects, due to this, different methods have been evaluated for its elimination. The objective of this work was to formulate chitosan-based adsorbents and evaluate their efficiency in the removal of glyphosate . Four films were made by varying the weight ratio of silica/chitosan particles, and four sponges were made by varying the chitosan/chitosan ratio in a reticulated manner. Both adsorbents were characterized based on their porosity, water absorption, glyphosate removal, and reusability. It was found that increasing the porosity in both films and sponges resulted in an increase in the adsorption efficiency of glyphosate. The adsorption process exhibited a better fit in both adsorbents to the pseudo-second-order model. The adsorption of glyphosate to the films fit better with the Langmuir model, demonstrating that the process occurs in the form of a monolayer. In the case of sponges, the adsorption of glyphosate fit better with the Freundlich model, indicating that the process takes place in a multilayer form. Finally, when the reusability was evaluated, the adsorbents showed a loss of effectiveness. However, they still proved to be an efficient alternative for the removal of glyphosate in water, providing a cost-effective and environmentally friendly solution.
Topics: Glyphosate; Chitosan; Adsorption; Water; Kinetics; Water Pollutants, Chemical; Hydrogen-Ion Concentration; Water Purification
PubMed: 38099739
DOI: 10.1080/03601234.2023.2291980 -
Environmental Pollution (Barking, Essex... Feb 2024Organophosphate esters (OPEs) are increasingly considered neurotoxicants which may impact gross and fine motor development. We evaluated associations between prenatal...
Organophosphate esters (OPEs) are increasingly considered neurotoxicants which may impact gross and fine motor development. We evaluated associations between prenatal OPE exposures and infant motor development. Third trimester urinary concentrations of nine OPE metabolites were measured in 329 mother-infant dyads participating in the Maternal And Developmental Risks from Environmental and Social Stressors (MADRES) cohort. Child gross and fine motor development at 6, 9, 12, and 18-months were assessed with the Ages and Stages Questionnaire-3 (ASQ-3) and operationalized in models using dichotomous instrument-specific cutoffs for typical motor development. Five OPE metabolites with >60% detection were specific-gravity-adjusted, natural log-transformed, and modeled continuously, while four metabolites with <60% detection were modeled dichotomously (detected/not-detected). We fit mixed effects logistic regression between OPE metabolites and fine/gross motor development and assessed sex-specific effects using a statistical interaction term and sex-stratified models. Among children, 31% and 23% had gross and fine motor scores, respectively, below the ASQ-3 at-risk cutoffs at least once across infancy. A doubling in prenatal diphenyl phosphate (DPHP) exposure was associated with 26% increased odds of potential fine motor delays (OR = 1.26, 95% CI: 1.02, 1.57, p = 0.04). We also observed significant interactions by infant sex for associations of detected dipropyl phosphate (DPRP) with gross motor development (p = 0.048) and detected bis(1-chloro-2-propyl) phosphate (BCIPP) with fine motor development (p = 0.02). Females had greater odds of potential motor delays for both detected DPRP (females vs males OR (95% CI) = 1.48 (0.71, 3.09), p = 0.30 vs 0.27 (0.06, 1.29), p = 0.10) and detected BCIPP (females vs males OR (95% CI) = 2.72 (1.27, 5.85), p = 0.01 vs 0.76 (0.31, 1.90), p = 0.56). There were no other significant associations between other metabolites and motor development, despite similar patterns. We found evidence of adverse effects of prenatal OPE exposures on infant motor development with greater adverse effects among female infants with some OPE metabolites.
Topics: Male; Child; Infant; Pregnancy; Humans; Female; Prenatal Exposure Delayed Effects; Esters; Organophosphates; Phosphates; Flame Retardants
PubMed: 38092343
DOI: 10.1016/j.envpol.2023.123131 -
Journal of Hazardous Materials May 2024Evidence on the effects of internal chemical mixture exposures on biological age is limited. It also remains unclear whether hormone homeostasis and lifestyle factors...
Evidence on the effects of internal chemical mixture exposures on biological age is limited. It also remains unclear whether hormone homeostasis and lifestyle factors can modify such a relationship. Based on the Biomarkers for Air Pollutants Exposure (BAPE) study, which involved healthy older adults aged 60-69 years in China, we found that chemical mixture exposures, including metals, polycyclic aromatic hydrocarbons (PAHs), per- and polyfluoroalkyl substances (PFASs), phthalates (PAEs), and organophosphate esters (OPEs), were significantly associated with shortened DNAmTL and accelerated SkinBloodClock, in which PFASs and OPEs in blood were the primary contributors to DNAmTL, while metals and PAEs had relatively higher contributions in urine. Furthermore, lower levels of thyroxin appeared to exacerbate the adverse effects of environmental chemicals on epigenetic ageing but relatively higher levels of physical activity had the beneficial impact. These findings may have important implications for the development of healthy ageing strategy and aged care policy, particularly in light of the global acceleration of population ageing.
Topics: Polycyclic Aromatic Hydrocarbons; Thyroid Hormones; Biomarkers; Organophosphates; Exercise; Epigenesis, Genetic; Fluorocarbons; Environmental Pollutants
PubMed: 38492399
DOI: 10.1016/j.jhazmat.2024.134009 -
Chemosphere Dec 2023In recent years, the indoor exposure of organophosphate esters (OPEs) and novel brominated flame retardants (NBFRs) has received widespread attention worldwide. Using... (Review)
Review
Organophosphate esters (OPEs) and novel brominated flame retardants (NBFRs) in indoor dust: A systematic review on concentration, spatial distribution, sources, and human exposure.
In recent years, the indoor exposure of organophosphate esters (OPEs) and novel brominated flame retardants (NBFRs) has received widespread attention worldwide. Using published data on 6 OPEs in 23 countries (n = 1437) and 2 NBFRs in 18 countries (n = 826) in indoor dust, this study systematically reviewed the concentrations, spatial distribution, sources and exposure risk of 8 flame retardants (FRs) worldwide. Tris(chloroisopropyl)phosphate (TCIPP) is the predominant FR with a median concentration of 1050 ng g ΣCl-OPEs are significantly higher than Σnon-Cl-OPEs (p < 0.05). ΣOPEs in indoor dust from industrially-developed countries are higher than those from the countries lacking industrial development. Household appliances, electronics and plastic products are the main sources of non-Cl-OPEs and NBFRs, while interior decorations and materials contribute abundant Cl-OPEs in indoor dust. The mean hazard index (HI) of TCIPP for children is greater than 1, possibly posing non-cancer risk for children in some countries. The median ILCRs for 3 carcinogenic OPEs are all less than 10, suggesting no cancer risk induced by these compounds for both adults and children. This review helps to understand the composition, spatial pattern and human exposure risk of OPEs and NBFRs in indoor dust worldwide.
Topics: Child; Adult; Humans; Environmental Monitoring; Flame Retardants; Dust; Air Pollution, Indoor; Organophosphates; Esters; Environmental Exposure
PubMed: 37898464
DOI: 10.1016/j.chemosphere.2023.140560 -
Environmental Science & Technology Aug 2023Plastic recycling and reprocessing activities may release organophosphate ester (OPE) flame retardants and plasticizers into the surrounding environment. However, the...
Nontarget Identification of Novel Organophosphorus Flame Retardants and Plasticizers in Rainfall Runoffs and Agricultural Soils around a Plastic Recycling Industrial Park.
Plastic recycling and reprocessing activities may release organophosphate ester (OPE) flame retardants and plasticizers into the surrounding environment. However, the relevant contamination profiles and impacts remain not well studied. This study investigated the occurrence of 28 OPEs and their metabolites (mOPEs) in rainfall runoffs and agricultural soils around one of the largest plastic recycling industrial parks in North China and identified novel organophosphorus compounds (NOPs) using high-resolution mass spectrometry-based nontarget analysis. Twenty and twenty-seven OPEs were detected in runoff water and soil samples, with total concentrations of 86.0-2491 ng/L and 2.53-199 ng/g dw, respectively. Thirteen NOPs were identified, of which eight were reported in the environment for the first time, including a chlorine-containing OPE, an organophosphorus heterocycle, a phosphite, three novel OPE metabolites, and two oligomers. Triphenylphosphine oxide and diphenylphosphinic acid occurred ubiquitously in runoffs and soils, with concentrations up to 390 ng/L and 40.2 ng/g dw, respectively. The downwind areas of the industrial park showed elevated levels of OPEs and NOPs. The contribution of hydroxylated mOPEs was higher in soils than in runoffs. These findings suggest that plastic recycling and reprocessing activities are significant sources of OPEs and NOPs and that biotransformation may further increase the ecological and human exposure risk.
Topics: Humans; Plasticizers; Plastics; Organophosphorus Compounds; Flame Retardants; Soil; Organophosphates; China; Esters; Environmental Monitoring
PubMed: 37579047
DOI: 10.1021/acs.est.3c02156