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1.
Environ Sci Technol ; 55(3): 1585-1593, 2021 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-33470798

RESUMO

Hydrolysis catalyzed by general esterases (GEs) is the most efficient route for hydrolyzation of pyrethroid insecticides. Organophosphate (OP) and carbamate (CB) insecticides are known to inhibit GEs in addition to acetylcholinesterase (AChE), which is their main target. We hypothesize that synergies can be induced by OPs and CBs when mixed with pyrethroids, due to their inhibition of GE-dependent detoxification of pyrethroids. To test this hypothesis, we conducted mixture toxicity experiments with Daphnia magna using α-cypermethrin (α-cyp) in combination with the noninsecticidal OP tetraisopropyl pyrophosphoramide (iso-OMPA) and five AChE inhibitors diazinon, chlorpyrifos, chlorfenviphos, parathion, and aldicarb. In addition, the in vivo GE activity inhibition was measured for all compounds. Up to 10-fold synergy was found between α-cyp and iso-OMPA, and the degree of synergy correlated linearly with the inhibition of the GE activity. No synergy, however, was found in any of the insecticide mixtures nor was the GE activity inhibited within the nonlethal concentration range tested. It was concluded that the effect of the insecticides on AChE occurred at lower concentrations than their effect on GEs, making the daphnids become immobilized before any synergistic effects on mortality could be observed. The implications of the findings are discussed from a risk assessment perspective.


Assuntos
Inseticidas , Piretrinas , Acetilcolinesterase/metabolismo , Animais , Biotransformação , Carbamatos/toxicidade , Inibidores da Colinesterase , Esterases , Inseticidas/toxicidade , Organofosfatos/toxicidade , Piretrinas/toxicidade
2.
Ecotoxicol Environ Saf ; 205: 111157, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32829211

RESUMO

The fungicide carbendazim (CBM) has been applied all around the world but its potential adverse effects other than its recognized activity as endocrine disruptor in non target organisms have been scarcely studied. The aims of this work were (1) to use a battery of biomarkers that can reflect potential negative effects such as oxidative stress, genotoxicity, neurotoxicity or altered immune response; and (2) to examine biomarkers of detoxification by analyzing the gene expression of cytochrome P4501A1 (CYP1A1) and the multi-xenobiotic resistance protein P-glycoprotein (P-gp) in the freshwater fish Jenynsia multidentata exposed to environmentally relevant concentrations of CBM during 24 h. Fish exposed to 5 µg/L showed inhibition of GST activity and an increase of TBARs contents in gills, the organ of direct contact with waterborne contaminants. Genotoxicity - measured in peripheral blood-was evidenced by the increases of micronuclei frequency when fish were exposed to 5, 10 and 100 µg/L CBM and of nuclear abnormalities (NA) frequency at 0.05, 0.5, 5, 10 and 100 µg/L CBM. The expression inhibition of interleukin (IL-1ß) and tumor necrosis factor a (TNF-α) at 10, and 5 and 10 µg/L CBM, respectively, indicated an altered immune response. The expression of CYP1A1 was down regulated in liver at 10 µg/L and of P-gp at 5 µg/L CBM, indicating a possible slow on CBM metabolization. On the other hand, in gills CYP1A1 decreased at 5 and 10 µg/L while P-gp was induced at 5 and 100 µg/L CBM. Overall, most of these significant effects were detected below 10 µg/L CBM, in a range of realistic concentrations in aquatic ecosystems worldwide.


Assuntos
Benzimidazóis/toxicidade , Carbamatos/toxicidade , Ciprinodontiformes/metabolismo , Citocinas/metabolismo , Micronúcleos com Defeito Cromossômico/induzido quimicamente , Estresse Oxidativo/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Animais , Antioxidantes/metabolismo , Biomarcadores/metabolismo , Ciprinodontiformes/genética , Ciprinodontiformes/imunologia , Citocromo P-450 CYP1A1/genética , Ecossistema , Água Doce/química , Brânquias/efeitos dos fármacos , Brânquias/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Estresse Oxidativo/genética , Estresse Oxidativo/imunologia
3.
PLoS One ; 15(7): e0229052, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32614853

RESUMO

Rice paddy irrigation ponds can sustain surprisingly high taxonomic richness and make significant contributions to regional biodiversity. We evaluated the impacts of pesticides and other environmental stressors (including eutrophication, decreased macrophyte coverage, physical habitat destruction, and invasive alien species) on the taxonomic richness of freshwater animals in 21 irrigation ponds in Japan. We sampled a wide range of freshwater animals (reptiles, amphibians, fishes, mollusks, crustaceans, insects, annelids, bryozoans, and sponges) and surveyed environmental variables related to pesticide contamination and other stressors listed above. Statistical analyses comprised contraction of highly correlated environmental variables, best-subset model selection, stepwise model selection, and permutation tests. Results showed that: (i) probenazole (fungicide) was a significant stressor on fish (i.e., contamination with this compound had a significantly negative correlation with fish taxonomic richness), (ii) the interaction of BPMC (insecticide; also known as fenobucarb) and bluegill (invasive alien fish) was a significant stressor on a "large insect" category (Coleoptera, Ephemeroptera, Hemiptera, Lepidoptera, Odonata, and Trichoptera), (iii) the interaction of BPMC and concrete bank protection was a significant stressor on an "invertebrate" category, (iv) the combined impacts of BPMC and the other stressors on the invertebrate and large insect categories resulted in an estimated mean loss of taxonomic richness by 15% and 77%, respectively, in comparison with a hypothetical pond with preferable conditions.


Assuntos
Invertebrados/efeitos dos fármacos , Praguicidas/toxicidade , Animais , Biodiversidade , Carbamatos/toxicidade , Ecossistema , Monitoramento Ambiental , Espécies Introduzidas , Invertebrados/fisiologia , Tanques , Tiazóis/toxicidade , Vertebrados/fisiologia
4.
Ecotoxicol Environ Saf ; 201: 110729, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32485491

RESUMO

The transformation of carbosulfan (CSN) in apples was investigated during oven-drying, microwave drying, and sun-drying. CSN transformed primarily into carbofuran (COA) during these drying processes. The conversion kinetics of CSN and COA was fitted by curve regression and mainly conformed to quadratic models (R2 = 0.70-0.97). Oven-drying promoted the transformation of CSN into COA. Microwave drying resulted in the highest scavenging capacity against CSN and COA (41%-100%). Moreover, a transformation mechanism was proposed on the basis of density functional theory (DFT) calculation. The COA originated from a series of chemical reactions involving hydroxyl substitution, cleavage, and oxidation; this result was further confirmed on the basis of molecular electrostatic potential (MEP) and molecular orbital theory. Furthermore, the toxicity and stability of CSN and COA were evaluated with the T.E.S.T. program. COA was less toxic than CSN to aquatic organisms but more toxic than CSN to rats. Therefore, COA production should be avoided during drying. Microwave drying was found to be the optimum choice for drying apples.


Assuntos
Carbamatos/metabolismo , Dessecação/métodos , Manipulação de Alimentos/métodos , Malus/química , Animais , Organismos Aquáticos/efeitos dos fármacos , Carbamatos/química , Carbamatos/toxicidade , Carbofurano/química , Carbofurano/metabolismo , Carbofurano/toxicidade , Dessecação/instrumentação , Manipulação de Alimentos/instrumentação , Depuradores de Radicais Livres/análise , Ratos
5.
Chemosphere ; 255: 126871, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32413796

RESUMO

Research efforts into the potential side-effects of pesticides on beneficial organisms have focused on temperate test species and conditions. There is thus a need for studies into the ecotoxicity of a vaster range of pesticides under tropical conditions. The present study therefore aimed to compare the acute and chronic toxicity of the fungicide carbendazim to the earthworm Eisenia fetida under tropical and temperate conditions. To this end, laboratory toxicity tests were conducted with a tropical and European strain of E. fetida, using different artificial (OECD and TAS) and natural (LUFA and TNS) soils, and under different test temperatures (20 °C and 28 °C). In the acute lethality tests with artificial soils, the tropical strain of E. fetida was three to four order of magnitude less sensitive than the European strain, which is ascribed to the higher test temperature and (hence) higher microbial activity/pesticide degradation. The tropical strain was particularly sensitive in the tropical natural soil, which was attributed to the low pH (3.9) of this soil. The chronic toxicity tests overall also showed a lower sensitivity of the tropical strain on reproduction. These findings thus support the use of toxicity data generated under temperate conditions in tropical pesticide effect assessments. However, intensive agricultural practices in the tropics may dictate that exposure levels (and hence potentially also risks) are higher.


Assuntos
Benzimidazóis/toxicidade , Carbamatos/toxicidade , Fungicidas Industriais/toxicidade , Agricultura , Animais , Laboratórios , Oligoquetos/efeitos dos fármacos , Praguicidas/toxicidade , Solo/química , Poluentes do Solo/análise , Poluentes do Solo/toxicidade
6.
Eur J Med Chem ; 197: 112282, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32380361

RESUMO

Compounds capable of interacting with single or multiple targets involved in Alzheimer's disease (AD) pathogenesis are potential anti-Alzheimer's agents. In our aim to develop new anti-Alzheimer's agents, a series of 36 new N-alkylpiperidine carbamates was designed, synthesized and evaluated for the inhibition of cholinesterases [acetylcholinesterase (AChE) and butyrylcholinesterase (BChE)] and monoamine oxidases [monoamine oxidase A (MAO-A and monoamine oxidase B (MAO-B)]. Four compounds are very promising: multiple AChE (IC50 = 7.31 µM), BChE (IC50 = 0.56 µM) and MAO-B (IC50 = 26.1 µM) inhibitor 10, dual AChE (IC50 = 2.25 µM) and BChE (IC50 = 0.81 µM) inhibitor 22, selective BChE (IC50 = 0.06 µM) inhibitor 13, and selective MAO-B (IC50 = 0.18 µM) inhibitor 16. Results of enzyme kinetics experiments showed that despite the carbamate group in the structure, compounds 10, 13, and 22 are reversible and non-time-dependent inhibitors of AChE and/or BChE. The resolved crystal structure of the complex of BChE with compound 13 confirmed the non-covalent mechanism of inhibition. Additionally, N-propargylpiperidine 16 is an irreversible and time-dependent inhibitor of MAO-B, while N-benzylpiperidine 10 is reversible. Additionally, compounds 10, 13, 16, and 22 should be able to cross the blood-brain barrier and are not cytotoxic to human neuronal-like SH-SY5Y and liver HepG2 cells. Finally, compounds 10 and 16 also prevent amyloid ß1-42 (Aß1-42)-induced neuronal cell death. The neuroprotective effects of compound 16 could be the result of its Aß1-42 anti-aggregation effects.


Assuntos
Carbamatos/farmacologia , Inibidores da Colinesterase/farmacologia , Inibidores da Monoaminoxidase/farmacologia , Fármacos Neuroprotetores/farmacologia , Piperidinas/farmacologia , Acetilcolinesterase/metabolismo , Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/metabolismo , Butirilcolinesterase/metabolismo , Carbamatos/síntese química , Carbamatos/toxicidade , Linhagem Celular Tumoral , Inibidores da Colinesterase/síntese química , Inibidores da Colinesterase/toxicidade , Desenho de Fármacos , Humanos , Estrutura Molecular , Inibidores da Monoaminoxidase/síntese química , Inibidores da Monoaminoxidase/toxicidade , Fármacos Neuroprotetores/síntese química , Fármacos Neuroprotetores/toxicidade , Fragmentos de Peptídeos/metabolismo , Piperidinas/síntese química , Piperidinas/toxicidade , Multimerização Proteica/efeitos dos fármacos , Relação Estrutura-Atividade
7.
Toxicology ; 440: 152490, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32418910

RESUMO

Testicular injury is often observed in drug development. Serum hormones are usually used as noninvasive biomarkers for testicular injury; however, their sensitivities are low. Therefore, it is difficult to monitor testicular injury in drug development. In recent years, molecules in body fluid exosomes have attracted attention as biomarkers for diseases. In this study, small RNAs in serum exosomes were analyzed to identify noninvasive biomarkers of testicular injury in rats, which are often used in preclinical drug development. The rat models of testicular injury were prepared by a single oral administration of 2000 mg/kg ethylene glycol monomethyl ether, in which spermatocyte degeneration and Sertoli cell vacuolation were observed, or 400 mg/kg carbendazim, in which Sertoli cell vacuolation and seminiferous tubule dilation were observed. Serum exosomal small RNA-seq analysis of these models was performed. The analysis identified 3 small RNAs that fluctuated in common between the models, and miR-423-5p and miR-128-3p were selected as candidate markers. For evaluating these candidate markers in other testicular injury models, the models were prepared by a single oral administration of 60 mg/kg 1,3-dinitrobenzene or 500 mg/kg nitrofurazone, and spermatocyte degeneration and Sertoli cell vacuolation were observed. In qPCR analysis, these exosomal miRNAs were upregulated in all models except for the 1,3-dinitrobenzene model, in which severe hemolysis was observed. By contrast, these miRNAs in whole serum extracts did not significantly change in any of the models. In conclusion, we identified miR-423-5p and miR-128-3p in serum exosomes as noninvasive biomarkers for testicular injury in rats.


Assuntos
Biomarcadores/análise , Exossomos/química , RNA Citoplasmático Pequeno/análise , Doenças Testiculares/diagnóstico , Animais , Benzimidazóis/toxicidade , Carbamatos/toxicidade , Dinitrobenzenos/toxicidade , Masculino , MicroRNAs/efeitos dos fármacos , Nitrofurazona/toxicidade , Ratos , Ratos Sprague-Dawley , Células de Sertoli/química , Células de Sertoli/patologia , Espermatócitos/química , Espermatócitos/efeitos dos fármacos , Vacúolos/efeitos dos fármacos , Vacúolos/patologia
8.
Environ Res ; 187: 109646, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32460093

RESUMO

BACKGROUND: A growing body of evidences suggests an association between early exposure to organophosphates (OPs), organochlorines (OCs), pyrethroids or carbamates and autism spectrum disorder (ASD). However, there are limited data about the other pesticide groups, especially in Europe. OBJECTIVES: Based on a systematic review, we aimed to assess the influence of neuro- and thyrotoxic agricultural and domestic pesticides (other than OPs, OCs, pyrethroids and carbamates) authorized in Europe on risk of ASD in children or ASD behavioral phenotypes in rodents. METHODS: Pesticides were initially identified in the Hazardous Substances Data Bank. 20 currently used (10 pesticide groups) were retained based on the higher exposure potential. Epidemiological (children) and in vivo (rodents) studies were identified through PubMed, Web of Science and TOXLINE, without restriction of publication date or country (last update: November 2019). The risk of bias and level of evidence were also assessed. This systematic review is registered at the International Prospective Register of Systematic Reviews (PROSPERO, registration number CRD42019145384). RESULTS: In total, two epidemiological and 15 in vivo studies were retained, focusing on the azole, neonicotinoid, phenylpyrazole and phosphonoglycine pesticide groups. No study was conducted in Europe. Glyphosate, imidacloprid, clothianidin, myclobutanil, acetamiprid, tebuconazole, thiabendazole and fipronil, globally reported an association with an increased risk of ASD in children and/or ASD behavioral phenotypes in rodents. In children, glyphosate and myclobutanil showed a "moderate level of evidence" in their association with ASD, whereas imidacloprid showed an "inadequate level of evidence". In rodents, clothianidin, imidacloprid and glyphosate showed a "high level of evidence" in their association with altered behavioral, learning and memory skills. CONCLUSION: In the framework of environmental risk factors of ASD, novel hypotheses can be formulated about early exposure to eight pesticides. Glyphosate presented the most salient level of evidence. Given their neuro- and thyrotoxic properties, additional studies are needed for the 12 other pesticides not yet studied as potential ASD risk factors according to our inclusion criteria.


Assuntos
Transtorno do Espectro Autista , Praguicidas , Piretrinas , Transtorno do Espectro Autista/epidemiologia , Carbamatos/toxicidade , Criança , Europa (Continente)/epidemiologia , Humanos , Organofosfatos/toxicidade , Praguicidas/toxicidade , Piretrinas/toxicidade
9.
J Environ Sci Health B ; 55(5): 429-437, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32065017

RESUMO

We evaluated the real effects of pollutants through a multi-generation study. We tested whether short-term exposure (48 h) of successive (first and second) generations of Chironomus yoshimatsui neonates (<24-h-old) to two acetylcholinesterase inhibitor insecticides, pyraclofos, and pirimicarb, would change insecticide sensitivity and life-cycle parameters over four generations. Additionally, we tested whether acetylcholinesterase (AChE) activity levels would be associated with this sensitivity change. Sensitivities (48 h EC50 value, using immobility as the endpoint) in chironomids (<24-h-old) and insect life-cycle parameters (the number of larvae per egg mass and adult size) were investigated. Parental chironomids produced larvae that were less sensitive than those in the control group following the two 48 h pirimicarb exposure events, whereas exposure to pyraclofos did not affect sensitivity. The AChE activity in larvae with low sensitivity to pirimicarb was significantly higher than that in the control. Thus, increased AChE activity might be associated with low sensitivity. The life-cycle parameters in chironomids recovered from the effects of pyraclofos and pirimicarb suggested they could adapt to the insecticides by changing biomass allocation. Our study suggested potential chemical risks of insecticide stress and how aquatic organisms adapt to it.


Assuntos
Carbamatos/toxicidade , Chironomidae/efeitos dos fármacos , Inibidores da Colinesterase/toxicidade , Inseticidas/toxicidade , Organotiofosfatos/toxicidade , Pirimidinas/toxicidade , Adaptação Biológica/efeitos dos fármacos , Animais , Chironomidae/fisiologia , Ecotoxicologia/métodos , Larva/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade
10.
Ecotoxicol Environ Saf ; 191: 110175, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31954924

RESUMO

Prosulfocarb (PSC) is a thiocarbamate herbicide mainly used in winter cereals and a relevant aerosol precursor under OH radicals (OH) photooxidation conditions. We investigated the environmental risks, mechanisms, kinetics and products for the PSC withOH by employing theoretical chemical calculations. Two reaction types of H-abstraction andOH-addition reactions were taken into account. Whether in the atmosphere or aqueous particles, the most favorable pathway was the H-abstraction in the N-alkyl groups close to nitrogen atom. Subsequent reactions of primary intermediates were considered at different conditions. The total rate constants were determined as 2.62 × 10-10 cm3 molecule-1 s-1 and 4.96 × 10-11 cm3 molecule-1 s-1 at 298 K in atmosphere and aqueous particles, respectively. In natural water with theOH concentration of 10-15-10-18 mol l-1, the half-lives (t1/2) of PSC in theOH-initiated reactions were calculated as t1/2 = 2.40 × 104-2.40 × 107 s. With regard to the influence on human health and the ecosystem, oxidized products of PSC were estimated to be mutagenicity negative and had no obvious bioaccumulation potential. The aquatic toxicity of PSC and its degradation products was evaluated and the assessment results showed that the degradation of PSC was a toxicity-reduced process but they were still at toxic and harmful levels.


Assuntos
Aerossóis/química , Carbamatos/química , Poluentes Ambientais/química , Herbicidas/química , Radical Hidroxila/química , Aerossóis/toxicidade , Carbamatos/toxicidade , Poluentes Ambientais/toxicidade , Meia-Vida , Herbicidas/toxicidade , Cinética , Oxirredução , Medição de Risco
11.
Chemosphere ; 242: 125293, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31896202

RESUMO

The effects produced by the ethyl-carbamates: ethyl-4-bromophenyl carbamate (LQM 919) and ethyl-4-chlorophenyl carbamate (LQM 996) on the mortality and behavior of Apis mellifera were evaluated by the acute oral toxicity test and the acute contact toxicity test. The oral lethal dose, 50% of the ethyl-carbamates was >145.24 µg per bee, and the oral lethal dose, 50% of propoxur was 0.072 µg per bee. Therefore, according to the OECD criteria, the ethyl-carbamates were classified as relatively nontoxic orally; meanwhile, propoxur was classified as highly toxic orally. In the contact test, lethal concentrations 50% of the ethyl-carbamates were 4.83 and 2.23 µg/cm2 for LQM 919 and LQM 996, respectively; therefore, they were at least 10-fold less lethal (p < 0.05) than propoxur (0.22 µg/cm2). The ethyl-carbamates reduced the activity of A. mellifera acetylcholinesterase by up to 30%. The ki and kd values of both ethyl-carbamates were lower (p < 0.05) than those of propoxur and indicated that they are weak inhibitors and with low affinity to A. mellifera acetylcholinesterase, which along with the absence of behavioral alterations suggests that the mortality caused by ethyl carbamates is not related to damage to the nervous system. According to these results, the evaluated ethyl-carbamates can be considered a low ecotoxic risk for A. mellifera.


Assuntos
Acetilcolinesterase/metabolismo , Abelhas/efeitos dos fármacos , Carbamatos/toxicidade , Poluentes Ambientais/toxicidade , Inseticidas/toxicidade , Animais , Abelhas/enzimologia , Comportamento Animal/efeitos dos fármacos , Exposição Dietética/efeitos adversos , Exposição Ambiental/efeitos adversos , Dose Letal Mediana , Testes de Toxicidade Aguda
12.
Ecotoxicol Environ Saf ; 188: 109908, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31706243

RESUMO

Pesticides have been extensively produced and used to help the agricultural production which leads to the contamination of the environment, soil, groundwater sources, and even foodstuffs. Fungicides carbendazim (CBZ) and chlorothalonil (Chl) are widely applied in agriculture and other aspects. CBZ or Chl have been reported to disrupt spermatogenesis and decrease semen quality. However, it is not understood the effects of pubertal exposure to low doses of CBZ and Chl together, and the underlying mechanisms. Therefore, the aim of current investigation was to explore the negative impacts of pubertal exposure to low doses of CBZ and Chl together on spermatogenesis and the role of epigenetic modifications in the process. We demonstrated that CBZ and Chl together synergize to decrease sperm motility in vitro (CBZ 1.0 + Chl 0.1, CBZ 10.0 + CHl 1.0, CBZ 100.0 + Chl 10 µM in incubation medium for 24 h) and sperm concentration and motility in vivo with ICR mice (CBZ 0.1 + Chl 0.1, CBZ 1.0 + CHl 1.0, CBZ 10.0 + Chl 10 mg/kg body weight; oral gavage for five weeks). CBZ + Chl significantly increase reactive oxygen species (ROS) and apoptosis by the increase in the protein level of caspase 8 in vitro. Moreover, CBZ + Chl synergized to disrupt mouse spermatogenesis with the disturbance in sperm production proteins and sperm proteins (VASA, A-Myb, STK31, AR, Acrosin). CBZ + Chl synergized to decrease the protein level of estrogen receptor alpha and the protein level of DNA methylation marker 5 mC in Leydig cells, and to increase the protein levels of histone methylation marker H3K9 and the methylation enzyme G9a in germ cells. Therefore, greater attention should be paid to the use of CBZ and Chl as pesticides to minimise their adverse impacts on spermatogenesis.


Assuntos
Benzimidazóis/toxicidade , Carbamatos/toxicidade , Epigênese Genética/efeitos dos fármacos , Fungicidas Industriais/toxicidade , Nitrilos/toxicidade , Espermatogênese/efeitos dos fármacos , Animais , Sinergismo Farmacológico , Receptor alfa de Estrogênio/metabolismo , Masculino , Metilação/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos ICR , Transdução de Sinais/efeitos dos fármacos , Espermatogênese/genética , Espermatozoides/efeitos dos fármacos
13.
Anal Chim Acta ; 1094: 113-121, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31761037

RESUMO

Alkaline phosphatase (ALP), an enzyme that catalyzes the hydrolysis of phosphate groups, is closely associated with many diseases, including bone disease, prostate cancer, and diabetes. Thus, new assays for ALP detection in live cells are needed to better understand its role in related biological processes. In this study, we constructed a novel near-infrared ratiometric fluorescent probe for detecting ALP activity with high sensitivity. The probe uses a new self-immolative mechanism that can achieve a rapid response (within 10 min) to ALP, detected as a spectral shift (from 580 to 650 nm). This method effectively avoids issues related to instrument variability, and the near-infrared fluorescence emission (650 nm) makes it more suitable for biological detection. Moreover, the high sensitivity (14-fold enhancement of the fluorescence ratio F650/F580) and low detection limit (0.89 U L-1) for ALP allows the probe to be adapted to complex biological environments. The assay was successfully performed using serum samples with a linear range of ALP of up to 150 U L-1. We used the developed probe to detect and image endogenous ALP in cells with satisfactory results, and we successfully used the probes to detect changes in endogenous ALP levels in zebrafish caused by drug-induced organ damage.


Assuntos
Fosfatase Alcalina/análise , Carbamatos/química , Corantes Fluorescentes/química , Organofosfatos/química , Acetaminofen/farmacologia , Animais , Carbamatos/síntese química , Carbamatos/toxicidade , Tetracloreto de Carbono/toxicidade , Bovinos , Teoria da Densidade Funcional , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/toxicidade , Células HeLa , Humanos , Limite de Detecção , Microscopia Confocal/métodos , Microscopia de Fluorescência/métodos , Modelos Químicos , Organofosfatos/síntese química , Organofosfatos/toxicidade , Peixe-Zebra
14.
Environ Geochem Health ; 42(6): 1767-1774, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31520318

RESUMO

Many amphibians use water bodies associated with agro-ecosystem for breeding and thus are exposed to multiple chemicals. Fejervarya limnocharis is a common frog occurring in rice paddy fields. The timings of pesticide application generally coincide with the tenure of the occurrence of tadpoles in shallow waters of paddy fields. Malathion and carbaryl are frequently used in rice paddy fields to control leafhoppers and rice bugs, respectively. Therefore, effects of mixtures of malathion and carbaryl insecticides on the survival of tadpoles and emergence of froglets of Fejervarya limnocharis were studied in the laboratory using combinations of three concentrations of carbaryl (0, 25, 50 µg l-1) with four concentrations of malathion (0, 100, 250, 500 µg l-1). Both malathion and carbaryl were found to be toxic to tadpoles. A reduction in tadpole survival and froglet emergence was recorded with increasing concentrations of carbaryl and malathion. We found significant interaction between carbaryl and malathion on tadpole survival and froglet emergence. Tadpoles exposed to combination of pesticides showed early emergence as froglets compared to control. The extent of toxicity and pesticide interactions are varied when mixed in different concentrations. The reduction in survival, froglet emergence and delay in emergence of metamorphs can occur in rice paddy field as both pesticides are used simultaneously. Therefore, combinations of pesticides may have significant negative effects on the frog population of agro-ecosystems, which requires further confirmation through appropriate field experiments.


Assuntos
Carbamatos/toxicidade , Malation/toxicidade , Praguicidas/toxicidade , Animais , Ecossistema , Inseticidas/toxicidade , Larva/efeitos dos fármacos , Ranidae
15.
Sci Rep ; 9(1): 19196, 2019 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-31844097

RESUMO

Securing food supply for a growing population is a major challenge and heavily relies on the use of agrochemicals to maximize crop yield. It is increasingly recognized, that some neonicotinoid insecticides have a negative impact on non-target organisms, including important pollinators such as the European honeybee Apis mellifera. Toxicity of neonicotinoids may be enhanced through simultaneous exposure with additional pesticides, which could help explain, in part, the global decline of honeybee colonies. Here we examined whether exposure effects of the neonicotinoid thiamethoxam on bee viability are enhanced by the commonly used fungicide carbendazim and the herbicide glyphosate. We also analysed alternative splicing changes upon pesticide exposure in the honeybee. In particular, we examined transcripts of three genes: (i) the stress sensor gene X box binding protein-1 (Xbp1), (ii) the Down Syndrome Cell Adhesion Molecule (Dscam) gene and iii) the embryonic lethal/abnormal visual system (elav) gene, which are important for neuronal function. Our results showed that acute thiamethoxam exposure is not enhanced by carbendazim, nor glyphosate. Toxicity of the compounds did not trigger stress-induced, alternative splicing in the analysed mRNAs, thereby leaving dormant a cellular response pathway to these man-made environmental perturbations.


Assuntos
Processamento Alternativo/efeitos dos fármacos , Abelhas/efeitos dos fármacos , Fungicidas Industriais/toxicidade , Herbicidas/toxicidade , RNA Mensageiro/genética , Tiametoxam/toxicidade , Animais , Abelhas/genética , Benzimidazóis/toxicidade , Carbamatos/toxicidade , Glicina/análogos & derivados , Glicina/toxicidade
16.
J Agric Food Chem ; 67(45): 12348-12356, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31638788

RESUMO

Carbosulfan is a carbamate insecticide that has been widely used in agriculture. However, studies showed that carbosulfan could be highly toxic to aquatic organisms. The metabolism of carbosulfan in adult zebrafish is still largely unexplored, and the metabolites in individual or in combination may pose a potential threat to zebrafish. In the present study, the bioaccumulation and metabolism of carbosulfan in zebrafish (Danio rerio) were assessed, and the main metabolites, including carbofuran and 3-hydroxycarbofuran, were determined. The toxicity of carbosulfan and its metabolites individually or in combination to zebrafish was also investigated. The bioaccumulation and metabolism experiment indicated that carbosulfan was not highly accumulated in zebrafish, with a bioaccumulation factor of 18 after being exposed to carbosulfan for 15 days, and the metabolism was fast, with a half-life of 1.63 d. The two main metabolites were relatively persistent, with half-lives of 3.33 and 5.68 d for carbofuran and 3-hydroxycarbofuran, respectively. The acute toxicity assay showed that carbofuran and 3-hydroxycarbofuran had 96-h LC50 values of 0.15 and 0.36 mg/L, showing them to be more toxic than carbosulfan (96-h LC50 = 0.53 mg/L). Combinations of binary or ternary mixtures of carbosulfan and its metabolites displayed coincident synergistic effects on acute toxicity, with additive index (AI) values of 1.9-14.3. In the livers and gills of zebrafish exposed to carbosulfan, carbofuran, and 3-hydroxycarbofuran, activities of catalase, superoxide dismutase, and glutathione-S-transferase were significantly changed in most cases, and the content of malondialdehyde was greatly increased, indicating that carbosulfan and its metabolites induced varying degrees of oxidative stress. The metabolites were more persistent and toxic to zebrafish and exhibit coincident synergistic effects in combination. These results can provide evidence for the potential risk of pesticides and highlight the importance of a systematic assessment for the combination of the precursor and its metabolites.


Assuntos
Carbamatos/metabolismo , Carbamatos/toxicidade , Inseticidas/metabolismo , Inseticidas/toxicidade , Peixe-Zebra/metabolismo , Animais , Carbofurano/análogos & derivados , Carbofurano/metabolismo , Carbofurano/toxicidade , Catalase , Glutationa Transferase/genética , Glutationa Transferase/metabolismo , Dose Letal Mediana , Estresse Oxidativo/efeitos dos fármacos , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Peixe-Zebra/genética , Peixe-Zebra/crescimento & desenvolvimento , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo
17.
Environ Sci Pollut Res Int ; 26(30): 31133-31141, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31463752

RESUMO

To improve crop yielding, a large amount of fungicides is continuously applied during the agricultural management, while the effects of fungicides residues on microbial processing of N in soil need further study. In the present study, two broad spectrum fungicides, chlorothalonil and carbendazim, were applied at the rates of 5, 10, and 50 mg of active ingredient (A.I.) per kg of dry soil combined with urea with 200 mg of N per kg of dry soil under laboratory conditions. The results showed that chlorothalonil obviously retarded the hydrolysis of urea, whereas carbendazim accelerated it in 4 days after the treatments (P < 0.05). Chlorothalonil reduced denitrification, nitrification, and N2O production (P < 0.05), but not for carbendazim. Further analysis on N-associated microbial communities showed chlorothalonil reduced nitrosomonas populations at the rates of 10 and 50 mg of A.I. per kg and autotrophic nitrifying bacterial populations at three application rates (P < 0.05), but Carbendazim decreased nitrosomonas populations only at the rate of 50 mg of A.I. per kg and also autotrophic nitrifying bacterial populations at three rates and heterotrophic nitrifying bacterial populations at the rates of 10 and 50 mg of A.I. per kg. The reasons for this difference were ascribed to arrest urea hydrolysis and impediment of denitrification and nitrification processes by chlorothalonil. In conclusion, to improve crop yielding, chlorothalonil might be more beneficial to conserve soil N by improving soil N fertility, compared with carbendazim.


Assuntos
Benzimidazóis/toxicidade , Carbamatos/toxicidade , Nitrilos/toxicidade , Nitrogênio/metabolismo , Microbiologia do Solo , Ureia/metabolismo , Bactérias/efeitos dos fármacos , Bactérias/metabolismo , Desnitrificação/efeitos dos fármacos , Fertilizantes , Fungicidas Industriais/toxicidade , Hidrólise , Nitrificação/efeitos dos fármacos , Nitrogênio/química , Solo/química , Ureia/química
18.
J Steroid Biochem Mol Biol ; 194: 105457, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31454535

RESUMO

Breast cancer is the most prevalent cancer in women affecting about 12% of world's female population. It is a multifactorial disease, mostly invasive in nature. Diosgenin and related compounds are potent antiproliferative agents. Carbamate derivatives have been synthesized at C26 of furostene ring after opening spiroketal bond (F-ring) of diosgenin. Compound 10 possessed significant antiproliferative activity against human breast cancer cells by arresting the population at G1 phase of cell division cycle and induced apoptosis. Induction of apoptosis was observed through the caspase signalling cascade by activating caspase-3. Moreover, carbamate 10 exhibited moderate antiinflammatory activity by decreasing the expression of cytokines, TNF-α and IL-6 in LPS-induced inflammation in primary macrophage cells. Furthermore, compound 10 significantly reduced Ehrlich ascites carcinoma significantly in mice. It was well tolerated and safe in acute oral toxicity in Swiss albino mice. The concomitant anticancer and antiinflammatory properties of carbamate 10 are important and thus, can further be optimized for a better anti-breast cancer candidate.


Assuntos
Anti-Inflamatórios , Antineoplásicos , Carbamatos , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/toxicidade , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antineoplásicos/toxicidade , Apoptose/efeitos dos fármacos , Carbamatos/farmacologia , Carbamatos/uso terapêutico , Carbamatos/toxicidade , Carcinoma de Ehrlich/tratamento farmacológico , Carcinoma de Ehrlich/patologia , Caspase 3/metabolismo , Caspase 9/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Feminino , Humanos , Interleucina-6/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Camundongos , Simulação de Acoplamento Molecular , Carga Tumoral/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo
19.
Environ Res ; 177: 108590, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31352300

RESUMO

BACKGROUND: Carbamate pesticides exposure have been linked with adverse health effects during developmental period. Based on 377 mother-child pairs from Sheyang Mini Birth Cohort Study, the present study aimed to assess carbofuranphenol exposure of three-year-old children and explore the associations between prenatal or postnatal carbofuranphenol exposures and neurodevelopmental indicators. METHODS: Urinary carbofuranphenol concentrations were measured by gas chromatography-tandem mass spectrometry. Neural developmental quotient (DQ) of children was evaluated using Gesell Developmental Schedules. Generalized linear models were used to examine the associations between carbofuranphenol concentrations and neurodevelopment. RESULTS: Geometric mean, geometric standard deviation, median, inter quartile range of postnatal urinary carbofuranphenol concentrations were 0.653 µg/L, 9.345 µg/L, 0.413 µg/L, 0.150-1.675 µg/L, respectively. Postnatal carbofuranphenol level showed negatively significant trend in language DQ [beta (ß) = -0.121; 95% confidence interval (95% CI): 0.212, -0.031; p value (p) = 0.008] and total average DQ (ß = -0.059, 95% CI: 0.115, -0.003; p = 0.035). Prenatal carbofuranphenol level showed negative correlations with children's adaptive DQ (ß = -0.755; 95% CI: 1.257, -0.254; p = 0.003), social DQ (ß = -0.341; 95% CI: 0.656, -0.027; p = 0.032) and total average DQ (ß = -0.349; 95% CI: 0.693, -0.005; p = 0.047). CONCLUSION: The results of the present study supposed children in agricultural region of China are widely exposed to carbamate pesticides, and both prenatal and postnatal exposure to carbamate pesticides may lead to neurodevelopmental effect.


Assuntos
Carbamatos/toxicidade , Desenvolvimento Infantil/efeitos dos fármacos , Exposição Ambiental/estatística & dados numéricos , Poluentes Ambientais/toxicidade , Transtornos do Neurodesenvolvimento/epidemiologia , Carbamatos/metabolismo , Criança , Pré-Escolar , China/epidemiologia , Estudos de Coortes , Poluentes Ambientais/metabolismo , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/epidemiologia
20.
Environ Toxicol Chem ; 38(8): 1692-1700, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31063226

RESUMO

Plasma cholinesterase activity is a biomarker sensitive to the effect of organophosphate and carbamate pesticides, and its enzymatic levels have been previously unknown for most of the wild birds analyzed in the present study. Our objectives were to establish plasma acetylcholinesterase levels in songbirds of 2 undisturbed sites in the central Monte Desert (Argentina). We also examined the influence on cholinesterase activity of age, sex, body condition, feeding and migratory habits, and species. One hundred and sixty-five wild birds belonging to 26 species were studied. The values obtained for acetylcholinesterase activity provide a good estimate of the normal values in free-living individuals of the species Zonotrichia capensis, Molothrus bonariensis, Passer domesticus, Diuca diuca, Poospiza ornata, Saltator aurantiirostris, Gryseotyrannus aurantioatrocristatus, and Columbina picui, with interspecies differences. The median enzymatic levels ± standard error of the mean ranged from 546.31 ± 17.97 µmol min-1 L-1 in P. domesticus to 3439.90 ± 173.92 µmol min-1 L-1 in Tyrannus melancholicus. No significant differences were detected between different sexes or ages. Birds that migrate (which are also insectivores) showed higher levels of cholinesterase than residents (mainly granivores). It is recommended that in cases of bird poisoning, plasma cholinesterase activity can be used as a diagnostic tool only if pre-exposure levels obtained in the same species are available, and ideally evaluated in individuals from the same biogeographical region. Environ Toxicol Chem 2019;38:1692-1700. © 2019 SETAC.


Assuntos
Acetilcolinesterase/sangue , Animais Selvagens/sangue , Monitoramento Ambiental/métodos , Poluentes Ambientais/toxicidade , Florestas , Aves Canoras/sangue , Animais , Argentina , Biomarcadores/sangue , Carbamatos/toxicidade , Feminino , Masculino , Organofosfatos/toxicidade , Praguicidas/toxicidade , Especificidade da Espécie
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