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1.
Food Chem ; 368: 130835, 2022 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-34416487

RESUMO

A novel deep eutectic solvents (DES) was successfully applied as an emulsifier in vortex assisted liquid-liquid microextraction (VALLME) coupled with gas chromatography-mass spectrometry for the determination of organophosphorus pesticides in honey and fruit samples. Based on the result of toxicity study, DES provides new opportunities for the safe delivery and application. The predominant parameters affecting extraction efficiency were thoroughly optimized and studied in detail. Under optimum parameters, the calibration curve was determined in the concentration range of 0.1 to 200 µgL-1 with excellent determination coefficients values of 0.9989 to 0.9999. Limit of detection and limit of quantification were found to be 0.01 - 0.09 µgL-1 and 0.03 - 0.2 µgL-1, respectively. Application of the developed method to honey and fruit samples gave acceptable recovery values 83 - 109% with relative standard deviation below than 9.5%. The suggested approach has also proven to be simple, cost-effective, rapid, and non-toxic in nature.


Assuntos
Mel , Microextração em Fase Líquida , Praguicidas , Frutas/química , Mel/análise , Limite de Detecção , Compostos Organofosforados/toxicidade , Praguicidas/análise , Praguicidas/toxicidade , Solventes
2.
Sud Med Ekspert ; 64(5): 32-35, 2021.
Artigo em Russo | MEDLINE | ID: mdl-34644031

RESUMO

Objective - to identify the morphological equivalents of the cardiotoxic action of organophosphate poisoning. It was studied 110 fatal organophosphate poisonings in toxicogenic and somatogenic stages. The study of the heart was a comprehensive in term of clinical, biochemical, histological, micromorphometric, histochemical and histoenzymological approaches. We have identified a complex of deep metabolic disorders and necrobiotic changes in the heart muscle and the level of cholinesterase activity inhibition in the cholinergic structures of the heart in the toxicogenic and somatogenic stages of fatal organophosphate poisoning.


Assuntos
Intoxicação por Organofosfatos , Compostos Organofosforados , Acetilcolinesterase , Humanos , Compostos Organofosforados/toxicidade
3.
Anal Methods ; 13(38): 4390-4428, 2021 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-34486591

RESUMO

Organophosphorus pesticides (OPPs) are generally utilized for the protection of crops from pests. Because the use of OPPs in various agricultural operations has expanded dramatically, precise monitoring of their concentration levels has become the critical issue, which will help in the protection of ecological systems and food supply. However, the World Health Organization (WHO) has classified them as extremely dangerous chemical compounds. Taking their immense use and toxicity into consideration, the development of easy, rapid and highly sensitive techniques is necessary. Despite the fact that there are numerous conventional ways for detecting OPPs, the development of portable sensors is required to make routine analysis considerably more convenient. Some of these advanced techniques include colorimetric sensors, fluorescence sensors, molecular imprinted polymer-based sensors, and surface plasmon resonance-based sensors. This review article specifically focuses on the colorimetric, fluorescence and electrochemical sensors. In this article, the sensing strategies of these developed sensors, analytical conditions and their respective limit of detection are compiled.


Assuntos
Inseticidas , Praguicidas , Colorimetria , Organofosfatos/toxicidade , Compostos Organofosforados/toxicidade , Praguicidas/análise
4.
Biochemistry ; 60(38): 2875-2887, 2021 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-34494832

RESUMO

The G-type nerve agents, sarin (GB), soman (GD), and cyclosarin (GF), are among the most toxic compounds known. Much progress has been made in evolving the enzyme phosphotriesterase (PTE) from Pseudomonas diminuta for the decontamination of the G-agents; however, the extreme toxicity of the G-agents makes the use of substrate analogues necessary. Typical analogues utilize a chromogenic leaving group to facilitate high-throughput screening, and substitution of an O-methyl for the P-methyl group found in the G-agents, in an effort to reduce toxicity. Till date, there has been no systematic evaluation of the effects of these substitutions on catalytic activity, and the presumed reduction in toxicity has not been tested. A series of 21 G-agent analogues, including all combinations of O-methyl, p-nitrophenyl, and thiophosphate substitutions, have been synthesized and evaluated for their ability to unveil the stereoselectivity and catalytic activity of PTE variants against the authentic G-type nerve agents. The potential toxicity of these analogues was evaluated by measuring the rate of inactivation of acetylcholinesterase (AChE). All of the substitutions reduced inactivation of AChE by more than 100-fold, with the most effective being the thiophosphate analogues, which reduced the rate of inactivation by about 4-5 orders of magnitude. The analogues were found to reliably predict changes in catalytic activity and stereoselectivity of the PTE variants and led to the identification of the BHR-30 variant, which has no apparent stereoselectivity against GD and a kcat/Km of 1.4 × 106, making it the most efficient enzyme for GD decontamination reported till date.


Assuntos
Compostos Organofosforados/toxicidade , Sarina/análogos & derivados , Soman/análogos & derivados , Acetilcolinesterase/química , Catálise , Substâncias para a Guerra Química/química , Hidrólise , Agentes Neurotóxicos , Organofosfatos/química , Compostos Organofosforados/química , Compostos Organotiofosforados/química , Hidrolases de Triester Fosfórico/química , Sarina/química , Sarina/toxicidade , Soman/química , Soman/toxicidade
5.
Chem Biol Interact ; 346: 109578, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34265256

RESUMO

Current organophosphate (OP) toxicity research now considers potential non-cholinergic mechanisms for these compounds, since the inhibition of acetylcholinesterase (AChE) cannot completely explain all the adverse biological effects of OP. Thanks to the development of new strategies for OP detection, some potential molecular targets have been identified. Among these molecules are several cytoskeletal proteins, including actin, tubulin, intermediate filament proteins, and associated proteins, such as motor proteins, microtubule-associated proteins (MAPs), and cofilin. in vitro, ex vivo, and some in vivo reports have identified alterations in the cytoskeleton following OP exposure, including cell morphology defects, cells detachments, intracellular transport disruption, aberrant mitotic spindle formation, modification of cell motility, and reduced phagocytic capability, which implicate the cytoskeleton in OP toxicity. Here, we reviewed the evidence indicating the cytoskeletal targets of OP compounds, including their strategies, the potential effects of their alterations, and their possible participation in neurotoxicity, embryonic development, cell division, and immunotoxicity related to OP compounds exposure.


Assuntos
Citoesqueleto/metabolismo , Compostos Organofosforados/metabolismo , Actinas/metabolismo , Animais , Carcinogênese , Divisão Celular/efeitos dos fármacos , Desenvolvimento Embrionário/efeitos dos fármacos , Humanos , Proteínas Associadas aos Microtúbulos/metabolismo , Compostos Organofosforados/química , Compostos Organofosforados/toxicidade , Tubulina (Proteína)/metabolismo
6.
Environ Res ; 200: 111368, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34081974

RESUMO

Organophosphorus insecticides (OPIs) have low persistence and are easily biodegradable in nature. The United States and India are the major countries producing OPIs of about 25% and 17% of the world, respectively. OPIs commonly used for agricultural practices occupy a major share in the global market, which leads to the increasing contamination of OPIs residues in various food chains. To overcome this issue, an enzymatic degradation method has been approved by several environmental toxic, and controlling agencies, including United States Environmental Protection Agency (USEPA). Different catalytic enzymes have been isolated and identified from various microbial sources to neutralize the toxic pesticides and/or insecticides. In this review, we have gathered information on OPIs biotransformation and their residual toxicity in the environment. Particularly, it focuses on OPIs degrading enzymes such as chlorpyrifos hydrolase, diisopropylfluorophosphatase, organophosphate acid anhydrolase, organophosphate hydrolases, and phosphotriesterases like lactonasesspecific activity either P-O link group type or P-S link group of pesticides. To summarize, the catalytic degradation of organophosphorus insecticides is not only profitable but also environmentally friendly. Hence, the enzymatic catalyst is an ultimate and super bio-weapon to mitigate or decontaminate various OPIs residues in both terrestrial and aqueous environments.


Assuntos
Clorpirifos , Inseticidas , Praguicidas , Biodegradação Ambiental , Biotransformação , Compostos Organofosforados/toxicidade
7.
Int J Mol Sci ; 22(10)2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-34065337

RESUMO

Organophosphate flame retardants (OPFRs) are substances added to plastics, textiles, and furniture, and are used as alternatives to brominated flame retardants. As the use of OPFRs increases in the manufacturing industry, the concentration in the aquatic environment is also increasing. In this study, OPFRs introduced into a wastewater treatment plant (WWTP) were identified, and the toxicity of biotransformation molecules generated by the biological reaction was predicted. Tris(2-butoxyethyl) phosphate, tris(2-butoxyethyl) phosphate, and triphenyl phosphate were selected as research analytes. Chemicals were analyzed using high-resolution mass spectrometry, and toxicity was predicted according to the structure. As a result, tris(1-chloro-2-propyl) phosphate showed the highest concentration, and the removal rate of OPFRs in the WWTP was 0-57%. A total of 15 biotransformation products were produced by microorganisms in the WWTP. Most of the biotransformation products were predicted to be less toxic than the parent compound, but some were highly toxic. These biotransformation products, as well as OPFRs, could flow into the water from the WWTP and affect the aquatic ecosystem.


Assuntos
Biotransformação/fisiologia , Retardadores de Chama/toxicidade , Organofosfatos/química , Organofosfatos/toxicidade , Águas Residuárias/análise , Águas Residuárias/química , Ecossistema , Espectrometria de Massas/métodos , Compostos Organofosforados/química , Compostos Organofosforados/toxicidade , Purificação da Água/métodos
8.
Ecotoxicol Environ Saf ; 220: 112361, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34052757

RESUMO

Exposure to ethephon (ETH), a plant growth regulator commonly used for several purposes, can potentially decrease sperm numbers and viability. Occasional findings regarding ETH effects on female reproduction during early pregnancy have also been reported. During early pregnancy, endometrial decidualization is a critical event for embryo implantation and pregnancy maintenance. Thus, we aimed to explore the effect and mechanism of ETH on endometrial decidualization both in vivo and in vitro. Mice were gavaged with 0 and 285 mg/kg b.w. ETH from gestational days (GD)1 until sacrifice, whereas pseudopregnant mice from pseudopregnant day 1 (PPD-1) until PPD-8. Primary mouse endometrial stromal cells (mESCs) received 640 ug/ml ETH and added E2 and P4 to induce decidualization. Results indicated female albino CD1 mice exposed to high dose of ETH (285 mg/kg b.w.) by oral gavage, the number of embryo implantation sites on GD6 and GD8 were significantly decreased, the levels of serum E2 and P4 on GD8 were significantly decreased. Compared with the control group, the decidualization response artificially induced by corn oil in pseudopregnant mice and by E2 and P4 in primary mouse endometrial stromal cells (mESCs) was weakened in the high dose of ETH treated group. The high dose, 285 mg/kg b.w ETH treated group altered the expression of endometrial decidual markers on GD6 and GD8. The triglyceride and fatty acid metabolism-related genes were significantly increased after female albino CD1 mice exposed to high does, 285 mg/kg b.w ETH on GD6 and GD8. GPR120 was substantially reduced after ETH treatment. When overexpression of GPR120, the compromised decidualization induced by ETH treatment was rescued. Furthermore, molecular docking presented Thr234 and His251 of GPR120 as preferred binding sites for ETH. Mutation of these two sites rescued the compromised decidualization induced by ETH. In conclusion, we demonstrated that ETH exposure could impair decidualization during early pregnancy. GPR120 expression and binding between GPR120 and ETH are crucial for impaired decidualization mediated via ETH.


Assuntos
Endométrio/efeitos dos fármacos , Compostos Organofosforados/toxicidade , Reguladores de Crescimento de Plantas/toxicidade , Receptores Acoplados a Proteínas G/metabolismo , Animais , Decídua/efeitos dos fármacos , Decídua/metabolismo , Decídua/patologia , Implantação do Embrião/efeitos dos fármacos , Endométrio/metabolismo , Endométrio/patologia , Feminino , Camundongos , Simulação de Acoplamento Molecular , Compostos Organofosforados/química , Reguladores de Crescimento de Plantas/química , Gravidez , Receptores Acoplados a Proteínas G/química , Células Estromais/efeitos dos fármacos , Células Estromais/metabolismo , Células Estromais/patologia
9.
Aquat Toxicol ; 236: 105871, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34058436

RESUMO

Plastic is a globally recognized superwaste that can affect human health and wildlife when it accumulates and is amplified in the food chain. Microplastics (plastic particles < 5 mm) and nanoplastics (plastic particles < 100 nm) can interact with organic pollutants already present in the aquatic environment, potentially acting as carriers for pollutants entering organisms and thus influencing the bioavailability and toxicity of those pollutants. In this study, we investigated the transfer kinetics and transgenerational effects of exposure to tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) and polystyrene nanoplastics (PS-NPs) in F1 offspring. At 90 days postfertilization, zebrafish (Danio rerio) strain AB was exposed to either TDCIPP (0, 0.47, 2.64, or 12.78 µg/L) or PS-NPs (10 mg/L) or their combination for 120 days. The results showed that TDCIPP and PS-NPs accumulated in the gut, gill, head, and liver of the zebrafish in a sex-dependent manner. The presence of PS-NPs promoted the bioaccumulation of TDCIPP in the adult fish and increased the parental transfer of TDCIPP to their offspring. We demonstrate that parental exposure to TDCIPP alone or in combination with PS-NPs induces thyroid disruption in adults, and then leads to thyroid endocrine disruption in their larval offspring. Reduced thyroxine (T4) and 3,5,3'-triiodothyronine (T3) levels contributed to the observed transgenerational thyroid dysfunction, which inhibited developmental growth and disturbed the transcription of genes and expression of proteins involved in the hypothalamic-pituitary-thyroid (HPT) axis in the F1 larvae. The increased transfer of TDCIPP to the offspring in the presence of PS-NPs also enhanced transgenerational thyroid endocrine disruption, demonstrated by a further reduction in T4 and the upregulation of thyroglobulin (tg), uridine diphosphate-glucuronosyltransferase (ugt1ab), thyroid-stimulating hormone (tshß), and thyroid hormone receptor (trα) expression in the F1 larvae compared with the effects of parental TDCIPP exposure alone. Overall, our results indicate that the presence of PS-NPs modifies the bioavailability of TDCIPP and aggravates transgenerational thyroid disruption in zebrafish.


Assuntos
Compostos Organofosforados/toxicidade , Poliestirenos/toxicidade , Glândula Tireoide/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Animais , Disruptores Endócrinos/toxicidade , Humanos , Larva/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fosfatos/metabolismo , Plásticos , Poliestirenos/metabolismo , Receptores dos Hormônios Tireóideos/metabolismo , Tri-Iodotironina/metabolismo , Peixe-Zebra/metabolismo
10.
Inorg Chem ; 60(14): 10249-10256, 2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34037384

RESUMO

Pesticides are chemicals widely used for agricultural industry, despite their negative impact on health and environment. Although various methods have been developed for pesticide degradation to remedy such adverse effects, conventional materials often take hours to days for complete decomposition and are difficult to recycle. Here, we demonstrate the rapid degradation of organophosphate pesticides with a Zr-based metal-organic framework (MOF), showing complete degradation within 15 min. MOFs with different active site structures (Zr node connectivity and geometry) were compared, and a porphyrin-based MOF with six-connected Zr nodes showed remarkable degradation efficiency with half-lives of a few minutes. Such a high efficiency was further confirmed in a simple flow system for several cycles. This study reveals that MOFs can be highly potent heterogeneous catalysts for organophosphate pesticide degradation, suggesting that coordination geometry of the Zr node significantly influences the catalytic activity.


Assuntos
Estruturas Metalorgânicas/química , Compostos Organofosforados/química , Compostos Organofosforados/toxicidade , Praguicidas/química , Praguicidas/toxicidade , Zircônio/química , Catálise , Cinética
11.
J Hazard Mater ; 417: 126024, 2021 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-33992014

RESUMO

The chiral pesticide enantiomers often show selective efficacy and non-target toxicity. In this study, the enantioselective degradation characteristics of the chiral organophosphorus insecticide isocarbophos (ICP) by Cupriavidus nantongensis X1T were investigated systematically. Strain X1T preferentially degraded the ICP R isomer (R-ICP) over the S isomer (S-ICP). The degradation rate constant of R-ICP was 42-fold greater than S-ICP, while the former is less bioactive against pest insects but more toxic to humans than the latter. The concentration ratio of S-ICP to R-ICP determines whether S-ICP can be degraded by strain X1T. S-ICP started to degrade only when the ratio (CS-ICP/CR-ICP) was greater than 62. Divalent metal cations could improve the degradation ability of strain X1T. The detected metabolites that were identified suggested a novel hydrolysis pathway, while the hydrolytic metabolites were less toxic to fish and green algae than those from P-O bond breakage. The crude enzyme degraded both R-ICP and S-ICP in a similar rate, indicating that enantioselective degradation was due to the transportation of strain X1T. The strain X1T also enantioselectively degraded the chiral organophosphorus insecticides isofenphos-methyl and profenofos. The enantioselective degradation characteristics of strain X1T make it suitable for remediation of chiral organophosphorus insecticide contaminated soil and water.


Assuntos
Inseticidas , Animais , Biodegradação Ambiental , Cupriavidus , Humanos , Inseticidas/toxicidade , Malation/análogos & derivados , Compostos Organofosforados/toxicidade , Estereoisomerismo
12.
Int J Mol Sci ; 22(6)2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33802843

RESUMO

Poisoning with organophosphorus compounds (OPCs) represents an ongoing threat to civilians and rescue personal. We have previously shown that oximes, when administered prophylactically before exposure to the OPC paraoxon, are able to protect from its toxic effects. In the present study, we have assessed to what degree experimental (K-27; K-48; K-53; K-74; K-75) or established oximes (pralidoxime, obidoxime), when given as pretreatment at an equitoxic dosage of 25% of LD01, are able to reduce mortality induced by the OPC azinphos-methyl. Their efficacy was compared with that of pyridostigmine, the only FDA-approved substance for such prophylaxis. Efficacy was quantified in rats by Cox analysis, calculating the relative risk of death (RR), with RR=1 for the reference group given only azinphos-methyl, but no prophylaxis. All tested compounds significantly (p ≤ 0.05) reduced azinphos-methyl-induced mortality. In addition, the efficacy of all tested experimental and established oximes except K-53 was significantly superior to the FDA-approved compound pyridostigmine. Best protection was observed for the oximes K-48 (RR = 0.20), K-27 (RR = 0.23), and obidoxime (RR = 0.21), which were significantly more efficacious than pralidoxime and pyridostigmine. The second-best group of prophylactic compounds consisted of K-74 (RR = 0.26), K-75 (RR = 0.35) and pralidoxime (RR = 0.37), which were significantly more efficacious than pyridostigmine. Pretreatment with K-53 (RR = 0.37) and pyridostigmine (RR = 0.52) was the least efficacious. Our present data, together with previous results on other OPCs, indicate that the experimental oximes K-27 and K-48 are very promising pretreatment compounds. When penetration into the brain is undesirable, obidoxime is the most efficacious prophylactic agent already approved for clinical use.


Assuntos
Azinfos-Metil/toxicidade , Oximas/farmacologia , Animais , Azinfos-Metil/química , Inibidores da Colinesterase/farmacologia , Concentração Inibidora 50 , Peso Molecular , Compostos Organofosforados/química , Compostos Organofosforados/toxicidade , Praguicidas/química , Praguicidas/toxicidade , Modelos de Riscos Proporcionais , Ratos Wistar , Risco , Análise de Sobrevida
13.
Toxicol Sci ; 183(2): 404-414, 2021 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-33720374

RESUMO

Inhibition kinetics assays were conducted with 16 commercial organophosphate (OP) pesticides or their metabolites on acetylcholinesterase (AChE) in erythrocyte "ghost" preparations from 18 individual humans (both sexes; adults, juveniles, and cord blood samples; mixed races/ethnicities) and pooled samples from adult rats (both sexes). A well-established spectrophotometric assay using acetylthiocholine as substrate and a chromogen was employed. The kinetic parameters bimolecular rate constant (ki), dissociation constant (KI), and phosphorylation constant (kp) were calculated for each compound. As expected, a wide range of potencies were displayed among the tested compounds. Statistical analysis of the resultant data indicated no differences in sex, age, or race/ethnicity among the human samples that are unexpected based on chance (4.2% statistically significant out of 48 parameters calculated) and no differences between the sexes in rats. The bimolecular rate constants for 10 of the compounds were not statistically different between rats and humans. The data indicate that, consistent with the high level of conservation of AChE among species and the fact that AChE at different locations within a species arises from the same gene, the inhibition kinetic parameters calculated from rat erythrocyte ghost preparations should be useful in estimating potencies of OP compounds on target AChE in humans. Additionally, the data indicate that differences in sensitivities among individual humans were not apparent.


Assuntos
Acetilcolinesterase , Praguicidas , Acetilcolinesterase/metabolismo , Animais , Inibidores da Colinesterase/toxicidade , Eritrócitos/metabolismo , Feminino , Humanos , Cinética , Masculino , Compostos Organofosforados/toxicidade , Praguicidas/toxicidade , Ratos
14.
Sensors (Basel) ; 21(5)2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33668135

RESUMO

This study aimed to determine the impact of tetrabutylphosphonium bromide [TBP][Br] on the soil environment through an experiment on loamy sand samples. The tested salt was added to soil samples at doses of 0 (control), 1, 10, 100, and 1000 mg kg-1 dry matter (DM). During the experiment, the activity of selected enzymes involved in carbon, phosphorus, and nitrogen cycles, characteristics of organic matter with Fourier-transform infrared (FT-IR) spectroscopy, and toxicity of soil samples in relation to Aliivibrio fischeri were determined at weekly intervals. The results showed that low doses of [TBP][Br] (1 and 10 mg kg-1 DM) did not have much influence on the analyzed parameters. However, the addition of higher doses of the salt into the soil samples (100 and 1000 mg kg-1 DM) resulted in a decrease in the activity of enzymes participating in the carbon and phosphorus cycle and affected the activation of those enzymes involved in the nitrogen cycle. This may be due to changes in aerobic conditions and in the qualitative and quantitative composition of soil microorganisms. It was also observed that the hydrophobicity of soil organic matter was increased. Moreover, the findings suggested that the soil samples containing the highest dose of [TBP][Br] (1000 mg kg-1 DM) can be characterized as acute environmental hazard based on their toxicity to Aliivibrio fischeri bacteria. The increased hydrophobicity and ecotoxicity of the soil samples exposed to the tested salt were also positively correlated with the activity of dehydrogenases, proteases, and nitrate reductase. Observed changes may indicate a disturbance of the soil ecochemical state caused by the presence of [TBP][Br].


Assuntos
Aliivibrio fischeri/efeitos dos fármacos , Aliivibrio fischeri/enzimologia , Compostos Organofosforados/toxicidade , Poluentes do Solo/toxicidade , Solo , Espectroscopia de Infravermelho com Transformada de Fourier
15.
Int J Mol Sci ; 22(4)2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33672330

RESUMO

Mushroom poisoning has always been a threat to human health. There are a large number of reports about ingestion of poisonous mushrooms every year around the world. It attracts the attention of researchers, especially in the aspects of toxin composition, toxic mechanism and toxin application in poisonous mushroom. Inocybe is a large genus of mushrooms and contains toxic substances including muscarine, psilocybin, psilocin, aeruginascin, lectins and baeocystin. In order to prevent and remedy mushroom poisoning, it is significant to clarify the toxic effects and mechanisms of these bioactive substances. In this review article, we summarize the chemistry, most known toxic effects and mechanisms of major toxic substances in Inocybe mushrooms, especially muscarine, psilocybin and psilocin. Their available toxicity data (different species, different administration routes) published formerly are also summarized. In addition, the treatment and medical application of these toxic substances in Inocybe mushrooms are also discussed. We hope that this review will help understanding of the chemistry and toxicology of Inocybe mushrooms as well as the potential clinical application of its bioactive substances to benefit human beings.


Assuntos
Agaricales/química , Intoxicação Alimentar por Cogumelos/etiologia , Intoxicação Alimentar por Cogumelos/terapia , Agaricales/metabolismo , Agaricales/fisiologia , Animais , Humanos , Lectinas/química , Lectinas/farmacologia , Muscarina/química , Muscarina/envenenamento , Muscarina/toxicidade , Compostos Organofosforados/química , Compostos Organofosforados/toxicidade , Psilocibina/análogos & derivados , Psilocibina/química , Psilocibina/envenenamento , Psilocibina/toxicidade , Triptaminas/química , Triptaminas/toxicidade
16.
Environ Pollut ; 274: 116541, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33529899

RESUMO

Organophosphorus flame retardants (OPFRs), a group of new emerging endocrine disruption chemicals, have been reported to cause metabolic disturbance. Currently, mitochondrial abnormality is a new paradigm for evaluating chemical-mediated metabolic disruption. However, a comprehensive correlation between these two aspects of OPFR remains elusive. In the work reported here, 3 markers for morphological abnormality, and 7 markers of mitochondrial dysfunction were detected after treatment with two aryl-OPFRs (TCP and TPhP) and three chlorinated-OPFRs (TDCPP, TCPP, and TCEP) on hepatocyte. The two aryl-OPFRs and TDCPP can cause intracellular lipid accumulation at non-cytotoxic concentrations (<10 µM), while the other two chlorinated-OPFRs only caused lipid deposition at 10 µM. Furthermore, at the tested concentrations, all of them reduced mitochondrial (mito)-network numbers, enlarged mito-area/cells, and skewed mitoATP/glycoATP. Excluding TCEP, the other four chemicals induced mito-ROS and depleted mitochondrial membrane potential (MMP). Notably, only TCP, TPhP and TDCPP impeded mitoATP generation rate and mito-respiratory rate. Based on potency estimates, the capacity for lipid accumulation was significantly correlated with mito-network numbers (R2 = 0.6481, p < 0.01), mitoATP/glycoATP (R2 = 0.5197, p < 0.01), mitoROS (R2 = 0.7197, p < 0.01), and MMP (R2 = 0.7715, p < 0.01). Remarkably, the mito-respiratory rate (R2 = 0.8753, p < 0.01) exhibited the highest correlation. Thus, the more potent lipid inducers TPhP, TCP and TDCPP could be identified. The results of this study demonstrate that aryl-OPFRs are more potent in metabolic disruption than other esters examined. Metabolic disruption should be examined further for chemicals that have the capacity to counteract the aforementioned functions of mitochondrial.


Assuntos
Retardadores de Chama , Retardadores de Chama/toxicidade , Hepatócitos , Mitocôndrias , Organofosfatos , Compostos Organofosforados/toxicidade
17.
Toxicology ; 453: 152725, 2021 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-33617914

RESUMO

Organophosphorus compounds (OP) causes prominent delayed neuropathy in vivo and cytotoxicity to neuronal cells in vitro. The primary target protein of OP's neurotoxicity is neuropathy target esterase (NTE), which can convert phosphatidylcholine (PC) to glycerophosphocholine (GPC). Recent studies reveal that autophagic cell death is important for the initiation and progression of OP-induced neurotoxicity both in vivo and in vitro. However, the mechanism of how OP induces autophagic cell death is unknown. Here it is found that GPC is an important organic osmolyte in the neuroblastoma cells, and treatment with tri-o-cresyl phosphate (TOCP), a representative OP, leads to the decrease of GPC and imbalance of extracellular and intracellular osmolality. Knockdown of GPC metabolizing enzyme glycerophosphodiester phosphodiesterase domain containing 5 (GDPD5) reverses TOCP-induced autophagic cell death, which further supports the notion that the reduced GPC level leads to the autophagic cell death. Furthermore, it is found that autophagic cell death is due to the induction of reactive oxygen species (ROS) and mitochondrial damage by imbalance of osmolality with TOCP treatment. In summary, this study reveals that TOCP treatment decreases GPC level and intracellular osmolality, which induces ROS and mitochondrial damage and leads to the cell death and neurite degradation by autophagy. This study lays the foundation for further investigations on the potential therapeutic approaches for OP neurotoxicity or NTE mutation-related neurological diseases.


Assuntos
Citotoxinas/toxicidade , Líquido Intracelular/efeitos dos fármacos , Líquido Intracelular/metabolismo , Neuroblastoma/metabolismo , Compostos Organofosforados/toxicidade , Autofagia/efeitos dos fármacos , Autofagia/fisiologia , Linhagem Celular Tumoral , Humanos , Concentração Osmolar
18.
J Hazard Mater ; 413: 125281, 2021 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-33582465

RESUMO

Increasing use of organophosphorus flame retardants (OPFRs) has aroused great concern to their uncertain environment risk, especially to human health risk. In our study, hepatotoxicity screening of six aryl-OPFRs, potential hepatotoxicity mechanism of 2-ethylhexyldiphenyl phosphate (EHDPP) using RNA-sequencing and its metabolites were investigated in human hepatocytes (L02). The toxicity results demonstrated that EHDPP should be prioritized for further research with the highest toxicity. Further RNA-seq results through GO and KEGG enrichment analysis indicated that exposure to 10 mg/L of EHDPP significantly affected energy homeostasis, endoplasmic reticulum (ER) stress, apoptosis, cell cycle, and inflammation response in cells. The top 12 hub genes were validated by RT-qPCR and conformed to be mainly related to glycolysis and ER stress, followed by cell cycle and inflammation response. Western blot, apoptosis detection, glycolysis stress test, and cell cycle analysis were further performed to verify the above main pathways. Additionally, it was found in the metabolism experiment that detoxification of EHDPP by phase I and phase II metabolism in cells wasn't significant until 48 h with a metabolic rate of 6.12%. EHDPP was stable and still dominated the induction of toxicity. Overall, this study provided valuable information regarding the toxicity and potential metabolism pathway of EHDPP.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Retardadores de Chama , Doença Hepática Induzida por Substâncias e Drogas/genética , Retardadores de Chama/toxicidade , Hepatócitos , Humanos , Organofosfatos/toxicidade , Compostos Organofosforados/toxicidade , Fosfatos , Transcriptoma
19.
J Exp Zool A Ecol Integr Physiol ; 335(3): 339-347, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33503327

RESUMO

Tris(1-chloro-2-propyl)phosphate (TCPP) is the most common chlorinated organophosphorus flame retardant in seawater. Due to its chemical features and abundance, TCPP has been classified as a high hazard, and restrictions of use have been set in multiple countries. Despite TCPP being highly present in the marine environment, only a few studies have explored the TCPP impact on the development of marine invertebrates. Ascidians are important invertebrate members of benthic marine communities and reliable model systems for ecotoxicological research. The aim of this study was to assess the adverse effects of TCPP exposure on the embryogenesis of the ascidian Ciona intestinalis. Our results showed that this pollutant affected both muscles and nervous system development. Malformations appeared similar to those reported in other animal models for other flame retardants, suggesting that these molecules could share a common mechanism of action and induce a mixture effect when simultaneously present in the aquatic environment even at sub-teratogenic concentrations.


Assuntos
Ciona intestinalis/efeitos dos fármacos , Ciona intestinalis/embriologia , Embrião não Mamífero/efeitos dos fármacos , Retardadores de Chama/toxicidade , Compostos Organofosforados/toxicidade , Animais
20.
J Hazard Mater ; 409: 124999, 2021 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-33454525

RESUMO

Organophosphorus flame retardants (OPFRs) have been implicated as neurotoxicants, but their potential neurotoxicity and mechanisms remain poorly understood. Herein, we investigated the neurotoxicity of selected OPFRs using zebrafish as a model organism. Environmentally relevant concentrations (3-1500 nM) of three classes of OPFRs (aryl-OPFRs, chlorinated-OPFRs, and alkyl-OPFRs) were tested in zebrafish larvae (2-144 h post-fertilisation) alongside the neurotoxic chemical chlorpyrifos (CPF) that inhibits acetylcholinesterase (AChE). Exposure to aryl-OPFRs and CPF inhibited AChE activities, while chlorinated- and alkyl-OPFRs did not inhibit these enzymes. Biolayer interferometry (BLI) was used to probe interactions between OPFRs and AChE. The association and dissociation response curves showed that, like CPF, all three selected aryl-OPFRs, triphenyl phosphate (TPHP), tricresyl phosphate (TCP) and cresyl diphenyl phosphate (CDP), bound directly to AChE. The affinity constant (KD) for TPHP, TCP, CDP and CPF was 2.18 × 10-4, 5.47 × 10-5, 1.05 × 10-4 and 1.70 × 10-5 M, respectively. In addition, molecular docking revealed that TPHP, TCP, CDP and CPF bound to AChE with glide scores of - 7.8, - 8.3, - 8.1 and - 7.3, respectively. Furthermore, the calculated binding affinity between OPFRs and AChE correlated well with the KD values measured by BLI. The present study revealed that aryl-OPFRs can act as potent AChE inhibitors, and may therefore present a significant ecological risk to aquatic organisms.


Assuntos
Retardadores de Chama , Acetilcolinesterase , Animais , Retardadores de Chama/toxicidade , Interferometria , Simulação de Acoplamento Molecular , Organofosfatos , Compostos Organofosforados/toxicidade , Peixe-Zebra
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