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1.
Medicine (Baltimore) ; 100(1): e24101, 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33429775

RESUMO

BACKGROUND: To evaluate dapagliflozin, canagliflozin, empagliflozin, ertugliflozin, and sotagliflozin according to their effect on the glycated hemoglobin A1c (HbA1c) level in patients with type 2 diabetes mellitus. METHODS: The Web of Science, PubMed, Cochrane Library, EMBASE, and Clinical Trials databases were electronically searched to collect randomized controlled trials of patients with type 2 diabetes mellitus through June 2020. Two researchers independently screened and evaluated the obtained studies and extracted the outcome indexes. RevMan 5.3 software was used to perform the meta-analysis and to create plots. RESULTS: Finally, 27 studies were selected and included in this study. The meta-analysis results showed that sodium-dependent glucose transporter (SGLT) inhibitors significantly reduced the HbA1c level in patients with type 2 diabetes mellitus. However, these results were highly heterogeneous, so we conducted a subgroup analysis. The results of the subgroup analysis suggested that by dividing populations into different subgroups, the heterogeneity of each group could be reduced. CONCLUSIONS: SGLT inhibitors had a good effect on the HbA1c level in patients with type 2 diabetes mellitus, but there might be differences in the efficacy of SGLT inhibitors in different populations. It is hoped that more studies will be conducted to evaluate the efficacy and safety of SGLT inhibitors in different populations. REGISTRATION NUMBER: CRD42020185025.


Assuntos
Hemoglobina A Glicada/análise , Inibidores do Transportador 2 de Sódio-Glicose/normas , Compostos Benzidrílicos/farmacologia , Compostos Benzidrílicos/normas , Compostos Benzidrílicos/uso terapêutico , Glicemia/análise , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Compostos Bicíclicos Heterocíclicos com Pontes/normas , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Canagliflozina/farmacologia , Canagliflozina/normas , Canagliflozina/uso terapêutico , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucosídeos/farmacologia , Glucosídeos/normas , Glucosídeos/uso terapêutico , Glicosídeos/farmacologia , Glicosídeos/normas , Glicosídeos/uso terapêutico , Humanos , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Fatores de Tempo
2.
Ecotoxicol Environ Saf ; 208: 111746, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33396072

RESUMO

Plasticizers are widespread environmental contaminants that have been described as obesogens in terrestrial vertebrates. However, its effects on fish lipids homeostasis are almost unknown. This work explores the use of PLHC-1 cells as an alternative model to assess the disruption of hepatic lipids by plastic additives and to gather information on the mode of action of these chemicals in fish. PLHC-1 lipid extracts were analyzed by flow injection coupled to high resolution mass spectrometry (FIA-ESI(+/-)-Orbitrap-Exactive) after 24 h exposure of the cells to the selected plasticizers: dibutyl phthalate (DBP), di-(2-ethylhexyl) phthalate (DEHP), bisphenol A (BPA), bisphenol F (BPF), and chlorinated bisphenol A diglycidyl ether (BADGE·2HCl). The analysis of the culture medium and the intracellular concentration of the chemicals revealed the highest bioconcentration of BADGE·2HCl, DBP and DEHP, which was in agreement with the strongest alteration of the cells lipidome. BADGE·2HCl induced a significant depletion of triacylglycerides (TGs), while DEHP and DBP stimulated the accumulation of TGs. Exposure to BPF induced the generation of reactive oxygen species in PLHC-1 cells and a significant depletion of phosphatidylcholine (PC)- and phosphatidylethanolamine (PE)-plasmalogens, and TGs (cell depots of polyunsaturated fatty acids). Overall, this study evidences different modes of action of plastic additives in topminnow liver cells, describes differential lipidomic signatures, and highlights the higher lipotoxicity of BADGE·2HCl and BPF compared to BPA.


Assuntos
Plásticos/toxicidade , Testes de Toxicidade/métodos , Poluentes Químicos da Água/toxicidade , Animais , Compostos Benzidrílicos , Dibutilftalato , Compostos de Epóxi , Fundulidae , Hepatócitos , Fígado/efeitos dos fármacos , Modelos Biológicos , Fenóis , Ácidos Ftálicos , Plastificantes/toxicidade
3.
Environ Pollut ; 269: 116223, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33316500

RESUMO

Five endocrine-disrupting compounds (EDCs) were determined in four urban wastewater treatment plants (WWTPs) of the Metropolitan Area of Monterrey (MAM) in two seasonal periods (winter and summer). The MAM, one of the most urbanized areas in Mexico, is characterized by high industrial activity and population density, leading to extensive use of several EDCs. In the MAM, ∼90% of urban and industrial wastewater is treated in WWTPs, where EDCs can be partially eliminated. In this work, dissolved levels of 17ß-estradiol (E2), 17α-ethinyl estradiol (EE2), bisphenol A (BPA), 4-nonylphenol (4NP), and 4-tert-octylphenol (4TOP) in wastewater were determined. The EDCs' determination was carried out through solid-phase extraction (SPE) and gas chromatography coupled to mass spectrometry (GC-MS). High EDCs levels (0.4-450 ng/L) were found in the influents of WWTPs, while concentrations in the effluents ranged from 0.2 to 26.8 ng/L, with E2, EE2, and 4TOP being the most persistent. The Spearman correlation analysis revealed the association between E2 and EE2 (r = 0.4835, p < 0.05), and between BPA and 4NP (r = 0.5180, p < 0.05), suggesting that these EDCs have similar sources. Also, E2, BPA, and 4TOP were positively correlated with the chemical oxygen demand (COD), biochemical oxygen demand (BOD), and total suspended solids (TSS) (r = 0.4080-0.5694, p < 0.05), indicating the association of the EDCs with the organic matter in the wastewater. The factor analysis confirmed the significant correlation of COD, BOD, TSS, temperature, and pH with the high occurrence of 4TOP during the summer. It was also confirmed that summer warmer temperatures favored the removal of BPA and 4NP in the studied WWTPs. Finally, the studied sites were classified by cluster analysis in three groups, revealing the impact that seasonality has on the behavior of the selected EDCs.


Assuntos
Disruptores Endócrinos , Poluentes Químicos da Água , Purificação da Água , Compostos Benzidrílicos , Disruptores Endócrinos/análise , Monitoramento Ambiental , México , Estações do Ano , Eliminação de Resíduos Líquidos , Poluentes Químicos da Água/análise , Qualidade da Água
4.
Ecotoxicol Environ Saf ; 207: 111521, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33254396

RESUMO

Phthalates (PAEs), bisphenol A (BPA), and oestrogenic compounds have become major concerns due to their endocrine-disrupting effect. However, few studies related to the occurrence of PAEs, BPA, and oestrogen in food and compost from different growth age livestock have been conducted. In this study, faeces, urine and food samples were collected from a typical livestock (cow) and a special livestock (pigeon) from concentrated animal feeding operations (CAFOs). The daily total oestrogen excretion of a single cow ranged from 192 µg/day to 671 µg/day, which was significantly higher than that of a single pigeon (0-0.01 µg/day). Conjugated oestrogens represented 22.0-46.0% of the total oestrogens excreted from cow faeces and 80.7-91.8% of those from cow urine, indicating that the form of the excreted oestrogens depends on the livestock species and type of excrement. BPA was all detected in all livestock manure and food, and the concentration in pigeon was 9.2-40.2 ng/g and 23.1 ng/g respectively, while that in cattle was 50.5-72.0 ng/g and 41.1 ng/g respectively. The results indicated that the food is significant sources of BPA entering the process of cow and pigeon breeding. Diethyl phthalate (DEP) was detected at high frequency in pigeon faeces samples, suggesting that pigeons were highly exposed to these plasticisers. The total oestradiol equivalent quantity (EEQt) of livestock origin in aquatic environments was estimated to be 2.99 ng/L, which was higher than the baseline hazard value (1 ng/L) (Xu et al., 2018). The study provides data on the emissions and sources of PAEs, BPA, and oestrogenic compounds from different livestock in CAFOs and demonstrates that food is a significant source of BPA entering livestock.


Assuntos
Ração Animal/análise , Compostos Benzidrílicos/análise , Poluentes Ambientais/análise , Estrogênios/análise , Contaminação de Alimentos/análise , Fenóis/análise , Ácidos Ftálicos/análise , Animais , Bovinos , China , Fezes/química , Feminino , Contaminação de Alimentos/estatística & dados numéricos , Humanos , Gado , Esterco/análise , Plastificantes
5.
Chemosphere ; 262: 128045, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33182117

RESUMO

The vulnerability to environmental insults is heightened at early stages of development. However, the neurotoxic potential of bisphenol A (BPA) and bisphenol S (BPS) at developmental windows remains unclear. To investigate the mechanisms mediating the developmental neurotoxicity, zebrafish embryos were treated with 0.01, 0.03, 0.01, 0.3, 1 µM BPA/BPS. Also, we used Tg(HuC:GFP) zebrafish to investigate whether BPA/BPS could induce neuron development. The reduction in body length, and increased heart rate were significant in 0.3 and 1 µM BPA/BPS groups. The green fluorescence protein (GFP) intensity increased at 72 hpf and 120 hpf in Tg(HuC:GFP) larvae which was consistent with the increased mRNA expression of elval3 following BPS treatments, an indication of the plausible effect of BPS on embryonic neuron development. Additionally, BPA/BPS treatments elicited hyperactivity and reduced static time in zebrafish larvae, suggesting behavioral alterations. Moreover, qRT-PCR results showed that BPA and BPS could interfere with the normal expression of development-related genes vegfa, wnt8a, and mstn1 at the developmental stages. The expression of neurodevelopment-related genes (ngn1, elavl3, gfap, α1-tubulin, mbp, and gap43) were significantly upregulated in BPA and BPS treatments, except for the remarkable downregulation of mbp and gfap elicited by BPA at 48 (0.03 µM) and 120 hpf (0.3 µM) respectively; ngn1 at 48 hpf for 0.1 µM BPS. Overall, our results highlighted that embryonic exposure to low concentrations of BPA/BPS could be deleterious to the central nervous system development and elicit behavioral abnormalities in zebrafish at developmental stages.


Assuntos
Compostos Benzidrílicos/toxicidade , Embrião não Mamífero/efeitos dos fármacos , Desenvolvimento Embrionário/efeitos dos fármacos , Neurogênese/efeitos dos fármacos , Fenóis/toxicidade , Sulfonas/toxicidade , Poluentes Químicos da Água/toxicidade , Peixe-Zebra , Animais , Embrião não Mamífero/metabolismo , Larva/efeitos dos fármacos , Larva/metabolismo , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/metabolismo
6.
Chemosphere ; 262: 128073, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33182155

RESUMO

Due to the multi-catalysis of the WO3 and excellent properties of the graphene (GO), a series of rGO-WO3 nanocomposites were prepared through the hydrothermal synthesis procedure by changing the material ratio, the reaction temperature and the reaction time in this paper, and then added it into a dielectric barrier discharge plasma (DBDP) system for investigating the bisphenol A (BPA)'s degradation and corresponding catalytic mechanism of the rGO-WO3 in the DBDP system. The obtained results show that there was an optimum dosage of the rGO-WO3 (40 mg/L) as well as the preparation conditions (5:1000 mass ratio of the GO and the WO3, 18 h reaction time and 120 °C reaction temperature) for achieving the highest catalytic effect, and the highest degradation rate constant of the BPA was 0.03129 min-1. The determined higher TOC removal, higher COD removal as well as UV-Vis analysis also demonstrated the catalysis of the rGO-WO3. The measurement of the change of the O3 and the H2O2 concentrations in the reaction system with or without the rGO-WO3 and with or without the BPA proved the catalysis of the rGO-WO3 on the ·OH formation, while the combination of the GO had the positive effect for enhancing the catalytic effect. A figure on the catalysis and degradation procedure of the BPA in the DBDP/rGO-WO3 system was provided in the paper.


Assuntos
Compostos Benzidrílicos/análise , Grafite/química , Nanocompostos/química , Óxidos/química , Fenóis/análise , Tungstênio/química , Poluentes Químicos da Água/análise , Purificação da Água/métodos , Catálise , Peróxido de Hidrogênio/química , Modelos Teóricos , Oxirredução , Ozônio/química
7.
Food Chem ; 338: 127656, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-32798821

RESUMO

Bisguaiacols are promising lignin-derivable alternatives to bisphenol A (BPA), but limited bioassay data are available on their estrogenic activity (EA). Herein, we investigated the estrogen receptor alpha (ERα)-mediated EA of six newly synthesized bisguaiacols, which differed in the number and location of methoxy substituents, through in vitro assays: MCF-7 cell proliferation and VM7Luc4E2 transactivation. The six bisguaiacols had undetectable EA at concentrations less than 10-7 M, most importantly, with significantly lower EA than BPA over an environmentally relevant range of 10-10-10-7 M. Adding a single methoxy group led to significant reduction in EA in all cases, relative to BPA and one petroleum-derived BPA analogue (bisphenol F, BPF), and the incorporation of more methoxy groups had subtler, but pronounced, impacts on either ERα binding or MCF-7 cell proliferation. In short, the six lignin-inspired bisguaiacols presented herein are viewed as promising sustainable alternatives to BPA and BPF.


Assuntos
Compostos Benzidrílicos/química , Estrogênios/química , Lignina/química , Fenóis/química , Compostos Benzidrílicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Estrogênios/metabolismo , Estrogênios/farmacologia , Humanos , Células MCF-7 , Oxirredução , Fenóis/farmacologia , Ligação Proteica , Relação Estrutura-Atividade , Ativação Transcricional/efeitos dos fármacos
8.
Ecotoxicol Environ Saf ; 207: 111299, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32927158

RESUMO

The analogues of biphenol A (BPA), including bisphenol S (BPS) and bisphenol B (BPB), are commonly used to replace the application of BPA in containers and wrappers of daily life. However, their safeties are questioned due to their similar chemical structure and possible physiological effects as BPA. To investigate the neurotoxic effects of BPA, BPS, and BPB as well as their underlying mechanism, IMR-32 cell line from male and SK-N-SH cell line from female were exposed respectively to BPA, BPS and BPB with concentrations of 1 nM, 10 nM, 100 nM, 1 µM, 10 µM, and 100 µM for 24 h. Additionally, 24 h exposure of BPA combining epigallocatechin gallate (EGCG) (4 µM and 8 µM for IMR-32 and SK-N-SH respectively) were conducted. Results demonstrated that BPs exposure could promote reactive oxygen species production and increase level of malondialdehyde (MDA) while decrease levels of superoxide dismutase (SOD). Intensive study revealed that after exposure to BPA mitochondrial membrane potential (MMP) dropped down and the protein expression levels of Bak-1, Bax, cytochrome c and Caspase-3 were up-regulated but Bcl-2 were down-regulated significantly. Moreover, apoptosis rate was raised and cell activity declined remarkably in the neuroblastoma cells. All the effects induced by BPA could be alleviated by the adding of EGCG, which similar alleviations could be inferred in IMR-32 and SK-N-SH cells induced by BPS and BPB. Furthermore, BPS showed lower neurotoxic effects compared to BPA and BPB. Interestingly, the neurotoxic effects of BPA on IMR-32 cells were significantly higher than those on SK-N-SH cells. In conclusion, the results suggested that BPA, BPS and BPB could induce oxidative stress and apoptosis via mitochondrial pathway in the neuroblastoma cells and male is more susceptible to BPs than female.


Assuntos
Apoptose/efeitos dos fármacos , Compostos Benzidrílicos/toxicidade , Disruptores Endócrinos/toxicidade , Mitocôndrias/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Fenóis/toxicidade , Sulfonas/toxicidade , Caspase 3/metabolismo , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Caracteres Sexuais
9.
Chemosphere ; 262: 127880, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32777607

RESUMO

BACKGROUND: Bisphenol A (BPA) is a well-known endocrine disruptor that affects male fertility. However, the main biological events through which BPA affects spermatogenesis remain to be identified. METHODS: Adult male mice were treated by feeding with drinking water containing BPA (0.2 µg/ml, 20 µg/ml, 200 µg/ml, respectively) for two months. Testes were collected for protein extraction or for immunohistochemical analysis. Epididymal spermatozoa were collected for sperm quality evaluation and male fertility assay by in vitro fertility (IVF). Serums were collected for detection of testosterone levels. Proteins associated with germ cell proliferation, meiosis, blood-testis barrier, and steroidogenesis production were examined in BPA-treated and control mice testes. CCK8 assay was used to detect the effect of BPA on the proliferation of GC-1 and GC-2 cells. RESULTS: The BPA-treated mice were characterized by decreased sperm quality, serum testosterone levels and, sub-fertile phenotype characterizing with low pregnancy rates and reduced fertilization efficiency. In lower BPA (0.2 µg/ml) treatment, PCNA and PLZF were down-expressed that indicated impaired germ cell proliferation. SYCP3 was down-expressed in BPA-treated mice, but expressions of other proteins associated with meiosis and blood-testis barrier were not significantly altered. CYP11A1 and HSD3B1 were down-expressed in BPA-treated mice that demonstrated reduced steroidogenesis activity. BPA has a concentration-dependent inhibition effect on the proliferation of GC-1 and GC-2 cells. Conclusively, low doses BPA exposure reduced mice sperm quality mainly by impairing germ cell proliferation, leading to reduced male fertility. The study would provide relevant information for investigation on molecular mechanisms and protective strategy on male production.


Assuntos
Compostos Benzidrílicos/toxicidade , Disruptores Endócrinos/toxicidade , Fenóis/toxicidade , Espermatozoides/fisiologia , Animais , Proliferação de Células/efeitos dos fármacos , Disruptores Endócrinos/metabolismo , Epididimo/efeitos dos fármacos , Feminino , Fertilidade/efeitos dos fármacos , Masculino , Camundongos , Gravidez , Espermatogênese/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Testículo/efeitos dos fármacos , Testes de Toxicidade Crônica
10.
Chemosphere ; 262: 127841, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32784060

RESUMO

Environmental pollutants suspected of disrupting the endocrine system are considered etiologic factors in the epidemic of metabolic disorders. As regulation of energy metabolism relies on the integrated action of a large number of hormones, we hypothesized that certain chemicals could trigger changes in glucocorticoid signaling. To this end, we exposed C57Bl6/J female and male mice between 5 and 20 weeks of age to a mixture of 2,3,7,8- tetrachlorodibenzo-p-dioxin (20 pg/kg body weight/day [bw/d]), polychlorobiphenyl 153 (200 ng/kg bw/d), di-[2-ethylhexyl]-phthalate (500 µg/kg bw/d) and bisphenol A (40 µg/kg bw/d). In female mice fed a standard diet (ST), we observed a decrease in plasma levels of leptin as well as a reduced expression of corticoid receptors Nr3c1 and Nr3c2, of leptin and of various canonical genes related to the circadian clock machinery in visceral (VAT) but not subcutaneous (SAT) adipose tissue. However, Nr3c1 and Nr3c2 mRNA levels did not change in high-fat-fed females exposed to pollutants. In ST-fed males, pollutants caused the same decrease of Nr3c1 mRNA levels in VAT observed in ST-fed females but levels of Nr3c2 and other clock-related genes found to be down-regulated in female VAT were enhanced in male SAT and not affected in male VAT. The expression of corticoid receptors was not affected in the livers of both sexes in response to pollutants. In summary, exposure to a mixture of pollutants at doses lower than the no-observed adverse effect levels (NoAELs) resulted in sex-dependent glucocorticoid signaling disturbances and clock-related gene expression modifications in the adipose tissue of ST-fed mice.


Assuntos
Poluentes Ambientais/toxicidade , Glucocorticoides/metabolismo , Tecido Adiposo/metabolismo , Animais , Compostos Benzidrílicos , Peso Corporal , Poluentes Ambientais/metabolismo , Feminino , Expressão Gênica , Leptina/sangue , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fenóis , Dibenzodioxinas Policloradas/metabolismo , RNA Mensageiro/metabolismo , Sensibilidade e Especificidade
11.
Sci Total Environ ; 751: 141801, 2021 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-32861950

RESUMO

Bisphenols are increasingly recognized as environmental pollutants with endocrine-disrupting potential. Nonetheless, the study of environmental occurrence and some endocrine-disrupting activities of some bisphenols came widely into focus of research only recently. The aims of the present study were to: 1) determine the predominant bisphenols in Norwegian sewage sludge and sediment and in Czech surface waters, and 2) characterize the binding of bisphenols to a transport protein transthyretin (TTR) and their (anti-)thyroid, (anti-)progestagenic, and (anti-)androgenic activities. High-performance liquid chromatography with atmospheric pressure chemical ionization or photoionization coupled with high resolution mass spectrometry (HPLC-APCI/APPI-HRMS) and Chemically Activated LUciferase gene eXpression (CALUX) in vitro reporter gene bioassays were used to detect the target compounds and to determine endocrine-disrupting activities, respectively. Bisphenol A (BPA), 4,4'-bisphenol F (BPF), bisphenol S (BPS), and bisphenol E (BPE) were the most frequently found compounds in municipal sewage sludge. Furthermore, bisphenol TMC (BPTMC) and bisphenol AF (BPAF) frequently occurred in sediment and surface waters, respectively. BPA was the major contributor to Ʃ of bisphenols in Norwegian sewage sludge with exception of one sample where BPF predominated. We also monitored a few bisphenols in sediment but only BPTMC was found. BPA, BPAF and BPF were the dominant bisphenols in Czech surface waters. Some bisphenols have shown TTR binding potency (BPAF = BPF > BPA = BPE) and some have displayed the following endocrine-disrupting activities: anti-thyroid (BPAF), anti-progestagenic (BPTMC > BPA = BPAF), and anti-androgenic (BPAF > BPE > BPA > BPTMC > BPF > BPS). It is noteworthy that BPAF exhibited stronger or similarly potent endocrine-disrupting activities compared to BPA. Our results provide new insights into these less-studied endocrine-disrupting activities of environmentally relevant bisphenols and may be useful in prioritizing those compounds that deserve further attention in environmental monitoring and eco-toxicological research.


Assuntos
Poluentes Ambientais , Pré-Albumina , Compostos Benzidrílicos/análise , República Tcheca , Noruega , Fenóis , Pré-Albumina/genética
12.
Sci Total Environ ; 750: 141685, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32862004

RESUMO

Human exposure to bisphenol A (BPA) is unavoidable in daily life. Recently, research has showen that BPA could induce oxidative imbalance, thereby causing reproductive toxicity and liver dysfunction. Accumulated evidence has demonstrated that metformin possesses strong anti-oxidative properties. This study aimed to study the mechanism underlying the hepatic-protective effect of metformin on liver injury induced by BPA in rats via the UPLC-MS/MS metabolomics approach. Forty-two male rats were randomly divided into six groups (n = 7), namely the saline group (control), the corn oil group (vehicle), the metformin group (Met), the bisphenol A group (BPA), the bisphenol A and metformin group (BPA + Met), and the bisphenol A and diammonium glycyrrhizinate (positive control) group (BPA + DG). Serum was collected for biochemical analysis and metabolomics, and liver tissue was collected for histopathology and metabolomics in each group. We found that metformin could significantly reduce the levels of liver function enzymes (ALT, AST and GGT) and ameliorate inflammatory cell infiltration and hepatocyte necrosis induced by BPA. On the other hand, metformin could significantly enhance the total antioxidant capacity in BPA rats. Notably, metabolomics data indicated that the principal altered metabolic pathways based on the 26 differential metabolites in liver tissue, and 21 in serum among vehicle, BPA and BPA + Met groups, respectively, including cysteine and methionine metabolism, glutathione metabolism, and arginine biosynthesis and purine metabolism. Additionally, metformin significantly increased cystathionine ß synthase (CBS) and cystathionine γ lyase (CSE), thus reducing serum levels of homocysteine and increasing hepatic levels of cysteine and glutathione in BPA-treated rats. Overall, this study's results provided new insights into the role and mechanism of metformin in BPA-induced liver injury in rats.


Assuntos
Cistationina gama-Liase , Metformina , Animais , Compostos Benzidrílicos/toxicidade , Cromatografia Líquida , Cistationina beta-Sintase/metabolismo , Cistationina gama-Liase/metabolismo , Humanos , Fígado/metabolismo , Masculino , Metformina/toxicidade , Fenóis , Ratos , Espectrometria de Massas em Tandem , Regulação para Cima
13.
Sci Total Environ ; 753: 141949, 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-32891999

RESUMO

Bisphenol S (BPS) is the major substitute for the production of bisphenol A (BPA)-free products and detected in both food and environment. Although the relationship between BPA exposure and increased risk of obesity and diabetes has been noted, the potential influence of BPS is not fully understood. Herein, a non-targeted lipidomic study was performed to explore BPA/BPS exposure actions using the 3T3-L1 preadipocyte differentiation model, and revealed the comprehensive lipidome disturbance induced by either BPA or BPS exposure at different doses of 0.01, 1 and 100 µM. BPA was more potent than BPS in disturbance of lipid metabolism. A considerable similarity of BPS exposure to BPA was discovered. The key lipid remodeling in response to exposure was found to involve the cardiolipins, phosphatidylglycerols and fatty acids metabolic pathways, providing novel clues of potential mechanism in which both BPA and BPS exposure could be associated with increased risk of insulin resistance. Our study supplies the perspective into the lipidome response to environmental stress induced by BPA/BPS, and shows that BPA-free products are not necessarily safer. Substitution of BPA by its structural analog BPS should be therefore performed with caution.


Assuntos
Compostos Benzidrílicos , Lipidômica , Animais , Compostos Benzidrílicos/toxicidade , Camundongos , Fenóis/toxicidade , Sulfonas
14.
Sci Total Environ ; 753: 141805, 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-32911163

RESUMO

Seahorses, with brood pouch in adult males, are a bioindicator species that exhibit specialized reproductive strategy of "male pregnancy". Bisphenol A (BPA), one of the most pervasive endocrine-disrupting chemicals (EDCs), is hazardous for reproductive, immune, and neurological systems. However, no evidence of BPA toxicity to the male-pregnant animals is available. Herein, the reproductive toxicity of BPA was evaluated in lined seahorses (Hippocampus erectus) following exposure to environmentally relevant concentrations (10, 100, and 1000 µg/L) through physiological, histological, and transcriptional analyses. Our results indicated BPA bioaccumulation to be positively correlated with exposure doses in both sexes. Ovarian failure was only observed in the high-dose BPA treatment group, accompanied by the apoptosis of follicular cells and up-regulation of pro-apoptotic genes. However, brood pouches maintenance were surprisingly inhibited at low concentration, and transcriptomic analysis revealed disturbed profiles of genes involved in the extracellular matrix and cell-cell adhesion pathways. Interestingly, seahorse testes were less sensitive to BPA exposure than that in other teleosts. Thus, our study suggests that BPA at environmentally relevant concentrations might cause reproductive dysfunction in seahorses, potentially exerting adverse effects on the seahorse population since most of them inhabit shallow coastal areas with prevalent estrogenic contaminants.


Assuntos
Disruptores Endócrinos , Smegmamorpha , Animais , Compostos Benzidrílicos/toxicidade , Bioacumulação , Disruptores Endócrinos/toxicidade , Feminino , Masculino , Fenóis/toxicidade
15.
Sci Total Environ ; 753: 142073, 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-32911175

RESUMO

The removal of bisphenol A (BPA) by waste zero-valent iron (ZVI) regulating microbial community in sequencing batch biofilm reactor (SBBR) was investigated. Compared with SBBR-BPA, the acclimation time of microorganisms in the presence of waste ZVI and BPA (SBBR-ZVI+BPA) decreased from 56 d to 49 d. During stable operation period, BPA was removed completely at 150th min and 100th min in the SBBR-BPA and SBBR-ZVI+BPA, respectively. The optimal initial pH and BPA concentration in the SBBRs were respectively 8.0 and 10 mg/L. The composition and content analysis of extracellular polymeric substances (EPS) using fluorescence spectrometer showed that the yield of EPS was enhanced by the addition of ZVI. The analysis of microbial community structure in the SBBRs using Illumina Miseq sequencing method indicated that the indexes of ACE, Chao1 and Shannon were higher and Simpson index was lower in the SBBR-ZVI+BPA. Moreover, the abundance of BPA biodegradation strains was increased in the presence of ZVI. This study provided a promising method with low cost of effectively removing BPA from wastewater.


Assuntos
Microbiota , Eliminação de Resíduos Líquidos , Compostos Benzidrílicos , Biofilmes , Reatores Biológicos , Ferro , Fenóis , Águas Residuárias
16.
Food Chem ; 338: 128031, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-32950007

RESUMO

A comprehensive study on packaging used in commercially available milk products from Spanish markets has been presented. Concentrations of four phthalates, seven parabens and BPA were determined in forty-two milk products. Eleven brands and five types of packaging (metallic aluminium bag, carton, high-density polyethylene, metal pail and polyethylene terephthalate) were included in the study. BPA showed the lowest concentrations (8.3 pg/g f.w.), far below those of phthalates (6431 pg/g f.w.) and parabens (6234 pg/g f.w.). Metallic aluminium bags were the least migrating packaging (considering plasticisers and monomers) followed by HDPE bottles, in the case of phthalates. Parabens showed their highest concentrations for fresh-milk samples. Levels found were far below the specific migration limits established by the EU and the cumulative hazard index was lower than 1, indicating that adverse health effects were not expected. In general, the results found in Spanish samples were lower than those reported in other countries.


Assuntos
Leite/química , Plastificantes/análise , Conservantes Farmacêuticos/análise , Animais , Compostos Benzidrílicos/análise , Humanos , Limite de Detecção , Parabenos/análise , Fenóis/análise , Ácidos Ftálicos/análise , Espanha
17.
Environ Pollut ; 270: 115721, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33321439

RESUMO

Increasing concerns over bisphenol A (BPA) as an endocrine disrupting chemical (EDC) and its adverse effects on both humans and animals have led to the substitution by structural analogs, such as bisphenol F (BPF), in many application areas. Information regarding to the carry-over of this emerging chemical in farm animals is essential for legislation and risk assessment purposes. In this study, a large-scale number of animal experiments were designed to investigate the transfer of BPF from feed to eggs. One control and three experimental groups of laying hens (72 hens per group) were fed with basal diets and BPF-contaminated feed at concentration levels of 0.1, 0.5 and 2.5 mg kg-1, respectively, for two weeks. The hens were then fed with BPF-free diets for a further four weeks. Eggs were collected daily, and separated into egg yolk and white for BPF analysis. The effects of different levels of BPF exposure on laying performance followed a non-monotonic dose-response curve, since low level BPF (0.1 mg kg-1) exposure did increase the laying rate, mean egg weight and daily feed intake, while high level BPF (2.5 mg kg-1) exposure showed a decreasing trend. BPF residues were detected in both egg yolks and whole eggs after two days of administration, and plateau phase was achieved within 9-18 days. There are clear linear dose-response relationships between the plateau BPF concentrations in feed and eggs. The residue of BPF was found mainly in egg yolks with conjugated form and depleted slowly (still detected 21 days after feeding the BPF-free diet of the high level group). Mean carry-over rate of 0.59% BPF from feed to eggs was obtained. Compared with the carry-over rates of PCBs and dioxins, BPF showed a relatively minor trend of bioaccumulation in eggs. To the best of our knowledge, this is the first report on the deposition, depletion, and bioaccumulation study of bisphenols in farm animals. The quantity of data can therefore be helpful in the frame of risk assessment, especially for a comprehensive estimation of consumer exposure to the residues of bisphenols.


Assuntos
Ração Animal , Galinhas , Ração Animal/análise , Animais , Compostos Benzidrílicos , Bioacumulação , Dieta , Ovos , Feminino , Humanos , Fenóis
18.
Environ Pollut ; 270: 116192, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33338957

RESUMO

Polyethylene terephthalate (PET) is a possible key component of nanoplastics in water environments, which can migrate pollutants through co-transport. In this regard, the co-transport of endocrine disruptors (such as bisphenol A, BPA) by nanoplastics is of emergent concern because of its cytotoxicity/bioaccumulation effects in aquatic organisms. In this work, a computational study is performed to reveal the BPA adsorption mechanism onto PET nanoplastics (nanoPET). It is found that the outer surface of nanoPET has a nucleophilic nature, allowing to increase the mass transfer and intraparticle diffusion into the nanoplastic to form stable complexes by inner and outer surface adsorption. The maximum adsorption energy is similar (even higher) in magnitude with respect to nanostructured adsorbents such as graphene, carbon nanotubes, activated carbon, and inorganic surfaces, indicating the worrying adsorption properties of nanoPET. The adsorption mechanism is driven by the interplay of dispersion (38-49%) and electrostatics effects (43-50%); specifically, dispersion effects dominate the inner surface adsorption, while electrostatics energies dominate the outer surface adsorption. It is also determined that π-π stacking is not a reliable interaction mechanism for aromatics on nanoPET. The formed complexes are also highly soluble, and water molecules behave as non-competitive factors, establishing the high risk of nanoPET to adsorb and migrate pollutants in water ecosystems. Furthermore, the adsorption performance is decreased (but not inhibited) at high ionic strength in salt-containing waters. Finally, these results give relevant information for environmental risk assessment, such as quantitative data and interaction mechanisms for non-biodegradable nanoplastics that establish strong interactions with pollutants in water.


Assuntos
Nanotubos de Carbono , Poluentes Químicos da Água , Adsorção , Compostos Benzidrílicos , Ecossistema , Microplásticos , Modelos Teóricos , Fenóis , Polietilenotereftalatos , Poluentes Químicos da Água/análise
19.
Chemosphere ; 267: 129296, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33348264

RESUMO

The aim of this study was to: (i) determine and compare the capacity of bis (2 -ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP), bisphenol A (BPA), and their mixture to produce testicular toxicity after the subacute exposure; (ii) explore the mechanisms behind the observed changes using in silico toxicogenomic approach. Male rats were randomly split into groups (n = 6): (1) Control (corn oil); (2) DEHP (50 mg/kg b.w./day); (3) DBP (50 mg/kg b.w./day); (4) BPA (25 mg/kg b.w./day); and (5) MIX (50 mg/kg b.w./day DEHP + 50 mg/kg b.w/day DBP + 25 mg/kg b.w./day BPA). Animals were sacrificed after 28 days of oral exposure, testes were extracted and prepared for histological assessments under the light microscope (haematoxylin and eosin staining) and redox status analysis. The Comparative Toxicogenomics Database (CTD; http://CTD.mdibl.org), Cytoscape software (https://cytoscape.org) and ToppGene Suite (https://toppgene.cchmc.org) were used for data-mining. Present pathohistological study has demonstrated more pronounced testicular toxicity of the MIX group (desquamated germinal epithelium cells, enlarged cells with hyperchromatic nuclei, multinucleated cell forms and intracytoplasmic vacuoles) in comparison with the single substances, while effects on redox status parameters were either more prominent, or present only in the MIX group. In silico investigation revealed 20 genes linked to male reproductive disorders, affected by all three investigated substances. Effects on metabolism, AhR pathway, apoptosis and oxidative stress could be singled out as the most probable mechanisms involved in the subacute DEHP, DBP and BPA mixture testicular toxicity, while the effect on oxidative stress parameters was confirmed by in vivo experiment.


Assuntos
Dietilexilftalato , Testículo , Animais , Compostos Benzidrílicos , Simulação por Computador , Dietilexilftalato/metabolismo , Dietilexilftalato/toxicidade , Masculino , Oxirredução , Fenóis , Ácidos Ftálicos , Ratos , Testículo/metabolismo , Toxicogenética
20.
Lancet Diabetes Endocrinol ; 9(1): 22-31, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33338413

RESUMO

BACKGROUND: Dapagliflozin reduces the risk of kidney failure and heart failure in patients with chronic kidney disease. We aimed to investigate the effects of dapagliflozin on kidney, cardiovascular, and mortality outcomes according to presence or absence of type 2 diabetes and according to underlying cause of chronic kidney disease, reported as diabetic nephropathy, chronic glomerulonephritides, ischaemic or hypertensive chronic kidney disease, or chronic kidney disease of other or unknown cause. METHODS: DAPA-CKD was a multicentre, double-blind, placebo-controlled, randomised trial done at 386 study sites in 21 countries, in which participants with a urinary albumin-to-creatinine ratio of 200-5000 mg/g and an estimated glomerular filtration rate (eGFR) of 25-75 mL/min per 1·73m2 were randomly assigned (1:1) to dapagliflozin 10 mg once daily or matching placebo, as an adjunct to standard care. The primary outcome was a composite of sustained decline in eGFR of at least 50%, end-stage kidney disease, or kidney-related or cardiovascular death. Secondary efficacy outcomes were a kidney-specific composite (the same as the primary outcome but excluding cardiovascular death), a composite of cardiovascular death or hospital admission for heart failure, and all-cause mortality. In this study, we conducted a prespecified subgroup analysis of the DAPA-CKD primary and secondary endpoints by presence or absence of type 2 diabetes and by aetiology of chronic kidney disease. DAPA-CKD is registered with ClinicalTrials.gov, NCT03036150. FINDINGS: The study took place between Feb 2, 2017, and June 12, 2020. 4304 participants were randomly assigned (2152 to dapagliflozin and 2152 to placebo) and were followed up for a median of 2·4 years (IQR 2·0-2·7). Overall, 2906 (68%) participants had a diagnosis of type 2 diabetes, of whom 396 (14%) had chronic kidney disease ascribed to causes other than diabetic nephropathy. The relative risk reduction for the primary composite outcome with dapagliflozin was consistent in participants with type 2 diabetes (hazard ratio [HR] 0·64, 95% CI 0·52-0·79) and those without diabetes (0·50, 0·35-0·72; pinteraction=0·24). Similar findings were seen for the secondary outcomes: kidney-specific composite outcome (0·57 [0·45-0·73] vs 0·51 [0·34-0·75]; Pinteraction=0·57), cardiovascular death or hospital admission for heart failure (0·70 [0·53-0·92] vs 0·79 [0·40-1·55]; Pinteraction=0·78), and all-cause mortality (0·74 [0·56-0·98] vs 0·52 [0·29-0·93]; Pinteraction=0·25). The effect of dapagliflozin on the primary outcome was also consistent among patients with diabetic nephropathy (n=2510; HR 0·63, 95% CI 0·51-0·78), glomerulonephritides (n=695; 0·43, 0·26-0·71), ischaemic or hypertensive chronic kidney disease (n=687; 0·75, 0·44-1·26), and chronic kidney disease of other or unknown cause (n=412; 0·58, 0·29-1·19; Pinteraction=0·53), with similar consistency seen across the secondary outcomes. The proportions of participants in the dapagliflozin and placebo groups who had serious adverse events or discontinued study drug due to adverse events did not vary between those with and those without type 2 diabetes. INTERPRETATION: Dapagliflozin reduces the risks of major adverse kidney and cardiovascular events and all-cause mortality in patients with diabetic and non-diabetic chronic kidney disease. FUNDING: AstraZeneca.


Assuntos
Compostos Benzidrílicos/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucosídeos/uso terapêutico , Insuficiência Cardíaca/induzido quimicamente , Falência Renal Crônica/induzido quimicamente , Adulto , Idoso , Compostos Benzidrílicos/efeitos adversos , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/epidemiologia , Método Duplo-Cego , Feminino , Glucosídeos/efeitos adversos , Insuficiência Cardíaca/epidemiologia , Humanos , Rim/efeitos dos fármacos , Rim/patologia , Rim/fisiopatologia , Falência Renal Crônica/epidemiologia , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/epidemiologia , Resultado do Tratamento
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