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1.
Mutat Res ; 850-851: 503148, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32247557

RESUMO

Norharman exists in cigarette smoke and cooked foods and is non-mutagenic among Salmonella strains but mutagenic to S. typhimurium TA98 and YG1024 in the presence of S9 mix and aniline and o-toluidine. Co-mutagenesis of ß-carbolines and aniline and o-toluidine occurs through the formation of novel mutagenic aminophenyl-ß-carboline derivatives including 9-(4'-aminophenyl)-9H-pyrido[3,4-b]indole [aminophenylnorharman] (APNH)] and 9-(4'- amino-3'-methylphenyl)-9H-pyrido[3,4-b]indole [aminomethylphenylnorharman] (AMPNH)]. Since humans are often simultaneously exposed to ß-carbolines and aniline and o-toluidine, their effects on humans should be clarified. The most potent of these, APNH, induced both point mutations and small deletions in the liver and colon of gpt delta transgenic mice. Major APNH-induced mutations in the liver occurred at a G:C base pair, suggesting that APNH-DNA adducts (dG-C8-APNH) are potentially involved in these mutations. Furthermore, APNH induced hepatic and colon tumors harboring K-ras, ß-catenin, and Apc mutations in F344 rats, with high incidence. Mutations at G:C base pairs were predominant, similar to those in the in vivo mutation assay using gpt delta mice. Moreover, APNH detected in human urine samples obtained from both healthy volunteers on a normal diet and inpatients receiving parenteral alimentation; therefore, APNH can be considered an endogenous carcinogen contributing to tumorigenesis. Exposure levels of these aminophenyl-ß-carboline derivatives may be lower than those of carcinogenic heterocyclic amines (HCAs) including 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx); however, their health risks in terms of tumorigenesis may be comparable owing to stronger genotoxic effects of APNH rather than HCAs. This review summarized APNH mutagenicity/carcinogenicity, and its in vivo formation. Moreover, the effect on tumorigenesis in humans also discussed.


Assuntos
Carbolinas/química , Indóis/toxicidade , Mutagênese/efeitos dos fármacos , Piridinas/toxicidade , Toluidinas/química , Compostos de Anilina/toxicidade , Animais , Carbolinas/toxicidade , Colo/efeitos dos fármacos , Humanos , Fígado/efeitos dos fármacos , Camundongos , Camundongos Transgênicos , Mutação Puntual/efeitos dos fármacos , Toluidinas/toxicidade
2.
Arch Environ Contam Toxicol ; 78(4): 545-554, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31915850

RESUMO

Chemicals pollution in the environment has attracted attention all over the world, and the toxicity prediction of chemical pollutants has become quite important. In this paper, we introduce a simple approach to predict the toxicity of some chemical components, in which the Tchebichef image moment (TM) method was employed to extract useful chemical information from the images of molecular structures to establish quantitative structure-activity relationship (QSAR) prediction models. The proposed approach was applied to predict the toxicity of anilines and phenols for the aquatic organisms of P. subcapitata and V. fischeri, in which the obtained TMs were defined as the independent variables, while the biological toxicity (pEC50) was regarded to be the dependent variable. Then, the predictive models were established by stepwise regression, respectively. The obtained squared correlation coefficients of leave-one-out cross-validation (Q2) for training sets and the predictive squared correlation coefficients (Rp2) for test sets of the two groups of data were higher than 0.79 and 0.75, respectively, which indicated that the obtained models possessed satisfactory accuracy and reliability. Compared with several reported methods, the proposed approach was more convenient and has a higher predictive capability. Our study provides another perspective in QSAR research.


Assuntos
Compostos de Anilina/toxicidade , Organismos Aquáticos/efeitos dos fármacos , Modelos Teóricos , Fenóis/toxicidade , Poluentes Químicos da Água/toxicidade , Aliivibrio fischeri/efeitos dos fármacos , Compostos de Anilina/química , Clorófitas/efeitos dos fármacos , Fenóis/química , Valor Preditivo dos Testes , Relação Quantitativa Estrutura-Atividade , Reprodutibilidade dos Testes , Poluentes Químicos da Água/química
3.
Chemosphere ; 240: 124945, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31726594

RESUMO

In this study, the effect of high concentration of Mn2+ on the aerobic granular sludge (AGS) systems for aniline wastewater treatment was systematically investigated in terms of AGS formation and pollutant removal efficiency. Two parallel sequencing batch reactors were operated to treat the aniline-rich wastewater with and without 20 mg L-1 of Mn2+. In the presence of Mn2+, the time to granulation was prolonged from 23 d to 30 d due to the toxicity of the high concentration of Mn2+. However, the mature granules with Mn2+ produced more protein and polysaccharides, and had a larger size (870 µm) than that without Mn2+ (740 µm). The extracellular polymeric substances of the granules in the two reactors had similar protein compositions, but some functional groups increased with Mn2+. The reactors showed high overall removal efficiency of chemical oxygen demand, NH4+-N, and total nitrogen with average concentrations below 40, 1.0, and 19 mg L-1, respectively, in the effluents. In one typical operating cycle, however, Mn2+ retarded nitrification and the degradation of aniline, while promoted denitrification. The microbial community analysis revealed that the growth of Terrisporobacter, Pseudomonas, and many other bacteria responsible for aniline degradation was inhibited by Mn2+, and so were the strains involved in nitrification. In contrast, Mn2+ facilitated the growth of denitrifying bacteria.


Assuntos
Compostos de Anilina/toxicidade , Manganês/toxicidade , Eliminação de Resíduos Líquidos , Poluentes Químicos da Água/toxicidade , Aerobiose , Compostos de Anilina/metabolismo , Bactérias/metabolismo , Análise da Demanda Biológica de Oxigênio , Reatores Biológicos/microbiologia , Desnitrificação , Microbiota , Nitrificação , Nitrogênio/análise , Esgotos/química , Águas Residuárias/química
4.
Aquat Toxicol ; 217: 105345, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31715477

RESUMO

Lethal and sublethal effects of trinitrotoluene (TNT) and its degradation products 2-amino-4,6-dinitrotoluene (2-ADNT) and 4-amino-2,6-dinitrotoluene (4-ADNT) to zebrafish embryos (Danio rerio) were investigated in a 120 h exposure scenario. Lethal concentrations (LC50) were 4.5 mg/l for TNT, 13.4 mg/l for 2-ADNT and 14.4 mg/l for 4-ADNT. Embryos exposed to 2-ADNT or 4-ADNT revealed a high proportion of chorda deformations among the surviving individuals. Genotoxicity of the nitroaromatic compounds in zebrafish embryos was investigated by comet assay isolating cells from whole embryos after 48 h in vivo exposure. Significant genotoxicity was induced by all three compounds tested, in comparison to the corresponding controls at 0.1 mg/l and 1.0 mg/l as lowest tested concentrations. The genotoxicity caused by TNT was about three to four times higher than that of 2-ADNT and 4-ADNT. To our knowledge, this is the first study demonstrating the genotoxicity of TNT in fish embryos by in vivo exposure. The results are discussed in the context of dumped munition in the marine environment.


Assuntos
Dano ao DNA , Embrião não Mamífero/efeitos dos fármacos , Mutagênicos/toxicidade , Trinitrotolueno/toxicidade , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/crescimento & desenvolvimento , Compostos de Anilina/toxicidade , Animais , Peixe-Zebra/genética
5.
Chem Asian J ; 14(23): 4160-4163, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31657112

RESUMO

Multifunctional nanoparticles were simply synthesized by mixing a TICT+AIE featured molecule (TPAPP-CHO) with PBS solution. The fluorescent (FL) dots entered the cells via energy-related endocytosis and were located in lysosome emitting green FL. This indicated that the nanoparticles were dissociated in the lysosome. Moreover, the synthesized nanoparticles (NPs) demonstrate potent cytotoxicity against human U87 glioblastoma cells by inducing cell apoptosis via triggering intracellular ROS overproduction.


Assuntos
Compostos de Anilina/toxicidade , Apoptose/efeitos dos fármacos , Benzaldeídos/toxicidade , Corantes Fluorescentes/química , Pontos Quânticos/toxicidade , Tiadiazóis/toxicidade , Compostos de Anilina/química , Compostos de Anilina/uso terapêutico , Benzaldeídos/química , Benzaldeídos/uso terapêutico , Linhagem Celular Tumoral , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Pontos Quânticos/química , Pontos Quânticos/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Tiadiazóis/química , Tiadiazóis/uso terapêutico
6.
Aquat Toxicol ; 215: 105282, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31509759

RESUMO

Aquatic ecosystems are now chronically polluted by a cocktail of many chemical substances. There is now clear evidence of associations between exposure to pollutants and greater susceptibility to pathogens. The aim of the present study was to characterize the defense capacities of rainbow trout (Oncorhynchus mykiss), chronically exposed to pendimethalin (PD), to subsequent experimental challenge with the infectious hematopoietic necrosis virus (IHNV). Immunological responses were examined at different organizational levels, from individuals to gene expression. No negative effects of PD were noted on the Fulton index nor on the liver or spleen somatic indices (LSI; SSI) before viral infection, but the infectious stress seems to generate a weak but significant decrease in Fulton and LSI values, which could be associated with consumption of energy reserves. During the viral challenges, the distribution of cumulative mortality was slightly different between infected groups. The impact of the virus on fish previously contaminated by PD started earlier and lasted longer than controls. The proportion of seropositive fish was lower in the fish group exposed to PD than in the control group, with similar quantities of anti-IHNV antibodies secreted in positive fish, regardless of the treatment. While no significant differences in C3-1 expression levels were detected throughout the experiment, TNF1&2, TLR3, Il-1ß and IFN expression levels were increased in all infected fish, but the difference was more significant in fish groups previously exposed to herbicide. On the other hand, ß-def expression was decreased in the pendimethalin-IHNV group compared to that in fish only infected by the virus (control-IHNV group).


Assuntos
Herbicidas/toxicidade , Imunidade Celular/efeitos dos fármacos , Imunidade Humoral/efeitos dos fármacos , Vírus da Necrose Hematopoética Infecciosa/fisiologia , Oncorhynchus mykiss/genética , Oncorhynchus mykiss/imunologia , Infecções por Rhabdoviridae/imunologia , Infecções por Rhabdoviridae/veterinária , Compostos de Anilina/toxicidade , Animais , Doenças dos Peixes/genética , Doenças dos Peixes/imunologia , Doenças dos Peixes/virologia , Regulação da Expressão Gênica/efeitos dos fármacos , Oncorhynchus mykiss/virologia , Infecções por Rhabdoviridae/genética , Infecções por Rhabdoviridae/patologia , Poluentes Químicos da Água/toxicidade
7.
Aquat Toxicol ; 216: 105285, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31546070

RESUMO

2-bromo-4, 6-dinitroaniline (BDNA) is a mutagenic aromatic amine involved in the production and degradation of Disperse blue 79, one of the most extensively used brominated azo dyes. In our previous study, a multigenerational exposure of BDNA (0.5, 5, 50 and 500 µg/L) to zebrafish from F0 adult to F2 larvae including a recovery group in F2 larvae was conducted. The effects on apical points observed in individuals and the long-term effects predicted on population were all related to reproduction. In this study, we performed molecular analysis to elucidate the underlying mechanisms of the reproductive toxicity of BDNA. In F1 generation, measurement of vitellogenin and transcription levels of genes associated with hypothalamus-pituitary-gland (HPG) axis, estrogen receptor (ER) and androgen receptor (AR) were conducted. There was a decrease in VTG level in the blood of F1 female fish and transcription of genes related to ER was more affected than that of genes related to AR. These results were consistent with adverse effects that sexual differentiation was biased towards males and fecundity was impaired in a concentration-dependent manner in adults of F1 generation after 150 days exposure. In F2 generation, global gene transcriptions of F2 larvae were investigated. It was uncovered that processes related to apoptosis, development and DNA damage were strongly affected. Alterations to these biological pathways accounted for the irreversible parental influence on a significant decrease in hatchability and increase in abnormality of F2 larvae. All evidence suggested that the multigenerational exposure of BDNA posed lasting effects transmitted from parents to offspring that persisted after exposure ceased.


Assuntos
Compostos de Anilina/toxicidade , Exposição Ambiental , Reprodução/efeitos dos fármacos , Testes de Toxicidade , Peixe-Zebra/metabolismo , Animais , Dano ao DNA , Feminino , Larva/efeitos dos fármacos , Larva/metabolismo , Masculino , Análise de Componente Principal , Transcrição Genética/efeitos dos fármacos , Transcriptoma/genética , Vitelogeninas/metabolismo , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/genética
8.
Regul Toxicol Pharmacol ; 107: 104419, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31301330

RESUMO

In 2016, the United States Environmental Protection Agency's (EPA) Office of Pesticide Programs published guidelines for establishing candidate common mechanism groups (CMGs) for cumulative risk assessment (CRA) weight-of-evidence-based screenings. A candidate CMG is a group of chemicals that may share similar structure, apical endpoints, and/or mechanistic data that suggest the potential for a common mechanism of toxicity among them. Here, a weight-of-evidence approach is presented to establish candidacy of a CMG for a group of nine dinitroaniline pesticides. This approach involves review of available in vivo toxicity information and literature to determine mode of action, along with analyses of in vitro toxicity data and chemical structure. Despite structural similarity among some dinitroanilines and some shared target organs identified through toxicity observed in in vivo studies, there were no consistencies among groups, suggesting lack of a common mechanism when all analyses are considered together. For example, two structurally similar compounds with thyroid/liver in vivo effects were not found active in any Toxicity Forecaster (ToxCast) in vitro assays. The weight-of-evidence is insufficient to support the testable hypothesis that dinitroanilines could form a CMG, and highlights the importance of establishing a consensus among multiple lines of evidence prior to CRA.


Assuntos
Compostos de Anilina/toxicidade , Praguicidas/toxicidade , Medição de Risco/métodos , Compostos de Anilina/química , Animais , Bioensaio , Simulação por Computador , Humanos , Praguicidas/química , Relação Estrutura-Atividade , Testes de Toxicidade
9.
Chemosphere ; 233: 920-935, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31340420

RESUMO

The current study aimed to investigate the impacts of different concentrations of GO/PANI nanocomposites (25, 50 and 100 mg L-1), in comparison with GO and PANI, on seed germination behaviors, morpho-physiological and biochemical traits in intact (mucilaginous) and demucilaged seeds, and young seedlings of the medicinal plant Salvia mirzayanii. Upon exposure to GO, seed germination was delayed and reduced, and growth attributes (root and shoot length, shoot fresh weight, and total chlorophyll content) declined, all of which could be attributed to the reductions in water uptake and oxidative stress particularly in demucilaged seeds. A hormetic dose-dependent response was observed for the growth traits in both intact and demucilaged seedlings upon exposure to GO/PANI concentrations, i.e. low-concentration stimulation and high-concentration repression. Elevated levels of H2O2 in shoot tissue of the seedlings exposed to GO and high concentration of GO/PANI, in comparison with those exposed to low levels of GO/PANI and control, were linked with the activities of the antioxidant enzymes SOD, CAT, POD, and total phenolics. Overall, the results showed high toxicity of GO on germination and early growth of S. mirzayani that was more evident in demucilaged seedlings, whereas GO/PANI stimulated germination, and the effects on seedling growth were stimulatory or inhibitory depending on the application dose and presence of mucilage. Furthermore, the capacity of GO/PANI nanocomposites to improve germination and cause a regular porosity pattern in roots accompanied by improved water uptake and early establishment of S. mirzayanii propose potential implications of GO/PANI nanocomposites for seeds/plants in drought-prone ecosystems.


Assuntos
Compostos de Anilina/toxicidade , Antioxidantes/farmacologia , Germinação/efeitos dos fármacos , Grafite/toxicidade , Salvia/metabolismo , Plântula/crescimento & desenvolvimento , Sementes/efeitos dos fármacos , Catalase/metabolismo , Clorofila , Peróxido de Hidrogênio/farmacologia , Nanocompostos , Estresse Oxidativo/efeitos dos fármacos , Mucilagem Vegetal/metabolismo , Superóxido Dismutase/metabolismo , Água
10.
Eur J Med Chem ; 178: 214-231, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31185412

RESUMO

Discovery of antimicrobial agents with a novel model of action is in urgent need for the clinical management of multidrug-resistant bacterial infections. Recently, we reported the identification of a first-in-class bacterial ribosomal RNA synthesis inhibitor, which interrupted the interaction between the bacterial transcription factor NusB and NusE. In this study, a series of diaryl derivatives were rationally designed and synthesized based on the previously established pharmacophore model. Inhibitory activity against the NusB-NusE binding, circular dichroism of compound treated NusB, antimicrobial activity, cytotoxicity, hemolytic property and cell permeability using Caco-2 cells were measured. Structure-activity relationship and quantitative structure-activity relationship were also concluded and discussed. Some of the derivatives demonstrated improved antimicrobial activity than the hit compound against a panel of clinically important pathogens, lowering the minimum inhibition concentration to 1-2 µg/mL against Staphylococcus aureus, including clinical strains of methicillin-resistant Staphylococcus aureus at a level comparable to some of the marketed antibiotics. Given the improved antimicrobial activity, specific inhibition of target protein-protein interaction and promising pharmacokinetic properties without significant cytotoxicity, this series of diaryl compounds have high potentials and deserve for further studies towards a new class of antimicrobial agents in the future.


Assuntos
Compostos de Anilina/farmacologia , Antibacterianos/farmacologia , Benzilaminas/farmacologia , Ligação Proteica/efeitos dos fármacos , Bases de Schiff/farmacologia , Compostos de Anilina/síntese química , Compostos de Anilina/química , Compostos de Anilina/toxicidade , Antibacterianos/síntese química , Antibacterianos/química , Antibacterianos/toxicidade , Proteínas de Bactérias/metabolismo , Benzilaminas/síntese química , Benzilaminas/química , Benzilaminas/toxicidade , Células CACO-2 , Desenho de Fármacos , Eritrócitos/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Células HeLa , Hemólise/efeitos dos fármacos , Humanos , Queratinócitos/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Bases de Schiff/síntese química , Bases de Schiff/química , Bases de Schiff/toxicidade , Relação Estrutura-Atividade , Fatores de Transcrição/metabolismo
11.
Ecotoxicol Environ Saf ; 180: 326-332, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31100596

RESUMO

Aniline and aniline derivatives have been widely used in the production of pesticides, pharmaceuticals, cosmetic, dyes, rubber, and adhesives products. These chemicals can easily be released into the environment through industrial and municipal discharges or as degradation byproducts. Several studies have suggested that aniline and some of its derivatives could cause reproductive toxicity in aquatic organisms. However, knowledge on the endocrine disruption potentials of these chemicals is limited only to aniline and associated mechanisms are rarely investigated. The objective of this study was to investigate the potential of major aniline derivatives, i.e., 3,4-dichloroaniline (3,4-DCA), 1-naphthylamine (1-NPA), and 4,4'-methylenedianiline (4,4'-MDA), to disrupt sex steroid production and other biological processes. For this purpose, the human adrenal H295R cell line and adult male zebrafish (Danio rerio) were used. In the H295R cell line, all tested aniline derivatives decreased testosterone (T) levels. Regulatory changes of several steroidogenic genes, i.e., down-regulation of StAR or CYP17 genes, and up-regulation of CYP19A, observed in the H295R cells could explain the sex hormone disruption. In male zebrafish, generally similar directions of changes, i.e., decreases in T levels and increased E2/T ratios, were observed. Again, down-regulation of key steroidogenic genes such as cyp17 or 3ß-hsd, but slight up-regulation of cyp19a gene observed in the fish could explain the sex hormone changes. The results of our study demonstrate that all tested aniline derivatives could influence steroidogenesis and disrupt sex hormone balance toward reduced androgenicity. Consequences of anti-androgenicity following long-term exposure warrant further investigation.


Assuntos
Glândulas Suprarrenais/efeitos dos fármacos , Compostos de Anilina/toxicidade , Disruptores Endócrinos/toxicidade , Testosterona/metabolismo , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/metabolismo , Glândulas Suprarrenais/metabolismo , Animais , Aromatase/genética , Linhagem Celular , Família 17 do Citocromo P450/genética , Relação Dose-Resposta a Droga , Humanos , Masculino , Fosfoproteínas/genética
12.
Nat Chem ; 11(6): 578-586, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30988414

RESUMO

Polymerization reactions conducted inside cells must be compatible with the complex intracellular environment, which contains numerous molecules and functional groups that could potentially prevent or quench polymerization reactions. Here we report a strategy for directly synthesizing unnatural polymers in cells through free radical photopolymerization using a number of biocompatible acrylic and methacrylic monomers. This offers a platform to manipulate, track and control cellular behaviour by the in cellulo generation of macromolecules that have the ability to alter cellular motility, label cells by the generation of fluorescent polymers for long-term tracking studies, as well as generate a variety of nanostructures within cells. It is remarkable that free radical polymerization chemistry can take place within such complex cellular environments. This demonstration opens up a multitude of new possibilities for how chemists can modulate cellular function and behaviour and for understanding cellular behaviour in response to the generation of free radicals.


Assuntos
Radicais Livres/química , Polimerização/efeitos da radiação , Ácidos Polimetacrílicos/síntese química , Poliestirenos/síntese química , Acrilatos/química , Acrilatos/efeitos da radiação , Acrilatos/toxicidade , Citoesqueleto de Actina/efeitos dos fármacos , Compostos de Anilina/química , Compostos de Anilina/efeitos da radiação , Compostos de Anilina/toxicidade , Movimento Celular/efeitos dos fármacos , Fluorescência , Células HeLa , Humanos , Metacrilatos/química , Metacrilatos/efeitos da radiação , Metacrilatos/toxicidade , Propano/análogos & derivados , Propano/química , Propano/efeitos da radiação , Fase S/efeitos dos fármacos , Estirenos/química , Estirenos/efeitos da radiação , Estirenos/toxicidade , Raios Ultravioleta , Compostos de Vinila/química , Compostos de Vinila/efeitos da radiação , Compostos de Vinila/toxicidade
13.
J Am Anim Hosp Assoc ; 55(3): e55302, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30870606

RESUMO

Two cats were presented with multifocal neurological signs. One cat's signs progressed over 2 wk; the other cat progressed over 5 days. Examinations were consistent with a process involving the prosencephalon, vestibular system, and general proprioceptive/upper motor neuron systems. MRI of the brain and cervical spinal cord reveal widespread T2 hyperintensity of the white matter. Affected areas included the cerebrum, cerebral peduncles, corticospinal tracts of the pons and medulla, and the cerebellum. T2 hyperintensity was present in all funiculi of the spinal cord. Diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) maps were consistent with cytotoxic or intramyelinic edema. Differential diagnosis included toxic or metabolic/degenerative leukoencephalopathies. Necropsies revealed widespread spongy degeneration of the central nervous system white matter. Toxicologic assays of liver specimens revealed desmethylbromethalin, a metabolite of bromethalin. Bromethalin is a rodenticide that causes uncoupling of oxidative phosphorylation. Antemortem diagnosis is challenging. DWI and ADC maps were instrumental in narrowing the differential diagnosis and raised the index of suspicion for bromethalin. Bromethalin intoxication should be considered in all animals with a progressive course of multifocal neurologic deficits. MRI, specifically, DWI and ADC maps, may serve as a biomarker of cytotoxic or intramyelinic edema associated with spongiform leukoencephalomyelopathy.


Assuntos
Compostos de Anilina/toxicidade , Doenças do Gato/induzido quimicamente , Imagem por Ressonância Magnética/veterinária , Rodenticidas/toxicidade , Animais , Doenças do Gato/diagnóstico por imagem , Doenças do Gato/patologia , Gatos , Feminino , Masculino
14.
Sci Total Environ ; 663: 560-567, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30726764

RESUMO

Quantitative structure-toxicity relationship (QSTR) models with the same mathematical structure were proposed for predicting the multiple toxicity endpoints of substituted phenols and anilines towards Chlorella vulgaris (C. vulgaris) based on the norm indexes. Four aquatic toxicity endpoints including growth inhibition concentrations of IC50, IC20, LOEC and NOEC towards C. vulgaris were involved in the modeling work. The results indicated that the developed models could produce satisfactory predictive results for the four different toxicity endpoints with high squared correlation coefficients (R2). Leave-one-out cross validation, Y-randomized validation and application domain analysis demonstrated the accuracy, robustness and reliability of these models. Accordingly, the results obtained in this work suggested that it might be possible to develop QSTR models with the same mathematical structure for predicting multiple toxicity endpoints successfully via norm index descriptors.


Assuntos
Compostos de Anilina/toxicidade , Chlorella vulgaris/efeitos dos fármacos , Fenóis/toxicidade , Relação Quantitativa Estrutura-Atividade , Poluentes Químicos da Água/toxicidade , Modelos Biológicos , Modelos Químicos
15.
Curr Neuropharmacol ; 17(3): 201-213, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30081786

RESUMO

Aniline exposure leads to neuron and spleen toxicity specifically and makes diverse neurological effects and sarcoma that is defined by splenomegaly, hyperplasia, and fibrosis and tumors formation at the end. However, the molecular mechanism(s) of aniline-induced spleen toxicity is not understood well, previous studies have represented that aniline exposure results in iron overload and initiation of oxidative/nitrosative disorder stress and oxidative damage to proteins, lipids and DNA subsequently, in the spleen. Elevated expression of cyclins, cyclin-dependent kinases (CDKs) and phosphorylation of pRB protein along with increases in A, B and CDK1 as a cell cycle regulatory proteins cyclins, and reduce in CDK inhibitors (p21 and p27) could be critical in cell cycle regulation, which contributes to tumorigenic response after aniline exposure. Aniline-induced splenic toxicity is correlated to oxidative DNA damage and initiation of DNA glycosylases expression (OGG1, NEIL1/2, NTH1, APE1 and PNK) for removal of oxidative DNA lesions in rat. Oxidative stress causes transcriptional up-regulation of fibrogenic/inflammatory factors (cytokines, IL- 1, IL-6 and TNF-α) via induction of nuclear factor-kappa B, AP-1 and redox-sensitive transcription factors, in aniline treated-rats. The upstream signalling events as phosphorylation of IκB kinases (IKKα and IKKß) and mitogen-activated protein kinases (MAPKs) could potentially be the causes of activation of NF-κB and AP-1. All of these events could initiate a fibrogenic and/or tumorigenic response in the spleen. The spleen toxicity of aniline is studied more and the different mechanisms are suggested. This review summarizes those events following aniline exposure that induce spleen toxicity and neurotoxicity.


Assuntos
Compostos de Anilina/toxicidade , Carcinógenos/toxicidade , Regulação da Expressão Gênica/efeitos dos fármacos , Síndromes Neurotóxicas/etiologia , Esplenopatias/induzido quimicamente , Animais , Modelos Animais de Doenças , Síndromes Neurotóxicas/metabolismo , Ratos , Esplenopatias/metabolismo
16.
Ecotoxicol Environ Saf ; 169: 654-661, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30496998

RESUMO

The environmental risk issues of p-choroaniline have been concerned by the widespread application and transportation of this important chemical intermediate. The information about the toxicity of p-chloroaniline was mainly concentrated on freshwater organisms while the current knowledge on marine organisms was scarce yet. In this study, acute toxicity and toxic physiology characteristic of p-chloroaniline to Phaeodactylum tricornutum (P. tricornutum) were first determined. In the acute experiments, the effect of the p-choroaniline to P. tricornutum showed time- and dose-dependent response, which the half maximum effective concentration (EC50) at 24 h, 48 h and 96 h was 35.35, 20.10 and 10.00 mgL-1, respectively. Toxic physiology assays in P. tricornutum indicated that the p-choroaniline induced significant changes of photosynthetic pigments (Chl-a, Chl-b, Caro, Chl-a/b and Chl-(a+b)/Caro), Chlorophyll fluorescence parameters (Fv/Fm, ETR, qP and NPQ), rates of photosynthetic O2 release and respiration O2 consumption, and antioxidant enzyme activities (SOD, CAT). The obvious decrease of Fv/Fm, ETR and chl-a in low p-choroaniline treatments (≤ 5.00 mgL-1) compared with the control could be observed, which implied that these parameters could be taken as sensitive indicators for the environmental assessment. Meanwhile, the activities of SOD and CAT significant increase in p-choroaniline stress after 24 h and the extent of the increase has fallen after 96 h. These toxicity data obtained here might provide available basic data for the ecological risk assessment of p-choroaniline pollution.


Assuntos
Compostos de Anilina/toxicidade , Antioxidantes/metabolismo , Diatomáceas , Consumo de Oxigênio/efeitos dos fármacos , Fotossíntese/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Clorofila/metabolismo , Diatomáceas/efeitos dos fármacos , Diatomáceas/enzimologia , Diatomáceas/crescimento & desenvolvimento , Testes de Toxicidade Aguda , Testes de Toxicidade Subcrônica
17.
Fish Physiol Biochem ; 45(1): 71-82, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29982916

RESUMO

To assess the ameliorative effects of Moringa oleifera (MO) leaf extract on haematological and biochemical changes, liver DNA damage and oxidative stress biomarkers in Nile tilapia (Oreochromis niloticus) exposed to a sublethal concentration (0.52 mg/l) of pendimethalin (PM). Tilapia fish were allocated into four equal groups in tri-replicates as follows: first group was the control group, second group was treated with MO (20 ml/30 l water), third group was exposed to 0.52 mg PM/l and fourth group was exposed to 0.52 mg PM/l and treated with MO leaf extract (20 ml/30 l water) for 28 days. At the end of this period, blood and liver tissue samples were collected and haematological and biochemical changes, hepatic DNA fragmentation and oxidative stress biomarkers were analysed. Pendimethalin caused significant reduction in haematological profile [White blood cells (WBCs) and red blood cells (RBCs) counts, haemoglobin (Hb) concentration and haematocrit (Ht) level]; meanwhile, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), creatinine, uric acid, glucose, cortisol, cholesterol and lactate dehydrogenase (LDH) were significantly increased. On the other hand, serum total protein, albumin, globulin and acetylcholinesterase (AChE) were decreased. Significant reduction in hepatic superoxide dismutase (SOD), catalase (CAT), total antioxidant capacity (TAC) and glutathione peroxidase (GSH-Px) levels and marked increments of hepatic malondialdehyde (MDA) and DNA fragmentation were observed in PM-exposed fish compared to the control group. The addition of Moringa oleifera leaf extract into the water could overcome the negative impacts of pendimethalin and normalise the examined parameters nearly to the control values. Moringa oleifera was used for the first time to protect tilapia fish against PM-induced toxicity. The present study revealed that Moringa oleifera has potent antioxidant and antigenotoxic actions against pendimethalin toxicity.


Assuntos
Compostos de Anilina/toxicidade , Ciclídeos/metabolismo , Herbicidas/toxicidade , Moringa oleifera/química , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Ciclídeos/sangue , Ciclídeos/genética , Dano ao DNA/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Testes de Mutagenicidade/veterinária , Extratos Vegetais/química , Folhas de Planta/química
18.
Sci Rep ; 8(1): 17139, 2018 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-30459330

RESUMO

Male Wistar rats were exposed to herbicide, pendimethalin (PND) at varying oral doses of 62.5, 125 and 250 mg/kg b.w. for 14 days. Toxiological effects were assessed in terms of oxidative stress, DNA damage, histopathological alterations and induction of anti-inflammatory and apoptotic responses linked Bax, Bcl-2, IFN-γ, TNF-α and caspase-3 gene expression. In comparison with respective untreated controls, all exposure groups of PND exhibited significant changes in the oxidative stress markers (protein carbonylation and lipid peroxidation) and antioxidant defenses (GSH, SOD, CAT and GST) in liver and kidney tissues. The histopathological changes including leucocyte infiltration, pyknotic nuclei, necrosis, large bowman's space, shrinked renal cortex, were observed in the liver and kidney tissues of PND exposed rats. Significant DNA damage was recorded through comet assay in liver and kidney cells of treated animals as compared to control. Alteration in anti-inflammatory and apoptotic genes expression determined by RT-PCR, revealed the activation of intrinsic apoptotic pathway(s) under the PND induced cellular stress. A pronounced increase in Bax expression, caspase-3 activities and decreased Bcl-2 expressions were also associated with PND-induced apoptosis. Data from this study suggests that PND induces cellular toxicity and genetic perturbations which can alter the normal cellular and physiological functioning in rats.


Assuntos
Compostos de Anilina/toxicidade , Apoptose/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Animais , Apoptose/genética , Biomarcadores/metabolismo , Caspase 3/genética , Ensaio Cometa , Dano ao DNA/fisiologia , Regulação da Expressão Gênica/efeitos dos fármacos , Herbicidas/toxicidade , Inflamação/genética , Rim/efeitos dos fármacos , Rim/patologia , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Estresse Oxidativo/fisiologia , Ratos Wistar , Proteína X Associada a bcl-2/genética
19.
J Am Chem Soc ; 140(47): 16340-16352, 2018 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-30384600

RESUMO

Electrochromic materials (EMs) are widely used color-switchable materials, but their applications as stimuli-responsive biomaterials to monitor and control biological processes remain unexplored. This study reports the engineering of an organic π-electron structure-based EM (dicationic 1,1,4,4-tetraarylbutadiene, 12+) as a unique hydrogen sulfide (H2S)-responsive chromophore amenable to build H2S-activatable fluorescent probes (12+-semiconducting polymer nanoparticles, 12+-SNPs) for in vivo H2S detection. We demonstrate that EM 12+, with a strong absorption (500-850 nm), efficiently quenches the fluorescence (580, 700, or 830 nm) of different fluorophores within 12+-SNPs, while the selective conversion into colorless diene 2 via H2S-mediated two-electron reduction significantly recovers fluorescence, allowing for non-invasive imaging of hepatic and tumor H2S in mice in real time. Strikingly, EM 12+ is further applied to design a near-infrared photosensitizer with tumor-targeting and H2S-activatable ability for effective photodynamic therapy (PDT) of H2S-related tumors in mice. This study demonstrates promise for applying EMs to build activatable probes for molecular imaging of H2S and selective PDT of tumors, which may lead to the development of new EMs capable of detecting and regulating essential biological processes in vivo.


Assuntos
Compostos de Anilina/uso terapêutico , Corantes Fluorescentes/uso terapêutico , Sulfeto de Hidrogênio/análise , Fármacos Fotossensibilizantes/uso terapêutico , Estilbenos/uso terapêutico , Compostos de Anilina/síntese química , Compostos de Anilina/farmacologia , Compostos de Anilina/toxicidade , Animais , Linhagem Celular Tumoral , Desenho de Fármacos , Feminino , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/farmacologia , Corantes Fluorescentes/toxicidade , Células HEK293 , Humanos , Sulfeto de Hidrogênio/química , Sulfeto de Hidrogênio/metabolismo , Raios Infravermelhos , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Imagem Molecular/métodos , Nanopartículas/química , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/efeitos da radiação , Fármacos Fotossensibilizantes/toxicidade , Polímeros/química , Células RAW 264.7 , Oxigênio Singlete/metabolismo , Estilbenos/síntese química , Estilbenos/farmacologia , Estilbenos/toxicidade , Tiadiazóis/química , Compostos de Vinila/química , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Environ Int ; 121(Pt 1): 861-870, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30343185

RESUMO

Exposure to sunlight and certain pesticides can induce phototoxic responses. Long- and short-term exposure to the photoactivated pesticides can cause a variety of skin diseases. However, assessment of pesticide phototoxicity on human skin is difficult. In the present study, human skin keratinocytes were cultured in several forms: monolayer cell sheet, three-dimensional culture, and keratinocyte-fibroblast co-culture. A common fungicide, dicloran (DC, 2,6­dichloro­4­nitroaniline), was irradiated with simulated sunlight for 2 (DC-PD-2h) and 4 (DC-PD-4h) hours. Dicloran, and two purified intermediate photodegradation products, 2­chloro­1,4­benzoquinone (CBQ) and 1,4­benzoquinone (BQ), were applied in toxicity tests independently with the keratinocyte culture models. The cell migration, cell differentiation, pro-inflammatory molecule production, and dermal fibroblast cell activation were all measured in the keratinocytes treated with the chemicals described above. These parameters were used as references for dicloran phototoxicity assessment. Among all tested chemicals, the DC-PD-4h and BQ demonstrated elevated toxicities to the keratinocytes compared to dicloran based on our results. The application of DC-PD-4h or BQ significantly delayed the migration of keratinocytes in monolayer cell sheets, inhibited the keratinocyte differentiation, increased the production of pro-inflammatory molecules by 3D keratinocyte culture, and enhanced the ability of 3D cultured keratinocytes in the activation of co-cultured dermal fibroblast cells. In contrast, dicloran, DC-PD-2h, and CBQ showed minimal effects on the keratinocytes in all assays. The results suggested that the four-hour photodegraded dicloran was likely to induce inflammatory skin diseases in the natural human skin. The 1,4­benzoquinone, which is the predominant degradation product detected following 4 h of irradiation, was the main factor for this response. Photoactivation increased the risk of skin exposed to dicloran in nature. Our models provided an efficient tool in the assessment of toxicity changes in pesticide following normal use practices under typical environmental conditions.


Assuntos
Compostos de Anilina/toxicidade , Fungicidas Industriais/toxicidade , Queratinócitos/efeitos dos fármacos , Fotólise , Pele/efeitos dos fármacos , Células Cultivadas , Humanos , Pele/metabolismo , Águas Residuárias/análise
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