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1.
Toxicol Lett ; 322: 32-38, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31923464

RESUMO

Neonicotinoids (NNs), a widely used class of systemic pesticides, are regarded as exhibiting selective toxicity in insects. However, NNs are suspected of exerting adverse effects on mammals as well, including humans. To date, only adult male animal models have been subjected to general toxicity studies of NNs; fetuses have yet to be considered in this context. Here, we focused on the NN clothianidin (CLO) for the first quantitative LC-MS/MS analysis of maternal-to-fetal transfer and residual property of once-daily (single or multiple days), orally administered CLO and its metabolites in mice. The results revealed the presence of CLO and its five metabolites at approximately the same respective blood levels in both dams and fetuses. In the dams, CLO showed a peak value 1 h after administration, after which levels rapidly decreased at 3 and 6 h. In the fetuses of each group, levels of CLO were almost the same as those observed in the corresponding dams. The present results clearly demonstrated rapid passage of CLO through the placental barrier. However, metabolite-dependent differences observed in blood pharmacokinetics and residual levels. This is the first quantitative demonstration of the presence of CLO and its metabolites in fetal mouse blood.


Assuntos
Sangue Fetal/metabolismo , Guanidinas/sangue , Inseticidas/sangue , Troca Materno-Fetal , Neonicotinoides/sangue , Tiazóis/sangue , Animais , Biotransformação , Feminino , Guanidinas/administração & dosagem , Guanidinas/farmacocinética , Guanidinas/toxicidade , Inseticidas/administração & dosagem , Inseticidas/farmacocinética , Inseticidas/toxicidade , Exposição Materna , Camundongos Endogâmicos ICR , Neonicotinoides/administração & dosagem , Neonicotinoides/farmacocinética , Neonicotinoides/toxicidade , Gravidez , Medição de Risco , Tiazóis/administração & dosagem , Tiazóis/farmacocinética , Tiazóis/toxicidade , Toxicocinética
2.
Toxicol In Vitro ; 62: 104661, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31629900

RESUMO

Methylisothiazolinone (MIT) has been used in wide spectrum of fields due to its ability to inhibit microbial proliferation with low toxicity. Meanwhile, in Korea, the concern about the hazardous effects of MIT was amplified by the occurrence of patients that have humidifier disinfectant-associated pulmonary disease. However, the toxic mechanism for the pathological lesion is still unclear. In our previous study, we identified that cell viability decreased more rapidly in bronchial epithelial cells (BEAS-2B cells) compared to keratinocytes and liver epithelial cells under the same exposure condition. In this study we demonstrated that MIT (2, 4 and 8 µg/mL) induced dose-dependent cytotoxicity 24 h after exposure to BEAS-2B cells. Additionally, MIT impaired structure and function of intracellular organelles via oxidative stress, ultimately leading to apoptotic cell death. We also found notable activation of matrix metalloproteinases (MMPs) and clear aggregation of nucleolus proteins in MIT-treated cells. Furthermore, MIT increased secretion of proinflammatory cytokines (Interleukin (IL)-1ß, IL-6, and interferon-γ) and a chemokine (IL-8), and microarray and the KEGG pathway analysis proposed possible carcinogenesis following exposure to MIT. Taken together, we conclude that MIT induces apoptotic cell death and inflammatory response by activating MMPs in BEAS-2B cells. We also suggest that further study is necessary to clarify the possible carcinogenesis of MIT.


Assuntos
Anti-Infecciosos/toxicidade , Brônquios/citologia , Células Epiteliais/efeitos dos fármacos , Metaloproteinases da Matriz/metabolismo , Tiazóis/toxicidade , Apoptose/efeitos dos fármacos , Linhagem Celular , Citocinas/metabolismo , Células Epiteliais/metabolismo , Expressão Gênica/efeitos dos fármacos , Humanos , Organelas/efeitos dos fármacos , Organelas/ultraestrutura , Estresse Oxidativo/efeitos dos fármacos
3.
Chemosphere ; 240: 124862, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31550591

RESUMO

The photodegradation of benzisothiazolinone was studied in water under UV-Vis irradiation and led to fourteen photoproducts. Chemical structures of these compounds were elucidated using GC-MS, LCMS/MS, and FT-ICR-MS experiments. Based on the chemical structures determined and their appearance order, a photo induced-degradation mechanism of benzisothiazolinone has been proposed, which combines isomerization, oxidation, hydroxylation, hydrolysis, and elimination processes. In silico tests on mutagenicity, Fathead minnow LC50 and oral rat LD50 were carried out to estimate the toxicity of the photoproducts. Compared with experimental data, the calculated oral rat LD50 values were found to be the most relevant and thus used for toxicity estimation. The photoproducts including a phenolic or a sulfino group or both functions were found potentially more toxic than benzisothiazolinone.


Assuntos
Tiazóis/química , Poluentes Químicos da Água/química , Poluentes Químicos da Água/toxicidade , Administração Oral , Animais , Cromatografia Líquida , Simulação por Computador , Cyprinidae , Cromatografia Gasosa-Espectrometria de Massas , Cinética , Espectrometria de Massas , Fotólise , Ratos , Relação Estrutura-Atividade , Tiazóis/toxicidade , Testes de Toxicidade , Raios Ultravioleta , Poluentes Químicos da Água/administração & dosagem , Poluentes Químicos da Água/análise
4.
Ecotoxicol Environ Saf ; 188: 109880, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31711777

RESUMO

An increase in the area treated with the fungicide thifluzamide has triggered concerns for soil ecosystem service providers such as earthworms. Here, we assessed effects of thifluzamide on earthworm (Eisenia fetida) biomarker indicators of stress responses and reproduction following exposure to 0, 0.1, 1.0, and 10.0 mg of thifluzamide kg-1 soil for 7, 14, 21, and 28 d (biomarker indicators) and 30 d (reproduction). Growth and reproduction were inhibited by exposure to thifluzamide at 10.0 mg/kg, and the activities of succinate dehydrogenase (SDH) and respiratory chain complex II were inhibited by exposure to 1.0 and 10.0 mg/kg thifluzamide for the majority of the 28-d experiment. Reactive oxygen species (ROS) increased across all thifluzamide treatments, and the activities of superoxide dismutase (SOD) and glutathione-S-transferase (GST) tended to be inhibited by thifluzamide. Upon exposure to thifluzamide, the activities of catalase (CAT) and guaiacol peroxidase (POD) initially increased and then decreased. Increased levels of malondialdehyde (MDA) were detected only at seven days after exposure, and genotoxicity increased as the thifluzamide concentration increased. The results suggest that thifluzamide presents a potential risk to earthworms at the concentration of 10.0 mg/kg, and its use should be moderated to reduce damage to soil ecosystem function.


Assuntos
Anilidas/toxicidade , Oligoquetos/efeitos dos fármacos , Praguicidas/toxicidade , Poluentes do Solo/toxicidade , Tiazóis/toxicidade , Anilidas/análise , Animais , Antioxidantes/metabolismo , Dano ao DNA , Biomarcadores Ambientais/efeitos dos fármacos , Oligoquetos/crescimento & desenvolvimento , Oligoquetos/metabolismo , Oligoquetos/fisiologia , Estresse Oxidativo/efeitos dos fármacos , Praguicidas/análise , Reprodução/efeitos dos fármacos , Poluentes do Solo/análise , Tiazóis/análise
5.
Environ Toxicol ; 35(1): 27-36, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31498972

RESUMO

In 2011, a link between humidifier disinfectants and patients with idiopathic pulmonary fibrosis was identified in Korea, and Kathon was suggested as one of the causative agents. In this study, Kathon induced apoptotic cell death along with membrane damage at 24 h post-exposure. Additionally, on day 14 after a single instillation with Kathon, the total number of pulmonary cells and the levels of TNF-α, IL-5, IL-13, MIP-1α, and MCP-1α clearly increased in the lung of mice. The proportion of natural killer cells and eosinophils were significantly elevated in the spleen and the bloodstream, respectively, and the level of immunoglobulin (Ig) A, but not IgG, IgM, and IgE, dose-dependently increased. Therefore, we suggest that inhaled Kathon may induce eosinophilia-mediated disease in the lung by disrupting homeostasis of pulmonary surfactants. Considering that eosinophilia is closely related to cancer and fibrosis, further studies are needed to understand the relationship between them.


Assuntos
Desinfetantes/toxicidade , Eosinofilia/induzido quimicamente , Pulmão/efeitos dos fármacos , Surfactantes Pulmonares/metabolismo , Tiazóis/toxicidade , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular , Citocinas/imunologia , Eosinofilia/sangue , Eosinofilia/imunologia , Eosinófilos/citologia , Humanos , Imunoglobulina A/sangue , Exposição por Inalação/efeitos adversos , Pulmão/imunologia , Pulmão/metabolismo , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos ICR
6.
Aquat Toxicol ; 217: 105335, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31706209

RESUMO

One of the categories of environmental contaminants possibly contributing to declining sockeye salmon (Oncorhynchus nerka) in the Fraser River, British Columbia, Canada is pesticides. In this 4-month study, the effects of environmentally relevant concentrations of a waterborne neonicotinoid, clothianidin (0.15, 1.5, 15 and 150 µg/L), on embryonic, alevin and early swim-up fry sockeye salmon derived from four unique genetic crosses of the Pitt River, BC stock were investigated. There were no significant effects of clothianidin on survival, hatching, growth or deformities, although genetic variation significantly affected these endpoints. Clothianidin caused a significant 4.7-fold increase in whole body 17ß-estradiol levels in swim-up fry after exposure to 0.15 µg/L, but no effects were observed on testosterone levels. In addition, hepatic expression of the gene encoding glucocorticoid receptor 2 was also impacted at the highest concentration of clothianidin tested, and was found to be ∼4-fold lower compared to the sockeye reared in control water. These results indicate additional examination of clothianidin and its effects on salmonid gonad development and the reproductive and stress endocrine axes in general, is warranted.


Assuntos
Embrião não Mamífero/efeitos dos fármacos , Desenvolvimento Embrionário/efeitos dos fármacos , Guanidinas/toxicidade , Neonicotinoides/toxicidade , Rios/química , Salmão/crescimento & desenvolvimento , Tiazóis/toxicidade , Poluentes Químicos da Água/toxicidade , Migração Animal/efeitos dos fármacos , Animais , Colúmbia Britânica , Sistema Endócrino/efeitos dos fármacos , Sistema Endócrino/crescimento & desenvolvimento , Estradiol/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Fígado/metabolismo , Receptores de Glucocorticoides/genética , Reprodução/efeitos dos fármacos , Salmão/metabolismo , Natação
7.
Bull Environ Contam Toxicol ; 103(5): 717-722, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31492972

RESUMO

Neonicotinoid insecticides are highly water soluble with relatively long half-lives, which allows them to move into and persist in aquatic ecosystems. However, little is known of the impacts of neonicotinoids on non-target vertebrates, especially at sublethal concentrations. We evaluated the effects of the neonicotinoid clothianidin on the behavior of southern leopard frog tadpoles (Rana sphenocephala) after a 96-h exposure at 6 concentrations, including 0 (control), 0.375, 0.75, 1.5, 3.0, 6.0 µg/L. We quantified total displacement, mean velocity, maximum velocity, and time spent moving of tadpoles for 1 h post-exposure. Total displacement and mean velocity of tadpoles decreased with clothianidin exposure. Maximum velocity decreased linearly with concentration, but there was no relationship between time spent moving and clothianidin concentration. Our results suggest exposure to clothianidin at sublethal concentrations can affect movement behavior of non-target organisms such as tadpoles.


Assuntos
Guanidinas/toxicidade , Inseticidas/toxicidade , Larva/efeitos dos fármacos , Neonicotinoides/toxicidade , Tiazóis/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Comportamento Animal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ecossistema , Guanidinas/análise , Inseticidas/análise , Neonicotinoides/análise , Rana pipiens , Tiazóis/análise , Poluentes Químicos da Água/análise
8.
Analyst ; 144(16): 4750-4756, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31282915

RESUMO

Cancer is a global health issue and a leading cause of death. The discrimination of cancer cells from normal cells is of significant importance for the early diagnosis of cancers. As one of the useful biomarkers for developing cancer diagnosis and chemotherapy resistance systems, biothiols not only play an essential role in physiological and pathological processes but also exhibit cytoprotective effects in the susceptibility to carcinogenesis. It would be highly desirable to explore near-infrared biothiol-specific fluorescent probes for cancer diagnosis with outstanding specificity. In this study, a novel near-infrared fluorescent probe BPO-THAZ decorated with thiazole as a recognition site was presented for sensitive and selective detection of endogenous biothiols. BPO-THAZ can be used to not only evaluate the biothiol level in living HeLa cells upon treatment with H2O2 or anti-cancer drugs but also assess endogenous biothiols in stem cells. Furthermore, BPO-THAZ was successfully utilized to discriminate cancer cells from normal cells showing great promise for cancer diagnosis.


Assuntos
Corantes Fluorescentes/química , Compostos de Sulfidrila/análise , Tiazóis/química , Animais , Biomarcadores Tumorais/análise , Linhagem Celular Tumoral , Células-Tronco Embrionárias , Fluoresceínas/síntese química , Fluoresceínas/química , Fluoresceínas/toxicidade , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/toxicidade , Humanos , Limite de Detecção , Camundongos , Microscopia Confocal/métodos , Microscopia de Fluorescência/métodos , Células NIH 3T3 , Células-Tronco Pluripotentes , Tiazóis/síntese química , Tiazóis/toxicidade
9.
Chemosphere ; 235: 280-287, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31260868

RESUMO

Thifluzamide as a fungicide is toxic to brain of zebrafish embryos. Brain can regulate biological rhythms. To clarify whether thifluzamide would influence circadian rhythms, zebrafish embryos were treated with thifluzamide (0, 0.19, 1.90 and 2.85 mg/L) for 4 days. Exposure to thifluzamide induced pronounced changes in embryo brain and melatonin levels. The mRNA levels of genes related to circadian rhythms were apparently altered. Among these, the transcripts of cry1ba and clock1 were extremely correlated with exposure concentrations. Importantly, the content of cry1 showed no apparent changes, but the clock level was dramatically increased. Moreover, consistent with the inhibition of development and behavior, the levels of GH and DA were significantly inhibited. In addition, the expression levels of genes related to development, behavior and reproduction were significantly changed by thifluzamide. Therefore, we speculated that circadian disruption due to thifluzamide exposure were primarily attributed to increases in expression of clock1a and contents of clock, which might be at least in part responsible for abnormal development and behavior of zebrafish. In addition, our research will provide important insights into the grouped assessment of SDHI pesticides in future.


Assuntos
Anilidas/toxicidade , Ritmo Circadiano/efeitos dos fármacos , Tiazóis/toxicidade , Peixe-Zebra/fisiologia , Animais , Encéfalo/efeitos dos fármacos , Ritmo Circadiano/genética , Proteínas de Ligação a DNA/metabolismo , Relação Dose-Resposta a Droga , Embrião não Mamífero , Fungicidas Industriais/toxicidade , Melatonina/metabolismo , RNA Mensageiro/metabolismo , Peixe-Zebra/embriologia , Proteínas de Peixe-Zebra/metabolismo
10.
Chemosphere ; 232: 171-179, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31154177

RESUMO

Tricyclazole is widely used in agriculture as a pesticide, but its toxicity in vertebrates is currently poorly evaluated. In this study, we used zebrafish to assess the toxicity of tricyclazole. We found that tricyclazole induces liver damage, or hepatotoxicity, in zebrafish, during both development and adulthood. In embryos, we found that tricyclazole affected the liver development rather than other endodermal tissues such as gut and pancreas. In both embryos and adult zebrafish livers, tricyclazole disrupted the relationship between oxidant and antioxidant system and resulted in reactive oxygen species (ROS) overload. Meanwhile, it triggered hepatocyte apoptosis and disturbed carbohydrate/lipid metabolism and energy demand systems. These results suggested that tricyclazole could cause severe consequences for vertebrate hepatic development and function.


Assuntos
Tiazóis/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Antioxidantes/metabolismo , Apoptose , Doença Hepática Induzida por Substâncias e Drogas , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Peixe-Zebra/metabolismo
11.
Int J Toxicol ; 38(1_suppl): 70S-84S, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31170842

RESUMO

The Cosmetic Ingredient Review Expert Panel (Panel) reviewed the safety of methylisothiazolinone (MI), which functions as a preservative. The Panel reviewed relevant animal and human data provided in this safety assessment and in a previously published safety assessment of MI and concluded that MI is safe for use in rinse-off cosmetic products at concentrations up to 100 ppm and safe in leave-on cosmetic products when they are formulated to be nonsensitizing, which may be determined based on a quantitative risk assessment.


Assuntos
Cosméticos/toxicidade , Tiazóis/toxicidade , Animais , Qualidade de Produtos para o Consumidor , Cosméticos/química , Cosméticos/farmacocinética , Humanos , Medição de Risco , Tiazóis/química , Tiazóis/farmacocinética
12.
Eur J Med Chem ; 177: 153-170, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31132531

RESUMO

The eukaryotic initiation factor 4E (eIF4E) is an emerging anticancer drug target for specific anticancer therapy as a promising approach to overcome drug resistance and promote chemotherapy antitumor efficacy. A series of bromophenol-thiazolylhydrazone hybrids were designed, synthesized and evaluated for their antitumor activities. Among of them, the most potent compound 3e (EGPI-1) could inhibit the eIF4E/eIF4G interaction. Further mechanism study demonstrated EGPI-1 played an antitumor role in multiple modes of action including regulating the activity of eIF4E by inhibiting the phosphorylation of eIF4E and 4EBP1, disrupting mitochondrial function through the mTOR/4EBP1 signaling pathway, and inducing autophagy, apoptosis and ROS generation. Moreover, EGPI-1 showed good safety and favorable pharmacokinetic properties in vivo. These observations demonstrate that EGPI-1 may serve as an excellent lead compound for the development of new anticancer drugs that target the eIF4E/eIF4G interface and as a chemical genetic probe to investigate the role of the eIF4E in biological processes and human diseases.


Assuntos
Antineoplásicos/farmacologia , Fator de Iniciação 4E em Eucariotos/antagonistas & inibidores , Fator de Iniciação 4G em Eucariotos/antagonistas & inibidores , Hidrazonas/farmacologia , Tiazóis/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/farmacocinética , Antineoplásicos/toxicidade , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Sítios de Ligação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Desenho de Fármacos , Fator de Iniciação 4E em Eucariotos/química , Fator de Iniciação 4E em Eucariotos/metabolismo , Fator de Iniciação 4G em Eucariotos/metabolismo , Feminino , Células Endoteliais da Veia Umbilical Humana , Humanos , Hidrazonas/síntese química , Hidrazonas/farmacocinética , Hidrazonas/toxicidade , Masculino , Camundongos , Simulação de Acoplamento Molecular , Fosforilação , Ligação Proteica , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Tiazóis/síntese química , Tiazóis/farmacocinética , Tiazóis/toxicidade , Ensaios Antitumorais Modelo de Xenoenxerto
13.
Artigo em Inglês | MEDLINE | ID: mdl-31055069

RESUMO

Sea-Nine™ 211 is an emerging biocide that has an adverse impact on aquatic environments. In this study, the marine polychaete Perinereis aibuhitensis was exposed to Sea-Nine (0.1, 1, and 10 µg L-1), and acute toxicity and biochemical responses such as changes in the intracellular contents of malondialdehyde (MDA) and glutathione (GSH) and enzymatic activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST), and acetylcholinesterase (AChE) were evaluated over a period of 14 d. Determined median lethal doses, LC50 were 268 µg L-1, 142 µg L-1, and 55 µg L-1 at 24 h, 96 h, and 14 d, respectively. The MDA content increased significantly in a dose- and time-dependent manner, indicative of lipid peroxidation-related oxidative damage. Significantly higher intracellular GSH levels and antioxidant defense-related enzyme (CAT, SOD, GPx, GR, and GST) activities were observed after exposure to 10 µg L-1 Sea-Nine. In contrast, Sea-Nine treatment significantly reduced AChE activity at the highest concentration of Sea-Nine used (10 µg L-1). Taken together, these results indicate that sublethal concentrations of Sea-Nine are toxic to marine polychaetes through potential lipid peroxidation, induction of oxidative stress, and modulation of the cholinergic system. Our results can contribute to biomonitoring of aquatic environments and ecotoxicological research through the measurements of polychaete cellular defenses against waterborne biocides.


Assuntos
Desinfetantes/toxicidade , Poliquetos/efeitos dos fármacos , Tiazóis/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Antioxidantes/metabolismo , Relação Dose-Resposta a Droga , Esquema de Medicação , Glutationa/metabolismo , Malondialdeído/metabolismo , Tiazóis/administração & dosagem , Poluentes Químicos da Água/administração & dosagem
14.
Ecotoxicol Environ Saf ; 180: 23-32, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31059904

RESUMO

The use of alternative biocides has increased due to their economic and ecological relevance. Although data regarding the toxicity of commercial alternative biocides in marine organisms are accumulating, little is known about their toxic pathways or mechanisms. To compare the toxic effects of commercial alternative biocides on non-target pelagic fish (flounder) embryos, we investigated the adverse effects of developmental malformation and transcriptional changes. Three biocides including Diuron, Irgarol 1051® and Sea-Nine 211® produced a largely overlapping suite of developmental malformations, including tail-fin fold defects and dorsal body axis curvature. In our test, the potencies of these biocides were ranked in the following order with respect to malformation and mortalities: Sea-Nine 211®â€¯> Irgarol 1051®â€¯> Diuron. Consistent with the toxicity rankings, the expression of genes related to heart formation was greater in embryonic flounder exposed to Sea-Nine 211® than in those exposed to Irgarol 1051® or Diuron, while expression of genes related to fin malformation was greater in the Irgarol 1051® exposure group. In analyses of differential gene expression (DEG) profiles (fold change of genes with a cutoff P < 0.05) by high-throughput sequencing (RNA-seq), genes associated with nervous system development, transmembrane transport activity, and muscle cell development were significantly changed commonly. Embryos exposed to Diuron showed changes related to cellular protein localization, whereas genes associated with immune system processes were up-regulated significantly in embryos exposed to Irgarol 1051®. Genes related to actin filament organization and embryonic morphogenesis were up-regulated in embryos exposed to Sea-Nine 211®. Overall, our study provides a better understanding of the overlapping and unique developmental toxic effects of three commercial booster biocides through transcriptomic analyses in a non-target species, embryonic flounder.


Assuntos
Desinfetantes/toxicidade , Embrião não Mamífero/efeitos dos fármacos , Peixes/crescimento & desenvolvimento , Poluentes Químicos da Água/toxicidade , Animais , Incrustação Biológica/prevenção & controle , Diurona/toxicidade , Desenvolvimento Embrionário/efeitos dos fármacos , Tiazóis/toxicidade , Triazinas/toxicidade
15.
Environ Pollut ; 251: 708-716, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31108304

RESUMO

DCOIT (4,5-dichloro-2-n-octyl-4-isothiazolin-3-one) is the main component of SeaNine-211, a new antifouling agent that replaces tributyltin to prevent the growth of undesirable organisms on ships. There have been some studies on the toxicity of DCOIT, but the mechanism of DCOIT's toxicity to crustaceans still requires elucidation. This study examined the chronic toxicity (4 weeks) of 0, 3, 15, and 30 µg/L DCOIT to the Pacific white shrimp (Litopenaeus vannamei) from the aspects of growth and physiological and histological changes in the hepatopancreas and gills. A transcriptomic analysis was performed on the hepatopancreas to reveal the underlying mechanism of DCOIT in shrimp. The exposure to 30 µg/L DCOIT significantly reduced the survival and weight gain of L. vannamei. High Na+/K+-ATPase activity and melanin deposition were found in the gills after 4 weeks of 15 µg/L or 30 µg/L DCOIT exposure. The highest concentration of DCOIT (30 µg/L) induced changes in hepatopancreatic morphology and metabolism, including high anaerobic respiration and the accumulation of triglycerides. Compared with the exposure to 3 µg/L DCOIT, shrimp exposed to 15 µg/L DCOIT showed more differentially expressed genes (DEGs) than those in the control, and these DEGs were involved in biological processes such as starch and sucrose metabolism and choline metabolism in cancer. The findings of this study indicate that L. vannamei is sensitive to the antifouling agent DCOIT and that DCOIT can induce altered gene expression at a concentration of 15 µg/L and can interfere with shrimp metabolism, growth and survival at 30 µg/L.


Assuntos
Penaeidae/efeitos dos fármacos , Tiazóis/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Relação Dose-Resposta a Droga , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/efeitos dos fármacos , Brânquias/efeitos dos fármacos , Brânquias/metabolismo , Hepatopâncreas/efeitos dos fármacos , Hepatopâncreas/metabolismo , Penaeidae/crescimento & desenvolvimento , Penaeidae/metabolismo , Ganho de Peso/efeitos dos fármacos
16.
Ecotoxicol Environ Saf ; 180: 139-145, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31082577

RESUMO

Neonicotinoids act as agonists on the nicotinic Acetylcholine receptor (nAChR) in insect brains, an essential molecular component of central brain structures involved in learning and memory formation. Sublethal doses might, therefore, impair neural processes necessary for adaptive experience dependent behaviour and thus reduce the fitness of pollinating insects on the individual and community level. First, the question was addressed whether clothianidin has an aversive taste for honey bees and concluded with both a laboratory and a semi-field experiment that bees are unable to distinguish between control and contaminated sucrose solutions. In the laboratory, proboscis extension response conditioning was performed with forager bees exposed to different concentrations of clothianidin (0.1, 0.3 and 0.8 ng/bee) before learning, after learning during memory consolidation, and just before memory retention. These tests at different timings allowed uncovering an impairment of the consolidation and retrieval of memory due to the exposure to clothianidin. It was concluded that an acute exposure to clothianidin has an adverse effect on memory processing in honey bees.


Assuntos
Abelhas/fisiologia , Exposição Ambiental/efeitos adversos , Guanidinas/toxicidade , Inseticidas/toxicidade , Memória/efeitos dos fármacos , Neonicotinoides/toxicidade , Tiazóis/toxicidade , Animais , Comportamento Alimentar/efeitos dos fármacos , Aprendizagem/efeitos dos fármacos , Aprendizagem/fisiologia , Memória/fisiologia , Análise de Sobrevida , Percepção Gustatória
18.
Pestic Biochem Physiol ; 154: 39-45, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30765055

RESUMO

The brown planthopper, Nilaparvata lugens (Stål), is one of the most economically important rice pests in Asia and has become resistant to various kinds of insecticides, including neonicotinoid insecticides. In this study, an N. lugens clothianidin-resistant (CLR) strain and a susceptible (CLS) strain were established, and the potential resistance mechanisms of N. lugens to clothianidin were elucidated. The cross-resistance studies showed that the clothianidin-resistant strain exhibited cross-resistance to most neonicotinoid insecticides, especially nitenpyram (99.19-fold) and dinotefuran (77.68-fold), while there was no cross-resistance to chlorpyrifos (1.79-fold). The synergism assays and the activities of the detoxification enzymes were performed, and we found that a cytochrome P450 conferred the clothianidin resistance. Two P450 genes (CYP6ER1 and CYP6AY1) were found to be significantly overexpressed in the CLR strain compared with the CLS strain based on qRT-PCR. In addition, the knockdown of CYP6ER1 by RNA interference dramatically increased the toxicity of clothianidin against N. lugens. These data demonstrated that the overexpression of CYP6ER1 could contribute to clothianidin resistance in N. lugens. Our findings will help to improve the design of effective resistance management strategies to control brown planthoppers.


Assuntos
Família 6 do Citocromo P450/genética , Guanidinas/toxicidade , Hemípteros/efeitos dos fármacos , Proteínas de Insetos/genética , Resistência a Inseticidas/genética , Inseticidas/toxicidade , Neonicotinoides/toxicidade , Ninfa/efeitos dos fármacos , Tiazóis/toxicidade , Animais , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Hemípteros/fisiologia , Ninfa/fisiologia
19.
Andrologia ; 51(5): e13241, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30706522

RESUMO

Mirabegron is a selective beta3-adrenoceptor (ß3 -AR) agonist, which is commonly used for the treatment of overactive bladder. This medicine is associated with atrophy of reproductive organs in rats. However, no study has examined the detailed action and mechanism of its toxicity in reproductive cells. In this study, we examined the effect of mirabegron on primary cultured rat Sertoli cells. Firstly, RT-PCR and immunocytochemistry revealed that ß3 -AR was present in rat Sertoli cells. Then, primary cultured rat Sertoli cells were treated with mirabegron. Quantitative real-time PCR revealed that mirabegron treatment induced a significant increase in claudin-11 mRNA, which is crucial for spermatogenesis. Western blot analysis also showed that mirabegron treatment significantly activated p44/42 mitogen-activated protein kinase (MAPK). After additional treatment with U0126, a specific noncompetitive inhibitor of mitogen-activated protein kinase kinase (MAPKK), the upregulation of claudin-11 mRNA induced by mirabegron was reduced. At the same time, immunocytochemistry showed mirabegron treatment disturbed claudin-11 localisation to tight junction, which was recovered when treated with mirabegron in the presence of U0126. These results suggest that mirabegron treatment is associated with assembly of the blood-testis barrier through p44/42 MAPK pathway. These findings could explain one of the underlying mechanisms of reproductive toxicity induced by mirabegron.


Assuntos
Acetanilidas/toxicidade , Agonistas de Receptores Adrenérgicos beta 3/toxicidade , Barreira Hematotesticular/efeitos dos fármacos , Células de Sertoli/efeitos dos fármacos , Tiazóis/toxicidade , Junções Íntimas/efeitos dos fármacos , Animais , Butadienos/farmacologia , Células Cultivadas , Claudinas/metabolismo , Masculino , Proteína Quinase 1 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Nitrilos/farmacologia , Cultura Primária de Células , Ratos , Ratos Sprague-Dawley , Células de Sertoli/citologia , Células de Sertoli/metabolismo , Transdução de Sinais/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Junções Íntimas/metabolismo
20.
J Environ Sci Health B ; 54(4): 326-335, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30773126

RESUMO

A modified quick, easy, cheap, effective, rugged and safe (QuEChERS) method was developed for the determination of thiamethoxam and its metabolite clothianidin in citrus (including the whole citrus, peel and pulp) and soil samples by liquid chromatography-tandem mass spectrometry. The sample was extracted with acetonitrile and purified with octadecylsilane. The detection limits of both compounds were 0.0001-0.0002 mg kg-1, while the limit of quantification of thiamethoxam was 0.002 mg kg-1 and the limit of quantitation of metabolites was 0.001 mg kg-1. The recovery was 70.37%-109.76%, with inter-day relative standard deviations (RSD) (n = 15) values ≤9.46% for the two compounds in the four matrices. The degradation curve of thiamethoxam in whole citrus and soil was plotted using the first-order kinetic model. The half-life of the whole citrus was 1.9-6.2 days, and the half-life of the soil was 3.9-4.2 days. The terminal residue of thiamethoxam (the sum of thiamethoxam and clothianidin, expressed as thiamethoxam) was found to be concentrated on the peel. The final residual amount of thiamethoxam in the edible portion (pulp) was less than 0.061 mg kg-1. The risk quotient values were all below 1, indicating that thiamethoxam as a citrus insecticide does not pose a health risk to humans at the recommended dosage.


Assuntos
Citrus/química , Contaminação de Alimentos/análise , Guanidinas/análise , Neonicotinoides/análise , Poluentes do Solo/análise , Tiametoxam/análise , Tiazóis/análise , China , Cromatografia Líquida/métodos , Exposição Dietética/análise , Guanidinas/toxicidade , Meia-Vida , Humanos , Inseticidas/análise , Limite de Detecção , Neonicotinoides/toxicidade , Medição de Risco , Espectrometria de Massas em Tandem/métodos , Tiametoxam/toxicidade , Tiazóis/toxicidade
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