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1.
Ecotoxicol Environ Saf ; 203: 111046, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32888614

RESUMO

Agricultural pesticides serve as effective controls of unwanted weeds and pests. However, these same chemicals can exert toxic effects in non-target organisms. To determine chemical modes of action, the toxicity ratio (TR) and critical body residues (CBRs) of 57 pesticides were calculated for Daphnia magna. Results showed that the CBR values of inert compounds were close to a constant while the CBR values of pesticides varied over a wider range. Although herbicides are categorized as specifically-acting compounds to plants, herbicides did not exhibit excess toxicity to Daphnia magna and were categorized as inert compounds with an average logTR = 0.41, which was less than a threshold of one. Conversely, fungicides and insecticides exhibited strong potential for toxic effects to Daphnia magna with an average logTR >2. Many of these chemicals act via disruption of the nervous, respiratory, or reproductive system, with high ligand-receptor binding activity which leads to higher toxicity for Daphnia magna. Molecular docking using acetylcholinesterase revealed that fungicides and insecticides bind more easily with the biological macromolecule when compared with inert compounds. Quantitative structure-activity relationship (QSAR) analysis revealed that the toxicity of fungicides was mainly dependent upon the heat of formation and polar surface area, while the toxicity of insecticides was more related to hydrogen-bond properties. This comprehensive analysis reveals that there are specific differences in toxic mechanisms between fungicides and insecticides. These results are useful for determining relative risk associated with pesticide exposure to aquatic crustaceans, such as Daphnia magna.


Assuntos
Daphnia/efeitos dos fármacos , Modelos Biológicos , Praguicidas/química , Praguicidas/toxicidade , Poluentes Químicos da Água/química , Poluentes Químicos da Água/toxicidade , Acetilcolinesterase/metabolismo , Animais , Daphnia/metabolismo , Relação Dose-Resposta a Droga , Fungicidas Industriais/química , Fungicidas Industriais/toxicidade , Herbicidas/química , Herbicidas/toxicidade , Ligação de Hidrogênio , Inseticidas/química , Inseticidas/toxicidade , Simulação de Acoplamento Molecular , Resíduos de Praguicidas/metabolismo , Relação Quantitativa Estrutura-Atividade
2.
J Oleo Sci ; 69(8): 941-950, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32759552

RESUMO

This study reports the biological activity of essential oils from fertility tree and horseradish tree leaves, and the mechanisms by which these oils promote insecticidal activity using Drosophila melanogaster as a model organism. Adult D. melanogaster were exposed to these essential oils at a final concentration of 10 µL/g for 24 hours. The exposure of flies to the essential oil resulted in significant decrease in their survival and fecundity. In addition, the essential oils produced significant reduction in acetylcholinesterase activity and induced oxidative stress in the flies as evidenced by an increase in reactive oxygen species, thiol and thiobarbituric reactive substance levels, as well as catalase activity. The essential oils were also characterized by gas chromatography coupled with mass spectrometry. Constituents such as terpenoids, Bis (2-ethylhexyl) phthalate, benzeneacetaldehyde, phytol, octadecane, 9,12-octadecadienoic acid (Z,Z)- methyl ester, heneicosane, eicosane and others were characterized. Therefore, our results point out to the potential application of fertility tree and horseradish tree leaf essential oils as natural alternatives to synthetic insecticides in agricultural and pest control practices, especially against dipterans.


Assuntos
Acetilcolinesterase/metabolismo , Bignoniaceae/química , Drosophila melanogaster/efeitos dos fármacos , Drosophila melanogaster/metabolismo , Inseticidas , Moringa oleifera/química , Óleos Voláteis/isolamento & purificação , Óleos Voláteis/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Folhas de Planta/química , Animais , Relação Dose-Resposta a Droga , Óleos Voláteis/química , Ácidos Ftálicos/análise , Espécies Reativas de Oxigênio/metabolismo , Terpenos/análise , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Fatores de Tempo
3.
J Environ Sci Health B ; 55(9): 803-812, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32602772

RESUMO

Organophosphorus pesticides induce gender-specific developmental neurotoxicity after birth, especially in adolescents and adults. However, whether and when the selectivity occurs in fetus remains unclear. In this study, we analyzed chlorpyrifos (CPF)-induced neurotoxicity in the early fetal brains of male and female mice. The gestational dams were administered 0, 1, 3, and 5 mg/(kg.d) CPF during gestational days (GD)7-11, and brains from the fetuses were isolated and analyzed on GD12. Fetal gender was identified by PCR technique based on male-specific Sry gene and Myog control gene. The body weight and head weight, the activity of acetylcholinesterase (AChE), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), and the content of malondialdehyde (MDA), as well as the oxidative stress-related gene expression were examined. Our results showed that CPF pretreatment induced AChE inhibition in GD12 fetal brain. CPF treatment activated SOD and GPX but not CAT and MDA. For oxidative stress-related gene expression, CPF pretreatment increased mRNA expression of Sod1, Cat, Gpx1, and Gpx2 in the fetal brain on GD12. The statistical analysis did not show gender-selective CPF-induced toxicity. Moreover, our results showed that although the gestational exposure to CPF could elicit abnormalities in the early fetal brain, the toxicity observed was not gender-specific.


Assuntos
Encéfalo/efeitos dos fármacos , Encéfalo/embriologia , Clorpirifos/toxicidade , Inseticidas/toxicidade , Acetilcolinesterase/metabolismo , Animais , Peso Corporal/efeitos dos fármacos , Encéfalo/metabolismo , Catalase/genética , Catalase/metabolismo , Inibidores da Colinesterase/toxicidade , Feminino , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Masculino , Malondialdeído/metabolismo , Camundongos Endogâmicos ICR , Síndromes Neurotóxicas/etiologia , Tamanho do Órgão/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/genética , Fatores Sexuais , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Testes de Toxicidade/métodos
4.
Parasitol Res ; 119(9): 2783-2798, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32683559

RESUMO

Due to the increasing consumption of platinum (Pt), especially in automobile exhaust catalysts, environmental concentrations of Pt are of emerging concern worldwide. Limited information exists on environmental concentrations, particularly in Pt mining regions, while South Africa is the world's main supplier of Pt. Moreover, other metals are also released as by-products of Pt mining, which might also cause environmental concern. Certain fish parasite taxa have the ability to accumulate metals orders of magnitude higher than their hosts and can be used to reliably detect metals with naturally low abundance. Studies on Pt accumulation in parasite-host systems are limited. Therefore, the aims of the present study were (1) to determine the accumulation of a variety of metals (cadmium (Cd), chromium (Cr), copper (Cu), nickel (Ni), lead (Pb), platinum (Pt), and zinc (Zn)) in helminth fish parasites compared with their hosts from a reference site and an impoundment impacted by Pt mining activities; (2) to assess whether there is a difference between bioaccumulation of metals in infected and uninfected hosts, as well as between hosts with different infection intensities; and (3) to compare the biomarker responses (acetylcholine esterase activity (AChE), metallothionein content (MT), catalase activity (CAT), reduced glutathione content (GSH), malondialdehyde content (MDA), protein carbonyls induction (PC), superoxide dismutase activity (SOD), and cellular energy allocation (CEA)) between infected and uninfected hosts. The cestode Atractolytocestus huronensis accumulated significantly higher concentrations of Cr, Ni, and Pt than their host Cyprinus carpio, while the nematode Contracaecum sp. accumulated significantly higher concentrations of Pt and Zn than their host Clarias gariepinus. Infected fish showed lower metal concentrations compared to uninfected fish, while the parasites had no significant effects on their hosts' biomarker responses. The parasites demonstrated the bioavailability of metals derived from Pt mining activities and their ability to resist its toxic effects. Thus, these parasites are promising sensitive accumulation indicators for Cr, Ni, Pb, and Pt contaminations from Pt mining activities.


Assuntos
Bioacumulação/fisiologia , Cestoides/química , Metais Pesados/análise , Nematoides/química , Emissões de Veículos/análise , Poluentes Químicos da Água/análise , Acetilcolinesterase/metabolismo , Animais , Cádmio/análise , Cádmio/toxicidade , Carpas/parasitologia , Catalase/metabolismo , Peixes-Gato/parasitologia , Cobre/análise , Cobre/toxicidade , Ecossistema , Monitoramento Ambiental , Glutationa/análise , Malondialdeído/análise , Metalotioneína/análise , Metais Pesados/toxicidade , Parasitos , Platina/análise , Platina/toxicidade , África do Sul , Superóxido Dismutase/metabolismo , Emissões de Veículos/toxicidade , Poluentes Químicos da Água/toxicidade
5.
Environ Toxicol ; 35(10): 1091-1099, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32485069

RESUMO

Various pollutants co-exist in the aquatic environment such as carbamazepine (CBZ) and copper (Cu), which can cause complex effects on inhabiting organisms. The toxic impacts of the single substance have been studied extensively. However, the studies about their combined adverse impacts are not enough. In the present study, zebrafish were exposed to environmental relevant concentrations of CBZ (1, 10, and 100 µg/L), Cu (0.5, 5, and 10 µg/L) and the mixtures (1 µg/L CBZ + 0.5 µg/L Cu, 10 µg/L CBZ + 5 µg/L Cu, 100 µg/L CBZ + 10 µg/L Cu) for 45 days, the effects on nervous and antioxidant systems of zebrafish were investigated. The results demonstrated that, in comparison with single exposure group, the combined presence of CBZ and Cu exacerbated the effect of antioxidant system (the ability of inhibition of hydroxyl radicals (IHR), superoxide dismutase (SOD), catalase (CAT) and glutathione S-transferase (GST)) but not nervous system (Acetylcholinesterase [AChE]). The qPCR results supported the changes of corresponding enzymes activities. Hepatic histopathological analysis verified the results of biomarkers. Our work illustrated that the toxicity of mixed pollutants is very complicated, which cannot simply be inferred from the toxicity of single pollutant, and calls for more co-exposure experiments to better understanding of the co-effects of pollutants on aquatic organisms.


Assuntos
Antioxidantes/metabolismo , Carbamazepina/toxicidade , Cobre/toxicidade , Sistema Nervoso/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/metabolismo , Acetilcolinesterase/genética , Acetilcolinesterase/metabolismo , Animais , Biomarcadores/metabolismo , Catalase/genética , Catalase/metabolismo , Relação Dose-Resposta a Droga , Regulação para Baixo , Sinergismo Farmacológico , Expressão Gênica/efeitos dos fármacos , Glutationa Transferase/genética , Glutationa Transferase/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Sistema Nervoso/enzimologia , Sistema Nervoso/metabolismo , Estresse Oxidativo/genética , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo
6.
Life Sci ; 256: 117892, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32502538

RESUMO

BACKGROUND: Organophosphorus pesticides exert their toxic effects mainly by the inhibition of acetylcholinesterase (AChE), which is related to emotional disorders, such as depression. Atropine-oximes therapy is commonly used; however, the efficacy of oximes in the reactivation of AChE has been inconsistent. The objective of this study was to investigate the possible neuroprotective effect of (3Z)-5-Chloro-3-(hydroxyimino)indolin-2-one (Cℓ-HIN), a compound that combines the isatin and oxime functional groups, in rats exposed to malathion. The effect of Cℓ-HIN on the AChE activity and the BDNF-Trkß pathway in the prefrontal cortex of malathion-exposed rats were tested. METHODS: Wistar male rats were co-treated with Cℓ-HIN [50 mg/kg (p.o.) (3 mL/kg)] and/or malathion [250 mg/kg (i.p.) (5 mL/kg)] and performed behavioral tests twelve hours after these exposures. RESULTS: The Cℓ-HIN reversed the increased immobility time in the forced swimming test and the decreased grooming time in the splash test induced by malathion, but any significant difference was observed in locomotion analysis. These results demonstrate the antidepressant-like effect of Cℓ-HIN. The cortical AChE activity was reactivated by Cℓ-HIN in rats exposed to malathion. Malathion induced an increase in Trkß and a decrease in BDNF levels in the prefrontal cortex of rats, which were avoided by Cℓ-HIN. CONCLUSION: These findings support the hypothesis that Cℓ-HIN is an AChE reactivator with antidepressant-like properties, which is related to the improvement of BDNF-Trkß signaling after acute exposure to malathion in rats. Thus, the results allow suggesting the potential use of Cℓ-HIN as an oxime-based therapy against the neurotoxic effects of malathion.


Assuntos
Acetilcolinesterase/metabolismo , Antidepressivos/farmacologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Indóis/farmacologia , Malation/toxicidade , Receptor trkB/metabolismo , Transdução de Sinais , Animais , Antidepressivos/administração & dosagem , Antidepressivos/química , Antidepressivos/uso terapêutico , Comportamento Animal/efeitos dos fármacos , Depressão/tratamento farmacológico , Indóis/administração & dosagem , Indóis/química , Indóis/uso terapêutico , Masculino , Atividade Motora/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos
7.
Chemosphere ; 259: 127419, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32593003

RESUMO

Carbofuran is one of the most toxic broad-spectrum and systemic N-methyl carbamate pesticide, which is extensively applied as insecticide, nematicide and acaricide for agricultural, domestic and industrial purposes. It is extremely lethal to mammals, birds, fish and wildlife due to its anticholinesterase activity, which inhibits acetyl-cholinesterase and butyrylcholinesterse activity. In humans, carbofuran is associated with endocrine disrupting activity, reproductive disorders, cytotoxic and genotoxic abnormalities. Therefore, cleanup of carbofuran-contaminated environments is of utmost concern and urgently needs an adequate, advanced and effective remedial technology. Microbial technology (bacterial, fugal and algal species) is a very potent, pragmatic and ecofriendly approach for the removal of carbofuran. Microbial enzymes and their catabolic genes exhibit an exceptional potential for bioremediation strategies. To understand the specific mechanism of carbofuran degradation and involvement of carbofuran hydrolase enzymes and genes, highly efficient genomic approaches are required to provide reliable information and unfold metabolic pathways. This review briefly discusses the carbofuran toxicity and its toxicological impact into the environment, in-depth understanding of carbofuran degradation mechanism with microbial strains, metabolic pathways, molecular mechanisms and genetic basis involved in degradation.


Assuntos
Biodegradação Ambiental , Carbofurano/toxicidade , Inibidores da Colinesterase/toxicidade , Poluentes Ambientais/toxicidade , Acetilcolinesterase/metabolismo , Animais , Carbamatos , Carbofurano/metabolismo , Inibidores da Colinesterase/metabolismo , Poluentes Ambientais/metabolismo , Humanos , Hidrolases , Inseticidas/metabolismo , Inseticidas/toxicidade , Redes e Vias Metabólicas
8.
Ecotoxicol Environ Saf ; 201: 110725, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32474209

RESUMO

Lincomycin hydrochloride is one of the commonly used drugs in clinic. However, it has many side effects on patients, and its mechanism is still poorly understood. In this study, 6 h post-fertilization (6 hpf) zebrafish embryos were exposed to several concentrations of lincomycin hydrochloride (15, 30, 60 µg/mL) for up to 24 or 96 hpf to detect their developmental toxicity and neurotoxicity, and to 6 days post-fertilization (6 dpf) to detect their behavioral toxicity. Our results showed that lincomycin hydrochloride could lead to embryonic head deformities (unclear ventricles, smaller ventricles, fewer new neurons). The studies showed that the frequency of spontaneous tail flick of zebrafish embryo increased at 24 hpf, and the lincomycin hydrochloride exposed zebrafish embryos showed increased heart rate, shorter body length, and yolk sac edema with severe pericardial edema at 96 hpf. The studies also showed that lincomycin hydrochloride increased oxidative stress level, Acetylcholinesterase (AChE) activity, ATPase activity and apoptosis in zebrafish larvae. In addition, the swimming behavior of zebrafish larvae decreased with the increase of lincomycin hydrochloride concentration, but the angular velocity and meandering degree increased, which might be due to the decreased activity of AChE and ATPase, as well as the decreased expression of genes related to neurodevelopment and neurotransmitter system, leading to the change of their motor behaviors. In summary, we found that lincomycin hydrochloride induced developmental toxicity and neurotoxicity in zebrafish larvae, contributing to a more comprehensive evaluation of the safety of the drug.


Assuntos
Lincomicina/toxicidade , Síndromes Neurotóxicas/etiologia , Acetilcolinesterase/metabolismo , Adenosina Trifosfatases/metabolismo , Animais , Apoptose/efeitos dos fármacos , Desenvolvimento Embrionário/efeitos dos fármacos , Larva/efeitos dos fármacos , Larva/crescimento & desenvolvimento , Síndromes Neurotóxicas/congênito , Estresse Oxidativo/efeitos dos fármacos , Peixe-Zebra
9.
Life Sci ; 256: 117915, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32504752

RESUMO

AIMS: Autonomic dysfunction in arterial hypertension affects cardiorespiratory control and gastric motility and has been characterized by increased sympathetic and reduced parasympathetic activity. In the present work we investigated the effects of anticholinesterase drugs [donepezil (DON) or pyridostigmine (PYR)] on cardiovascular, autonomic, and gastric parameters in L-NAME-induced hypertensive rats. MATERIALS AND METHODS: Daily oral gavage of L-NAME (70 mg/kg/day) was performed over 14 days in male Wistar rats (180-220 g), whereas daily oral gavage of DON or PYR (1.6 and 22 mg/kg/day, respectively) started 2 days after the L-NAME treatment initiation and lasted 12 days. The development of hypertension was verified by tail plethysmography technique. After the end of treatments, the animals were subjected to experimental protocols (6-12 animals per group; total number of animals used: 78). KEY FINDINGS: L-NAME hypertensive animals had no alterations in heart rate (HR) and intrinsic HR, but showed reduction in baroreflex sensitivity, parasympathetic tone, and gastric motility; and the sympathetic tone, chemoreflex sensitivity, and the LF (low frequency) band of systolic arterial pressure (SAP) variability were increased. DON or PYR attenuated the increase in mean arterial pressure (MAP) induced by L-NAME. Both anticholinesterase drugs were effective in preventing the decrease in baroreflex sensitivity, parasympathetic tone and gastric motility, and also prevented the increases in peripheral chemoreflex response and cardiac sympathetic tone. SIGNIFICANCE: Acetylcholinesterase inhibition with DON or PYR is a promising pharmacological approach to increase parasympathetic function, thus preventing the hypertension-induced alterations in the cardiovascular, gastrointestinal and autonomic systems.


Assuntos
Acetilcolinesterase/metabolismo , Inibidores da Colinesterase/farmacologia , Hipertensão/prevenção & controle , NG-Nitroarginina Metil Éster/efeitos adversos , Substâncias Protetoras/farmacologia , Brometo de Piridostigmina/farmacologia , Animais , Pressão Arterial/efeitos dos fármacos , Sistema Nervoso Autônomo/efeitos dos fármacos , Barorreflexo/efeitos dos fármacos , Sistema Cardiovascular/efeitos dos fármacos , Inibidores da Colinesterase/metabolismo , Modelos Animais de Doenças , Donepezila/metabolismo , Donepezila/farmacologia , Frequência Cardíaca , Hipertensão/metabolismo , Masculino , Substâncias Protetoras/metabolismo , Brometo de Piridostigmina/metabolismo , Ratos , Ratos Wistar , Estômago/efeitos dos fármacos , Volume Sistólico
10.
J Chromatogr A ; 1624: 461239, 2020 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-32540077

RESUMO

Effect-directed analysis (EDA) is increasingly used in environmental monitoring to detect and identify key toxicants. High-performance thin-layer chromatography (HPTLC) has proven to be a very suitable fractionation technique for this purpose. However, HPTLC is limited in its separation efficiency. Thus, separated fractions could still contain many different components and identification of the effective substances remains difficult. Therefore, in this study a workflow for selective EDA with two-dimensional HPTLC in combination with high-performance liquid chromatography-high-resolution mass spectrometry (HPLC-HRMS) was developed. The aim of the workflow was the stepwise reduction of the sample complexity in order to reduce the number of signals that could be responsible for the measured effects. As a consequence, the identification of effective substances should be facilitated. The acetylcholinesterase inhibition assay (AChE assay) for the detection of potential neurotoxic compounds was applied for biotesting. The transfer of effective zones from the first to the second dimension and also to the mass spectrometric measurement was enabled by extraction. A proof of concept was performed by spiking six acetylcholinesterase inhibiting substances into three different water matrices that were investigated with the developed workflow. The successful prioritization of all spiked compounds confirmed the efficiency of the workflow, regardless of the sample matrix. Biotesting of different water samples resulted in numerous potentially neurotoxic effects, which overlapped strongly in the first separation dimension. The higher peak capacity reached by two-dimensional HPTLC, on the other hand, resulted in discrete effective zones and enabled the identification of several compounds. For the substances lumichrome, a derivate of riboflavin and paraxanthine as well as for linear alkylbenzene sulfonates that were applied as anionic surfactants in detergents, the inhibiting effect to the AChE could be confirmed.


Assuntos
Inibidores da Colinesterase/análise , Cromatografia em Camada Delgada/métodos , Espectrometria de Massas/métodos , Água/química , Acetilcolinesterase/metabolismo , Ensaios Enzimáticos , Fluorescência , Processamento de Sinais Assistido por Computador , Poluentes Químicos da Água/análise
11.
Food Chem ; 327: 127045, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32464460

RESUMO

In this study, the inhibitory potentials of food originated 34 phenolic acids, and flavonoid compounds were screened against acetylcholinesterase, butyrylcholinesterase, urease, and tyrosinase enzymes. All compounds included in this study exhibited high antioxidant activity with an ignorable cytotoxic activity. In general, they also showed poor anti-urease and anti-tyrosinase activities. Compounds in aglycone form (quercetin, myricetin, chrysin, and luteolin) showed strong anticholinesterase activities. No relation was observed between the tested bioactivities except from the case that aglycone compounds exhibited a strong positive relationship between antioxidant activities and anticholinesterase activity. Interestingly, there was a relation between the molecular weights of aglycone compounds and their anticholinesterase activities. The study showed that flavonoids with molecular mass of 250-320 g/mol have high potential of anticholinesterase activities and are valuable for future experiments on animals and humans. Potential inhibitory effects of these molecules on target proteins were investigated using docking and molecular dynamics calculations.


Assuntos
Inibidores da Colinesterase/química , Flavonoides/química , Hidroxibenzoatos/química , Plantas Comestíveis/química , Acetilcolinesterase/química , Acetilcolinesterase/metabolismo , Animais , Antioxidantes/química , Sítios de Ligação , Domínio Catalítico , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Inibidores da Colinesterase/metabolismo , Inibidores da Colinesterase/farmacologia , Flavonoides/metabolismo , Flavonoides/farmacologia , Humanos , Hidroxibenzoatos/metabolismo , Simulação de Acoplamento Molecular , Monofenol Mono-Oxigenase/antagonistas & inibidores , Monofenol Mono-Oxigenase/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/química , Plantas Comestíveis/metabolismo
12.
Chem Biol Interact ; 326: 109139, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32454005

RESUMO

Since several decades oximes have been used as part of treatment of nerve agent intoxication with the aim to restore the biological function of the enzyme acetylcholinesterase after its covalent inhibition by organophosphorus compounds such as pesticides and nerve agents. Recent findings have illustrated that, besides oximes, certain Mannich phenols can reactivate the inhibited enzyme very effectively, and may therefore represent an attractive complementary class of reactivators. In this paper we further probe the effect of structural variation on the in vitro efficacy of Mannich phenol based reactivators. Thus, we present the synthesis of 14 compounds that are close variants of the previously reported 4-amino-2-(1-pyrrolidinylmethyl)-phenol, a very effective non-oxime reactivator, and 3 dimeric Mannich phenols. All compounds were assessed for their ability to reactivate human acetylcholinesterase inhibited by the nerve agents VX, tabun, sarin, cyclosarin and paraoxon in vitro. It was confirmed that the potency of the compounds is highly sensitive to small structural changes, leading to diminished reactivation potency in many cases. However, the presence of 4-substituted alkylamine substituents (as exemplified with the 4-benzylamine-variant) was tolerated. More surprisingly, the dimeric compounds demonstrated non-typical behavior and displayed some reactivation potency as well. Both findings may open up new avenues for designing more effective non-oxime reactivators.


Assuntos
Acetilcolinesterase/metabolismo , Inibidores da Colinesterase/química , Inibidores da Colinesterase/farmacologia , Agentes Neurotóxicos/química , Agentes Neurotóxicos/farmacologia , Oximas/química , Oximas/farmacologia , Substâncias para a Guerra Química/química , Substâncias para a Guerra Química/farmacologia , Reativadores da Colinesterase/metabolismo , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Humanos , Relação Estrutura-Atividade
13.
Ecotoxicol Environ Saf ; 199: 110751, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32446104

RESUMO

Tonalide or acetyl hexamethyl tetralin (AHTN) is used as a fragrance additive in various household products. Recently, AHTN has drawn attention owing to its negative health effects on aquatic organisms. Data on AHTN toxicity toward aquatic species are limited. Therefore, this study tested the oxidative stress induced by AHTN exposure on the Rhodeinae sinensis Gunther and Macrobrachium nipponense. In this study, malonaldehyde (MDA) content and the activities of acetyl cholinesterase (AchE), superoxide dismutase (SOD), glutathione S-transferase (GST), and catalase (CAT) in R. sinensis Gunther were tested after 30 days of exposure to 30.093, 34.005, 38.426, 43.421, 49.067, 55.444, 62.652, 70.800, and 80.000 µg/L AHTN, respectively. The MDA, AchE, SOD, GST and CAT in M. nipponense were tested after 40 days of exposure to 60.000, 72.000, 86.400, 103.680, 124.416, 149.299, 179.159, 214.991, and 257.989 µg/L AHTN, respectively. In addition, an integrated biomarker response (IBR) index was utilised to evaluate the integrated toxic effects of AHTN on R. sinensis Gunther and M. nipponense. Finally, the predicted no-effect concentrations (PNECs) of AHTN, based on reproduction, biochemistry, survival, chronic toxicity, and acute toxicity endpoints were derived. The results indicated that low concentrations of AHTN can induce significant changes of oxidative stress biomarkers. The no observed effect concentrations (NOECs) of SOD, GST, AchE, CAT, and MDA were 103.680, 72.000, <60.000, 72.000, and <60.000 µg/L for R. sinensis Gunther and 38.426, 43.421, 30.093, 30.093, and 38.426 µg/L for M. nipponense, respectively. The IBR calculation results showed that 149.299 µg/L AHTN caused the highest toxic effect on R. sinensis Gunther after 30 days of exposure, whereas 70.797 µg/L AHTN caused the greatest damage to M. nipponense after 40 days of exposure. The PNECs of AHTN based on the non-traditional endpoints of biochemistry and reproduction were 0.00145 µg/L and 0.000395 µg/L, respectively, which were significantly lower than the PNEC of 2.636 µg/L for traditional endpoint survival. Therefore, the protection of aquatic organisms based on non-traditional toxicity endpoints should be considered in ecological risk assessment.


Assuntos
Antioxidantes/metabolismo , Organismos Aquáticos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Palaemonidae/efeitos dos fármacos , Perfumes/toxicidade , Tetra-Hidronaftalenos/toxicidade , Poluentes Químicos da Água/toxicidade , Acetilcolinesterase/metabolismo , Animais , Organismos Aquáticos/enzimologia , Catalase/metabolismo , Relação Dose-Resposta a Droga , Determinação de Ponto Final , Glutationa Transferase/metabolismo , Malondialdeído/metabolismo , Nível de Efeito Adverso não Observado , Palaemonidae/enzimologia , Valor Preditivo dos Testes , Superóxido Dismutase/metabolismo
14.
Food Chem ; 324: 126889, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32353659

RESUMO

Pesticides have been extensively applied worldwide to protect crops from worms and insects; however, the continuous use of pesticides affects ecosystems, agricultural product safety, nontarget organisms, and human health. In this paper, we report a highly sensitive biosensor for the determination of pesticides based on tin sulfide (SnS2) and chitosan (CHIT) nanocomposites decorated with a unique British housefly acetylcholinesterase (AChE). The hydrothermally synthesized nano-SnS2 mixed with chitosan solution (CHIT-SnS2) was drop-casted onto a glassy carbon electrode (GCE). Subsequently, the British housefly AChE was immobilized on the CHIT/SnS2-coated GCE that was then employed for pesticide detection. The developed biosensor showed an ultra-high sensitivity and wide linear detection range from 0.02 nM to 20000 nM with a detection limit of 0.02 nM for the detection of chlorpyrifos as the model pesticide. Furthermore, the AChE/CHIT-SnS2/GCE exhibited acceptable storage stability, good reproducibility, and selectivity.


Assuntos
Acetilcolinesterase/metabolismo , Técnicas Biossensoriais/métodos , Quitosana/química , Moscas Domésticas/enzimologia , Compostos Organofosforados/análise , Sulfetos/química , Compostos de Estanho/química , Acetilcolinesterase/química , Animais , Carbono/química , Clorpirifos/análise , Técnicas Eletroquímicas , Eletrodos , Enzimas Imobilizadas/química , Enzimas Imobilizadas/metabolismo , Limite de Detecção , Nanocompostos/química , Praguicidas/análise , Reprodutibilidade dos Testes
15.
PLoS One ; 15(5): e0232747, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32374765

RESUMO

The potential effects of Bt (Bacillus thuringiensis) maize on non-target organisms must be conducted before the Bt maize is commercially planted. Folsomia candida is one of the non-target organisms of Bt maize, also as an important indicator of soil quality and environmental pollution. In this study, a 90-day F. candida feeding test were conducted to evaluate the potential effects of two Bt maize lines IE09S034 and BT799 and their non-Bt conventional isolines Zong 31 and Zheng 58. The results show that Bt maize lines had no significant effects on the survival rate, reproduction, adult body length, larval body length, and the activities of acetyl cholinesterase, catalase and superoxide dismutase on the F. candida. Namely, Bt maize had no toxic effects on the F. candida.


Assuntos
Bacillus thuringiensis/genética , Candida/metabolismo , Folhas de Planta/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Zea mays/genética , Acetilcolinesterase/metabolismo , Animais , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Bioensaio/métodos , Catalase/metabolismo , Endotoxinas/genética , Endotoxinas/metabolismo , Proteínas Hemolisinas/genética , Proteínas Hemolisinas/metabolismo , Larva , Reprodução/genética , Microbiologia do Solo , Superóxido Dismutase/metabolismo , Zea mays/microbiologia
16.
PLoS One ; 15(4): e0231981, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32348360

RESUMO

An acetylcholinesterase biosensor modified with graphene and transition metal carbides was prepared to detect organophosphorus pesticides. Cyclic voltammetry, differential pulse voltammetry, and electrochemical impedance spectroscopy were used to characterize the electrochemical catalysis of the biosensor: acetylcholinesterase/chitosan-transition metal carbides/graphene/glassy carbon electrode. With the joint modification of graphene and transition metal carbides, the biosensor has a good performance in detecting dichlorvos with a linear relationship from 11.31 µM to 22.6 nM and the limit of detection was 14.45 nM. Under the premise of parameter optimization, the biosensor showed a good catalytic performance for acetylcholine. Compared to the biosensors without modification, it expressed a better catalytic performance due to the excellent electrical properties, biocompatibility and high specific surface area of graphene, transition metal carbides. Finally, the biosensor exhibits good stability, which can be stored at room temperature for one month without significant performance degradation, and has practical potential for sample testing.


Assuntos
Acetilcolinesterase/metabolismo , Técnicas Biossensoriais/métodos , Grafite/química , Nanocompostos/química , Compostos Organofosforados/análise , Praguicidas/análise , Técnicas Eletroquímicas , Eletrodos , Enzimas Imobilizadas/química , Enzimas Imobilizadas/metabolismo , Limite de Detecção , Reprodutibilidade dos Testes , Titânio/química , Elementos de Transição/química
17.
Life Sci ; 250: 117585, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32243928

RESUMO

AIMS: Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) have been associated with risk factors for metabolic syndrome (MetS). Our objective was to evaluate the effect of nicotinamide (NAM) on the activities, expression and protein content of cholinesterases in a MetS model. MAIN METHODS: MetS was induced in male rats administrating 40% fructose to the drinking water for 16 weeks. Additionally, from 5th week onward, the carbohydrate solution was replaced by NAM, at several concentrations for 5 h each morning for the next 12 weeks. In the 15th week, the glucose tolerance test was conducted, and blood pressure was measured. After the treatment period had concluded, the biochemical profile; oxidant stress; proinflammatory markers; and the activity, quantity and expression of cholinesterases were evaluated, and molecular docking analysis was performed. KEY FINDINGS: The MetS group showed anthropometric, hemodynamic and biochemical alterations and increased cholinesterase activity, inflammation and stress markers. In the liver, cholinesterase activity and mRNA, free fatty acid, tumor necrosis factor-alpha (TNF-α), and thiobarbituric acid-reactive substance (TBARS) levels were increased, while reduced glutathione (GSH) levels were decreased. NAM partially or totally decreased risk factors for MetS, markers of stress and inflammation, and the activity (serum and liver) and expression (liver) of cholinesterases. Molecular docking analysis showed that NAM has a greater affinity for cholinesterases than acetylcholine (ACh), suggesting NAM as an inhibitor of cholinesterases. SIGNIFICANCE: Supplementation with 40% fructose induced MetS, which increased the activity and expression of cholinesterases, oxidative stress and the inflammation. NAM attenuated these MetS-induced alterations and changes in cholinesterases.


Assuntos
Inflamação/metabolismo , Síndrome Metabólica/tratamento farmacológico , Niacinamida/uso terapêutico , Estresse Oxidativo , Receptores Colinérgicos/metabolismo , Acetilcolinesterase/metabolismo , Animais , Antropometria , Anti-Inflamatórios/uso terapêutico , Arildialquilfosfatase/metabolismo , Butirilcolinesterase/metabolismo , Colinesterases/metabolismo , Frutose , Regulação da Expressão Gênica , Teste de Tolerância a Glucose , Hemodinâmica , Humanos , Peroxidação de Lipídeos , Fígado/enzimologia , Masculino , Síndrome Metabólica/induzido quimicamente , Simulação de Acoplamento Molecular , Ratos , Ratos Sprague-Dawley
18.
Toxicology ; 438: 152463, 2020 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-32294493

RESUMO

Methyl parathion (Me-Pa) is an extremely toxic organophosphorus pesticide still used in developing countries. It has been associated with decreased sperm function and fertility and with oxidative and DNA damage. The blood-testis barrier (BTB) is a structure formed by tight junction (TJ) proteins in Sertoli cells and has a critical role in spermatogenesis. We assessed the effect of repeated doses of Me-Pa (3-12 mg/kg/day for 5 days, i.p.) on sperm quality, lipid oxidation, DNA integrity, and BTB permeability in adult male mice and explored oxidation as a mechanism of toxicity. Me-Pa caused dose-dependent effects on sperm quality, lipoperoxidation, and DNA integrity. Testis histology results showed the disruption of spermatogenesis progression and atrophy of seminiferous tubules. The pesticide opened the BTB, as evidenced by the presence of a biotin tracer in the adluminal compartment of the seminiferous tubules. This effect was not observed after 45 days of exposure when a spermatogenic cycle had completed. The coadministration of the antioxidant α-tocopherol (50 mg/kg/day for 5 days, oral) prevented the effects of Me-Pa on sperm quality, DNA and the BTB, indicating the importance of oxidative stress in the damage generated by Me-Pa. As evidenced by immunochemistry, no changes were found in the localization of the TJ proteins of the BTB, although oxidation (carbonylation) of total proteins in testis homogenates was detected. Our results show that Me-Pa disturbs the BTB and that oxidation is involved in the observed toxic effects on sperm cells.


Assuntos
Barreira Hematotesticular/efeitos dos fármacos , Permeabilidade Capilar/efeitos dos fármacos , Inibidores da Colinesterase/toxicidade , Dano ao DNA , Metil Paration/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Praguicidas/toxicidade , Espermatozoides/efeitos dos fármacos , Acetilcolinesterase/metabolismo , Animais , Antioxidantes/farmacologia , Barreira Hematotesticular/metabolismo , Barreira Hematotesticular/patologia , Proteínas Ligadas por GPI/antagonistas & inibidores , Proteínas Ligadas por GPI/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Camundongos Endogâmicos ICR , Carbonilação Proteica/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Espermatozoides/metabolismo , Espermatozoides/patologia
19.
Food Chem ; 320: 126683, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32229401

RESUMO

Here, we demonstrate use of acetylcholinesterase (AChE)-responsive polyoxometalate (POM)/surfactant supramolecular spheres to build a liquid crystal (LC)-based sensing platform for detection of organophosphorus pesticides. The self-assembled spheres are composed of hybrid materials of a POM, sodium dodecatungstophosphate (PW12), and a surfactant, myristoylcholine (Myr). It displays dark appearance when the aqueous solution is in contact with LCs supported on the octadecyltrichlorosilane-treated glass deposited with the supramolecular spheres, suggesting perpendicular orientation of LCs at the aqueous/LC interface. In contrast, LCs show bright appearance when the surface-deposited supramolecular spheres are enzymatically hydrolyzed by AChE, corresponding to planar orientation of LCs at the aqueous/LC interface. Detection of organophosphates are successfully achieved as they are potent inhibitors of AChE. The detection limit of the sensing platform reached 0.9 ng/mL for dimethoate. This method can avoid disturbance of external interference with excellent specificity and sensitivity, which makes it very promise in detection of organophosphorus pesticides.


Assuntos
Acetilcolinesterase/metabolismo , Análise de Alimentos/métodos , Cristais Líquidos/química , Praguicidas/análise , Análise de Alimentos/instrumentação , Hidrólise , Lagos/análise , Limite de Detecção , Compostos Organofosforados/análise , Silanos/química , Tensoativos/química , Compostos de Tungstênio/química , Água/química , Poluentes Químicos da Água/análise
20.
Ecotoxicol Environ Saf ; 197: 110608, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32305822

RESUMO

Graphene oxide (GO) has broad application potential in many fields, such as biomedicine and energy. Due to the wide-ranging GO applications, its entry into the environment is inevitable along with the potential for ecological and environmental risks. In the present study, we systematically investigated the dose-dependent effects of three different-sized GO particles (50-200 nm, <500 nm, and >500 nm) on zebrafish during the very early developmental stages (4-124 h post-fertilization). The results showed that GOs could accumulate in the eyes, heart, yolk sac, and blood vessels of fish larvae. Consequently, their effects on multiple toxic endpoints were observed, including delayed hatching times, shortened body lengths, alterations in heart rate and blood flow, changes in swimming activity and responses to photoperiod stimulation, and the enhanced activity of total superoxide dismutase, inducible nitric oxide synthase, acetylcholinesterase, caspase-3, and induction of apoptosis-related gene expression. As a result, the occurrence of oxidative stress and the induction of apoptosis are suggested in fish larvae exposed to all three different-sized GO particles. In addition, our results highlight the impacts of waterborne-GO exposure on zebrafish during early development, which were not merely dependent on GO concentration but also on the associated GO sizes. This study hereby provides a basis for the potential ecological and health risks of GO exposure.


Assuntos
Poluentes Ambientais/toxicidade , Grafite/toxicidade , Acetilcolinesterase/metabolismo , Animais , Apoptose/genética , Caspase 3/metabolismo , Embrião não Mamífero/efeitos dos fármacos , Desenvolvimento Embrionário/efeitos dos fármacos , Poluentes Ambientais/farmacocinética , Expressão Gênica/efeitos dos fármacos , Grafite/farmacocinética , Larva/efeitos dos fármacos , Larva/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Tamanho da Partícula , Superóxido Dismutase/metabolismo , Peixe-Zebra/embriologia , Peixe-Zebra/metabolismo
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