Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.272
Filtrar
1.
J Agric Food Chem ; 68(5): 1257-1265, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31927919

RESUMO

Bedaquiline (TMC-207) is a recently approved drug for the treatment of multidrug-resistant tuberculosis (MDR-TB). Moreover, there is a present and growing concern for natural-product-mediated drug interaction, as these are inadvertently taken by patients as a dietary supplement, food additive, and medicine. In the present study, we investigated the impact of 20 plant-based natural products, typically phenolics, on in vivo oral bedaquiline pharmacokinetics, as previous studies are lacking. Three natural phenolics were identified that can significantly enhance the oral exposure of bedaquiline upon coadministration. We further investigated the possible role of all of the phytochemicals on in vitro P-glycoprotein (P-gp) induction and inhibition and CYP3A4 inhibition in a single platform as bedaquiline is the substrate for both P-gp and CYP3A4. In conclusion, curcumin, CC-I (3',5-dihydroxyflavone-7-O-ß-d-galacturonide-4'-O-ß-d-glucopyranoside), and 6-gingerol should not be coadministered with bedaquiline to avoid untoward drug interactions and, subsequently, its dose-dependent adverse effects.


Assuntos
Antituberculosos/farmacocinética , Diarilquinolinas/farmacocinética , Suplementos Nutricionais/efeitos adversos , Interações Alimento-Droga , Fenóis/efeitos adversos , Extratos Vegetais/efeitos adversos , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Animais , Antituberculosos/administração & dosagem , Citocromo P-450 CYP3A/genética , Citocromo P-450 CYP3A/metabolismo , Diarilquinolinas/administração & dosagem , Suplementos Nutricionais/análise , Feminino , Humanos , Fenóis/administração & dosagem , Extratos Vegetais/administração & dosagem , Ratos , Ratos Wistar , Tuberculose Resistente a Múltiplos Medicamentos/genética , Tuberculose Resistente a Múltiplos Medicamentos/metabolismo
2.
Endocr Pract ; 26(4): 399-406, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31968191

RESUMO

Objective: To investigate whether serum bisphenol A (BPA) concentration is related to the occurrence of dyslipidemia. Methods: A total of 574 adults were enrolled at baseline and followed up for 5 years. Concentrations of serum BPA, triglycerides (TGs), low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol were measured. Dyslipidemia was defined as the existence of one or more of the following conditions: high-LDL-cholesterolemia (LDL ≥140 mg/dL), hypertriglyceridemia (TGs ≥150 mg/dL), or low-HDL-cholesterolemia (HDL <40 mg/dL). Participants were stratified into tertiles according to low, median, and high baseline serum BPA levels. Multivariable linear and logistic regression models were used. Data from baseline and follow-up were used for cross-sectional and longitudinal analyses, respectively. Results: In the cross-sectional analysis, compared to subjects in the low BPA tertile, those in the high BPA tertile showed a higher level of LDL cholesterol (108.1 ± 24.4 mg/dL versus 119.5 ± 26.9 mg/dL; P<.05) and a lower level of HDL cholesterol (46.2 ± 11.7 mg/dL versus 39.5 ± 7.5 mg/dL; P<.05). In multivariable linear regression models, Z-transformed BPA was positively associated with LDL cholesterol (ß= 0.13, P = .002) and negatively associated with HDL cholesterol (ß= -0.28; P<.001). After cross-sectionally adjusting for confounders, subjects in higher BPA exposure was associated with a higher prevalence of low-HDL-cholesterolemia. Longitudinally, in subjects without low-HDL-cholesterolemia at baseline, each SD increment in baseline BPA was associated with a higher incidence of low-HDL-cholesterolemia after adjustment for confounders (odds ratio [95% confidence interval; CI] 2.76, 95% CI 1.21, 6.29). Conclusion: Cross-sectionally, higher BPA exposure is associated with a higher prevalence of low-HDL-cholesterolemia. Longitudinally, baseline BPA is an independent predictor of the 5-year incidence of low-HDL-cholesterolemia. Abbreviations: BMI = body mass index; BPA = bisphenol A; CI = confidence interval; CVD = cardiovascular disease; EIMDS = environment, inflammation and metabolic diseases study; HDL = high density lipoprotein; LDL = low density lipoprotein; OR = odds ratio; PPAR = peroxisome proliferator-activated receptor; SBP = systolic blood pressure; TG = triglyceride; Z-BPA = Z-transformed bisphenol A.


Assuntos
Compostos Benzidrílicos/efeitos adversos , Dislipidemias , Fenóis/efeitos adversos , HDL-Colesterol , Estudos Transversais , Dislipidemias/induzido quimicamente , Disruptores Endócrinos , Humanos , Estudos Prospectivos , Fatores de Risco , Triglicerídeos
4.
Int J Mol Sci ; 20(24)2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31842455

RESUMO

Apolipoprotein A-I (apoA-I) is the major protein component of high-density lipoproteins (HDL), mediating many of its atheroprotective properties. Increasing data reveal the pro-atherogenic effects of bisphenol A (BPA), one of the most prevalent environmental chemicals. In this study, we investigated the mechanisms by which BPA exerts pro-atherogenic effects. For this, LDLR-/- mice were fed with a high-fat diet and treated with 50 µg BPA/kg body weight by gavage. After two months of treatment, the area of atherosclerotic lesions in the aorta, triglycerides and total cholesterol levels were significantly increased, while HDL-cholesterol was decreased in BPA-treated LDLR-/- mice as compared to control mice. Real-Time PCR data showed that BPA treatment decreased hepatic apoA-I expression. BPA downregulated the activity of the apoA-I promoter in a dose-dependent manner. This inhibitory effect was mediated by MEKK1/NF-κB signaling pathways. Transfection experiments using apoA-I promoter deletion mutants, chromatin immunoprecipitation, and protein-DNA interaction assays demonstrated that treatment of hepatocytes with BPA induced NF-κB signaling and thus the recruitment of p65/50 proteins to the multiple NF-κB binding sites located in the apoA-I promoter. In conclusion, BPA exerts pro-atherogenic effects downregulating apoA-I by MEKK1 signaling and NF-κB activation in hepatocytes.


Assuntos
Poluentes Ocupacionais do Ar/efeitos adversos , Apolipoproteína A-I/genética , Aterosclerose/etiologia , Aterosclerose/metabolismo , Compostos Benzidrílicos/efeitos adversos , Regulação da Expressão Gênica , NF-kappa B/metabolismo , Fenóis/efeitos adversos , Animais , Apolipoproteína A-I/metabolismo , Aterosclerose/sangue , Aterosclerose/patologia , Biomarcadores , Modelos Animais de Doenças , Feminino , Hepatócitos/metabolismo , Lipídeos/sangue , Masculino , Camundongos , Camundongos Knockout , Receptores de LDL/deficiência
5.
Int J Mol Sci ; 20(18)2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31489946

RESUMO

Maternal exposure to endocrine disrupting chemicals (EDCs) and a high-fat intake may induce the developmental programming of hypertension in adult offspring. Bisphenol A (BPA) is one of the most commonly environmental EDCs. As the nitric oxide (NO) and aryl hydrocarbon receptor (AHR) signaling pathways both contribute to the pathogenesis of hypertension, we evaluated whether resveratrol, an antioxidant and an AHR antagonist, can prevent hypertension programmed by a maternal BPA and HF diet. Sixteen-week-old male rat offspring were assigned to six groups (n = 8 per group): Control, HF (D12331, Research Diets), BPA (50 µg/kg/day), HF + BPA, BPA + R (resveratrol 50mg/L in drinking water throughout pregnancy and lactation), and HF + BPA + R. Maternal BPA exposure exacerbated hypertension programmed by HF consumption in adult male offspring, which was protected by maternal resveratrol therapy. The BPA and HF diet synergistically induced oxidative stress in offspring kidneys, which resveratrol treatment prevented. We observed that HF + BPA-induced programmed hypertension was associated with a decreased NO bioavailability, increased oxidative stress, and an activated AHR signaling pathway. The beneficial effects of resveratrol are relevant to restoring NO bioavailability, reducing oxidative stress, and antagonizing the AHR signaling pathway. Our results cast a new light on resveratrol as a reprogramming strategy to protect against hypertension programmed by combined BPA and HF exposure, but this strategy has yet to be translated into clinical applications.


Assuntos
Compostos Benzidrílicos/efeitos adversos , Dieta Hiperlipídica/efeitos adversos , Hipertensão/etiologia , Hipertensão/metabolismo , Exposição Materna , Fenóis/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal , Animais , Biomarcadores , Pressão Sanguínea/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Imuno-Histoquímica , Masculino , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Gravidez , Ratos , Resveratrol/farmacologia
6.
In Vivo ; 33(5): 1421-1423, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31471387

RESUMO

BACKGROUND/AIM: Bisphenol A (BPA) is a ubiquitous substance found in a wide array of consumer products and healthcare consumables, and at low doses in drinking water. Currently, in the UK, it is classed as a low-risk substance with little potential for harm. It has been known to have effects on oestrogen receptors. The implications of this for public safety is currently subject to debate. MATERIALS AND METHODS: In this study, we review recent literature regarding the effects and safety of BPA, and discuss the potential implications, in particular from the perspective of human breast oncogenesis. RESULTS AND CONCLUSION: Recent evidence suggests that low-doses of endocrine disruptors, such as BPA, could have profound effects in breast development and cancer risk. Recent studies in murine models suggest that BPA could contribute to breast oncogenesis via several pathways. The position of regulators should shift accordingly to safeguard the public interest.


Assuntos
Compostos Benzidrílicos/química , Compostos Benzidrílicos/farmacologia , Fenóis/química , Fenóis/farmacologia , Animais , Compostos Benzidrílicos/efeitos adversos , Disruptores Endócrinos/efeitos adversos , Disruptores Endócrinos/química , Disruptores Endócrinos/farmacologia , Exposição Ambiental/efeitos adversos , Humanos , Fenóis/efeitos adversos
7.
Nutrients ; 11(9)2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31500194

RESUMO

Bisphenol A (BPA) is the most well-known compound from the bisphenol family. As BPA has recently come under pressure, it is being replaced by compounds very similar in structure, but data on the occurrence of these BPA analogues in food and human matrices are limited. The main objective of this work was to investigate human exposure to BPA and analogues and the associated health effects. We performed a literature review of the available research made in humans, in in vivo and in vitro tests. The findings support the idea that exposure to BPA analogues may have an impact on human health, especially in terms of obesity and other adverse health effects in children.


Assuntos
Tecido Adiposo/efeitos dos fármacos , Adiposidade/efeitos dos fármacos , Compostos Benzidrílicos/efeitos adversos , Disruptores Endócrinos/efeitos adversos , Metabolismo Energético/efeitos dos fármacos , Contaminação de Alimentos , Obesidade/induzido quimicamente , Fenóis/efeitos adversos , Tecido Adiposo/metabolismo , Tecido Adiposo/fisiopatologia , Animais , Compostos Benzidrílicos/análise , Disruptores Endócrinos/análise , Humanos , Obesidade/metabolismo , Obesidade/fisiopatologia , Fenóis/análise , Medição de Risco , Fatores de Risco
8.
Anal Bioanal Chem ; 411(25): 6767-6775, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31420710

RESUMO

Nonylphenols (NP) are ubiquitous in the environment and show toxic effects and estrogenic activity. According to the corresponding framework directive in the field of water quality, isomers of NP (including 4-n-NP and branched 4-NP) are classified as priority hazardous substances and are regulated as a group of chain and ring isomers with a maximum acceptable concentration of 2 µg/L in inland and other surface waters. This study presents a new sensitive and innovative screening approach for estrogen active NP based on high-performance thin-layer chromatography. NP were focused in a single target zone on thin-layer plates by planar solid phase extraction (pSPE) and detected by a planar yeast estrogen screen (pYES) on the basis of their estrogenic activity. The mean limits of detection and quantitation were 14 and 26 ng per zone, respectively. After liquid-liquid extraction of water samples with dichloromethane, the mean recovery was close to 100% (relative standard deviation of 21% or less), and estrogen active NP were detectable down to 1 µg/L. Thus, pSPE-pYES provides both the detection and the quantitation of estrogenic NP in surface waters at the maximum acceptable concentration. Application of the approach on extracts of surface waters showed the use of pSPE-pYES for environmental samples, and no complex and time-consuming clean-up of the extracts was required. Estrogenic NP were not detectable in any of the investigated surface waters by means of the screening approach presented.


Assuntos
Disruptores Endócrinos/análise , Fenóis/análise , Poluentes Químicos da Água/análise , Cromatografia em Camada Delgada/métodos , Disruptores Endócrinos/efeitos adversos , Monitoramento Ambiental/métodos , Fenóis/efeitos adversos , Extração em Fase Sólida/métodos , Água/análise , Poluentes Químicos da Água/efeitos adversos , Leveduras/efeitos dos fármacos
9.
Toxicol Ind Health ; 35(7): 466-481, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31364507

RESUMO

The present study was conducted to investigate the antioxidant, histomorphometric, histochemical, immunohistochemical, biochemical, and cytological effects of coenzyme Q10 (CoQ10) against bisphenol-A (BPA)-induced testicular toxicity in rats. A total of 40 adult male Wistar rats were divided into five equal groups. The control group remained untreated. The vehicle control group was administered corn oil (2 ml/kg/day), the BPA group was given BPA (100 mg/kg/day), the CoQ10 group was supplemented with CoQ10 (10 mg/kg/day), and the rats in the CoQ10-BPA group received CoQ10 (10 mg/kg/day) followed by BPA (100 mg/kg/day) 1 h later. The treatments were administered by oral gavage for 14 days. Results showed that the seminiferous tubule diameters (STDs) and seminiferous epithelium heights (SEHs) at stages VII-VIII and XII-XIV, number of undifferentiated embryonic cell transcription factor-1 (UTF-1) positive cells per tubule, UTF-1 positive tubules (%), plasma glutathione (GSH), and serum superoxide dismutase activities, testicular GSH activity and sperm viability (%) decreased whereas the number of terminal dUTP nick end labeling (TUNEL) positive cells per tubule, TUNEL positive tubules (%), testicular and serum malondialdehyde (MDA) levels, and the rate of mid-piece sperm abnormality increased in the BPA administered group. However, while the STDs at stages VII-VIII and XII-XIV, SEHs at stages VII-VIII, plasma GSH, and serum SOD activities increased, serum MDA level decreased in the CoQ10-BPA group. In conclusion, these results suggest a protective effect of CoQ10 against BPA-induced testicular toxicity in rats.


Assuntos
Compostos Benzidrílicos/efeitos adversos , Fenóis/efeitos adversos , Testículo/efeitos dos fármacos , Testículo/patologia , Ubiquinona/análogos & derivados , Animais , Glutationa/metabolismo , Masculino , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo , Fatores de Transcrição/biossíntese , Ubiquinona/administração & dosagem , Ubiquinona/farmacologia
10.
Biomed Pharmacother ; 117: 109182, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31387175

RESUMO

Bisphenol A (BPA), a widely used industrial compound worldwide, was recently classified as an environmental toxicant. The intestines and liver are responsible for detoxification in humans and animals, and functional damage to these organs adversely affects the health of the body. However, the effect of BPA on intestinal and liver function remains unclear. In this study, we investigated the effects of dietary BPA uptake on oxidative stress, inflammatory response, apoptosis and mitochondrial function in the colons and livers of mice. Dietary BPA uptake significantly reduced the body weights of mice as well as their colon and liver weights. Dietary BPA uptake increased the levels of oxidative stress indicators such as reactive oxygen species, reactive nitrogen species, malondialdehyde and hydrogen peroxide in mouse serum, colon and liver tissues. Antioxidant indicators, such as superoxide dismutase, glutathione peroxidase, catalase and total antioxidant capacity, as well as proinflammatory cytokines (interleukin-1ß, interleukin-6, interleukin-8 and tumor necrosis factor-α) were also significantly reduced in the serum, colon, and liver tissues in the BPA group. Moreover, mitochondria-encoded genes and mitochondrial copy numbers were significantly reduced in the colon and liver tissues of the BPA mice. Dietary BPA uptake also increased gene abundance and enzyme activity of caspase-3, -8, -9 and -10. Our study found that dietary BPA induced oxidative stress, inflammatory response, apoptosis and mitochondrial dysfunction in mouse colons and livers.


Assuntos
Apoptose/efeitos dos fármacos , Compostos Benzidrílicos/efeitos adversos , Colo/efeitos dos fármacos , Inflamação/induzido quimicamente , Fígado/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Fenóis/efeitos adversos , Animais , Antioxidantes/metabolismo , Catalase/metabolismo , Colo/metabolismo , Glutationa Peroxidase/metabolismo , Inflamação/metabolismo , Fígado/metabolismo , Masculino , Malondialdeído/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Mitocôndrias/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo
11.
J Perinat Med ; 47(7): 765-770, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31348763

RESUMO

Background Bisphenol A (BPA) is an estrogenic, endocrine-disrupting compound widely used in the industry. It is also a ubiquitous environmental pollutant. Its presence was confirmed in human fetuses, which results from maternal exposure during pregnancy. The mechanisms behind maternal-fetal transfer, and relationships between pregnant women and fetal exposures remain unclear. The aim of this study was to assess the impact of maternal exposure to BPA on the exposure of the fetus. Methods Maternal plasma and amniotic fluid samples were collected from 52 pregnant women undergoing amniocentesis for prenatal diagnosis of chromosomal abnormalities. BPA was measured by gas chromatography-mass spectrometry (GC-MS). The permeability factor - a ratio of fetal-to-maternal BPA concentration - was used as a measure delineating the transplacental transfer of BPA. Results The median concentration of maternal plasma BPA was 8 times higher than the total BPA concentration in the amniotic fluid (8.69 ng/mL, range: 4.3 ng/mL-55.3 ng/mL vs. median 1.03 ng/mL, range: 0.3 ng/mL-10.1 ng/mL). There was no direct relationship between the levels of BPA in maternal plasma and amniotic fluid levels. The permeability factor, in turn, negatively correlated with fetal development (birth weight) (R = -0.54, P < 0.001). Conclusion Our results suggest that the risk of fetal BPA exposure depends on placental BPA permeability rather than the levels of maternal BPA plasma concentration and support general recommendations to become aware and avoid BPA-containing products.


Assuntos
Líquido Amniótico/química , Compostos Benzidrílicos , Peso ao Nascer/efeitos dos fármacos , Troca Materno-Fetal , Fenóis , Placenta , Adulto , Poluentes Ocupacionais do Ar/efeitos adversos , Poluentes Ocupacionais do Ar/sangue , Poluentes Ocupacionais do Ar/química , Compostos Benzidrílicos/efeitos adversos , Compostos Benzidrílicos/sangue , Compostos Benzidrílicos/química , Exposição Ambiental/prevenção & controle , Estrogênios não Esteroides/efeitos adversos , Estrogênios não Esteroides/sangue , Estrogênios não Esteroides/química , Feminino , Cromatografia Gasosa-Espectrometria de Massas/métodos , Humanos , Exposição Materna/prevenção & controle , Permeabilidade , Fenóis/efeitos adversos , Fenóis/sangue , Fenóis/química , Placenta/metabolismo , Placenta/fisiopatologia , Gravidez , Segundo Trimestre da Gravidez
12.
J Toxicol Sci ; 44(7): 481-491, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31270304

RESUMO

Bisphenol A (BPA), an environmental chemical to which humans are commonly exposed, has been shown to increase cholesterol level but the molecular mechanism is not clear. Since cholesterol biosynthesis plays an important role in elevating cholesterol level, the aim of the present study is to explore the effects of BPA on cholesterol biosynthesis in HepG2 cells and its possible mechanisms. HepG2 cells were treated with different concentrations of BPA for 24 hr, the total cholesterol level and the activity of 3-Hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) were measured using commercial enzymatic assay kits, and the mRNA and protein expression levels of sterol regulatory element binding protein-2(SREBP-2) and HMGCR were analyzed by qPCR, Western blotting and immunofluorescence, respectively. After treating HepG2 cells with different concentrations (0.1 nM~10 µM) of BPA for 24 hr, we found that BPA at the environmentally relevant concentrations of 1 nM and 10 nM significantly increased the total cholesterol content, the activity and expression of HMGCR in HepG2 cells, but at 100 nM, 1 µM and 10 µM doses, BPA had no stimulatory effect on cholesterol biosynthesis. The whole dose-response relationship follows non-monotonic dose responses, such as an inverted U-shape. Using human SREBP-2 small interfering RNA, we further discovered that the stimulatory effects of BPA on cholesterol biosynthesis and HMGCR expression could be prevented by blockade of the SREBP-2 pathway. This study provides important implications for understanding the potential lipotoxicity of BPA exposure, and it also indicates that low-dose BPA induces hepatic cholesterol biosynthesis through upregulating the SREBP-2/HMGCR signaling pathway.


Assuntos
Compostos Benzidrílicos/efeitos adversos , Colesterol/biossíntese , Hidroximetilglutaril-CoA Redutases/metabolismo , Fenóis/efeitos adversos , Plastificantes/efeitos adversos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Proteína de Ligação a Elemento Regulador de Esterol 2/metabolismo , Relação Dose-Resposta a Droga , Células Hep G2 , Humanos , Estimulação Química , Regulação para Cima/efeitos dos fármacos
13.
Chemosphere ; 236: 124314, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31310970

RESUMO

In the past few decades, environmental pollutants have become common because of misused nonionic surfactants and detergents. Nonylphenol ethoxylates (NPs) are one of the most important contaminants of water. Therefore, the present study aimed to investigate the protective blocking effect of apoptosis (deficient P53 gene) on 4-nonylphenol (4-NP)-induced nephrotoxicity of medaka (Oryzias latipes). We divided 36 fish into six groups: two different control groups of wild type (Wt; Hd-rR) control and p53 (-/-) control, and four different treated with 4-nonylphenol (50 µg/L and 100 µg/L) for 15 days. Histology, immunochemistry, and TUNEL assays confirmed that 4-NP causes nephrotoxicity. Our results showed that 4-NP administration significantly disturbed the kidney structure and function and 4-NP-treated fish showed dilated glomerular vessels, had less glomerular cellular content, decreased expression of glomerular proteins, and an increased level of apoptosis compared with a Wt control group (P < 0.05). As p53 is an apoptotic inducer, some protection in p53-deficient medaka was found as nephrotoxic effects of 4-NP were minimized significantly. Our study demonstrated for the first time to our knowledge that 4-NP induces apoptosis, causing nephrotoxicity in medaka. We found that blocking apoptosis blocking was able to protect the kidney from the toxic effects of 4-NP.


Assuntos
Nefropatias/induzido quimicamente , Fenóis/efeitos adversos , Proteína Supressora de Tumor p53/metabolismo , Animais , Oryzias
14.
J Perinat Med ; 47(7): 741-749, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31339859

RESUMO

Background Bisphenol-A (BPA) is a widespread pollutant whose effects on pregnant women are poorly understood. Therefore, we investigated the effects of BPA on basal and bacteria-stimulated production of proinflammatory cytokines [interleukin (IL)-1ß, tumor necrosis factor-α (TNF-α) and IL-6], anti-inflammatory mediators [soluble glycoprotein 130 (sgp) 130, heme oxidase-1 (HO-1) and IL-10] and biomarkers for neurodevelopment [brain-derived neurotrophic factor (BDNF)], and oxidative stress [8-isoprostane (8-IsoP)] by the placenta. Methods Placental explant cultures were treated with BPA (0-10,000 nM) in the presence or absence of 107 colony-forming unit (CFU)/mL heat-killed Escherichia coli for 24 h. Biomarker concentrations in conditioned medium were quantified by the enzyme-linked immunosorbent assay (ELISA). Results Under basal conditions, IL-1ß and IL-6 production was enhanced by BPA in a dose-dependent manner. Sgp130, a soluble receptor that reduces IL-6 bioactivity, was suppressed by BPA at 1000-10,000 nM. BPA also enhanced BDNF production at 1000 and 10,000 nM, and 8-IsoP expression at 10 and 100 nM. For bacteria-treated cultures, BPA increased IL-6 production at 100 nM and reduced sgp130 at 1000 nM but had no effect on IL-1ß, TNF-α, BDNF, HO-1, 8-IsoP or IL-10 production. Conclusion BPA may increase placental inflammation by promoting IL-1ß and IL-6 but inhibiting sgp130. It may also disrupt oxidative balance and neurodevelopment by increasing 8-IsoP and BDNF production.


Assuntos
Compostos Benzidrílicos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Citocinas , Escherichia coli/crescimento & desenvolvimento , Inflamação , Fenóis , Placenta , Poluentes Ocupacionais do Ar/efeitos adversos , Poluentes Ocupacionais do Ar/metabolismo , Compostos Benzidrílicos/efeitos adversos , Compostos Benzidrílicos/metabolismo , Biomarcadores/metabolismo , Contagem de Colônia Microbiana/métodos , Citocinas/classificação , Citocinas/metabolismo , Estrogênios não Esteroides/efeitos adversos , Estrogênios não Esteroides/metabolismo , Feminino , Humanos , Inflamação/induzido quimicamente , Inflamação/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fenóis/efeitos adversos , Fenóis/metabolismo , Placenta/efeitos dos fármacos , Placenta/imunologia , Placenta/metabolismo , Gravidez
15.
Ecotoxicology ; 28(7): 732-743, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31250287

RESUMO

HHCB [1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta(g)-2-benzopyran] and 4-tert-octylphenol [4-(1,1,3,3-tetramethylbutyl)phenol] are widely used emerging contaminants that have the potential to cause adverse effects in the environment. The purpose of this study was to observe if and how environmentally realistic concentrations of these contaminants alter growth in plant populations. It was hypothesized that within an exposed Gypsophila elegans Bieb (annual baby's breath) population especially fast-growing seedlings are impaired even when the population mean is unaffected, and small doses can cause hormesis and, thus, an increase in shoot or root length. In a dose-response experiment, an experimental population of G. elegans was established (total 15.600 seeds, 50 seeds per replicate, 24 replicates per concentration, 5.2 seedlings/cm2) and exposed to 12 doses of HHCB or 4-tert-octylphenol. After five days, shoot and root length values were measured and population averages, as well as slow- and fast-growing subpopulations, were compared with unexposed controls. Growth responses were predominantly monophasic. HHCB seemed to selectively inhibit both root and shoot elongation among slow- and fast-growing individuals, while 4-tert-octylphenol selectively inhibited both root and shoot elongation of mainly fast-growing seedlings. The ED50 values (dose causing 50% inhibition) revealed that the slow-growing seedlings were more sensitive and fast-growing seedlings less sensitive than the average of all individuals. Although there was toxicant specific variation between the effects, selective toxicity was consistently found among both slow- and fast-growing plants starting already at concentrations of 0.0067 µM, that are usually considered to be harmless. This study indicates that these contaminants can change size distribution of a plant population at low concentrations in the nM/µM range.


Assuntos
Benzopiranos/efeitos adversos , Caryophyllaceae/efeitos dos fármacos , Hormese/efeitos dos fármacos , Fenóis/efeitos adversos , Poluentes do Solo/efeitos adversos , Caryophyllaceae/crescimento & desenvolvimento , Relação Dose-Resposta a Droga , Alemanha
16.
J Pharm Biomed Anal ; 172: 238-242, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31063881

RESUMO

Endocrine disrupting chemicals (EDCs) such as phthalates and bisphenol A (BPA) are substances that may interfere with the actions of endogenous hormones and may be associated with estrogen-related diseases such as endometriosis. This paper describes a case-control study to evaluate the relationship between endometriosis and phthalates and BPA exposure, through biomarkers analysis in urine. The biomarkers of exposure analyzed were metabolites mono-methyl phthalate, mono-isobutyl phthalate (MiBP), mono-butyl phthalate, mono-cyclohexyl phthalate, mono-(ethylhexyl) phthalate, mono-isononyl phthalate, mono-octyl phthalate (MOP), mono-benzyl phthalate and BPA. Urine samples were collected from women aged 18-45 years old. The Study group (n = 30) and Control group (n = 22) were composed of women using as criteria confirmation of endometriosis by videolaparoscopy surgery with histological diagnosis and the absence of the disease, respectively. The analytical method used liquid phase microextraction with determination by gas chromatography coupled to mass spectrometry. The concentrations of biomarkers were adjusted by the creatinine concentration in urine samples of the two groups. The values obtained for the Study Group were compared with the values obtained for the Control Group. The chi-square test and Odds Ratio were used to compare dichotomized phthalate metabolites and BPA metabolite by endometriosis. All nine metabolites were found in different concentrations in the urine samples in both groups The phthalate metabolites that had the highest concentrations, were MOP and MiBP, in which the values of 670 µg g-1 and 560 µg g-1, respectively. The relationship between endometriosis and the all grouped metabolites was evaluated, but was not statistically significant with a 95% CI [X2 (df = 1) = 1.471; p = 0.225]. However, odds ratio (95% confidence interval - CI) for MiBP, which was found at relatively high concentrations in the samples, by endometriosis was 1.929 (0.507-7.332). The food habits and gynecologic history were evaluated and no difference was found between groups. Although no evidences of causal link was found, this study contributes to show that other analysis must be done for evaluating the association between endometriosis and compounds suspected of being EDC.


Assuntos
Compostos Benzidrílicos/efeitos adversos , Endometriose/induzido quimicamente , Fenóis/efeitos adversos , Ácidos Ftálicos/efeitos adversos , Adolescente , Adulto , Biomarcadores/metabolismo , Estudos de Casos e Controles , Disruptores Endócrinos/efeitos adversos , Endometriose/metabolismo , Exposição Ambiental/efeitos adversos , Poluentes Ambientais/efeitos adversos , Estrogênios/metabolismo , Feminino , Cromatografia Gasosa-Espectrometria de Massas/métodos , Humanos , Pessoa de Meia-Idade , Adulto Jovem
17.
Environ Int ; 129: 59-67, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31121516

RESUMO

Bisphenol analogues including bisphenol A (BPA), bisphenol AF (BPAF), bisphenol F (BPF), and bisphenol S (BPS) share similar chemical structures and endocrine disrupting effects. Their effects on metabolisms, however, are so far only marginally understood. In this study, NMR-based metabonomic profiles of HepG2 cell culture media and PCR array were used to assess the metabolomics disturbances and gene expression levels of HepG2 in response to four BPs (BPA, BPAF, BPF, and BPS). The results indicated that BP analogues resulted in disturbances in 7-15 metabolites that were classified as amino acid (alanine, glutamine, glutamate), intermediates and end-products in the glycolysis (pyruvate) and the tricarboxylic acid cycle (acetate, lactate). Their rank in order according to the number of metabolites and pathways was BPF > BPA > BPAF > BPS. The common disrupted pathways (pyruvate metabolism; alanine, aspartate, and glutamate metabolism) indicated enhanced glycolysis. The following glucometabolic PCR array analysis suggested that although four BPs shared the capability of disrupting glucose metabolism, they may act through different mechanisms: BPAF has increased the pyruvate kinase (PKLR) expression level, which implied enhanced glycolysis that was agreed with NMR results. The other three BP analogues, however, decreased the expression level of glucokinase (GCK) that indicated glucose sensing impairment. Our results demonstrated the potential for using metabolomic and PCR array to understand the underlying action of mechanisms and identify the potential targets for future targeted risk assessment.


Assuntos
Compostos Benzidrílicos/efeitos adversos , Disruptores Endócrinos/efeitos adversos , Poluentes Ambientais/efeitos adversos , Metaboloma/efeitos dos fármacos , Fenóis/efeitos adversos , Sulfonas/efeitos adversos , Transcriptoma/efeitos dos fármacos , Células Hep G2 , Humanos
19.
Biomed Res Int ; 2019: 8939854, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31111071

RESUMO

Sweet potato (Ipomoea batatas L. Lam.), known as "Shakarqandi" in Pakistan, is an imperative root vegetable with large size, traditionally used as aphrodisiac, antiprostatic, anti-inflammatory, antidiabetic, cardiotonic, and anticancer agent. Present study was conducted to gauge aphrodisiac potential of Ipomoea batatas ethyl acetate (IPT-EA, IPA-EA) and methanol (IPT-M, IPA-M) extracts from tuber and aerial part, respectively, via behavioral and biochemical tests and their possible protective role in BPA-induced gonadotoxicity at the dose 300 mg/kg in male Sprague Dawley rats. Phytochemical analysis was done qualitatively and quantitatively through total phenolic and flavonoid content (TPC and TFC) and high performance liquid chromatographic (HPLC-DAD) fingerprinting while antioxidant profiling used multimode in vitro assays. To calculate sexual excitement mount latency, intromission latency, mount frequency, intromission frequency, ejaculatory latency, and postejaculatory interval were examined while for biochemical ratification semen characteristics, levels of testosterone, follicle stimulating hormone (FSH), luteinizing hormone (LH), and estradiol were measured. Gonadoprotective ability was assessed through comet assay and histomorphological examination of testes. Qualitative analysis ensured the presence of phenols, flavonoids, tannins, anthocyanin, saponins, coumarins, terpenoids, and betacyanin. Quantitatively maximal TPC (304.32±7.20 µg GAE/mg dry extract) and TFC (214.77±4.09 µg QE/mg DE) were estimated in IPA-EA extract. IPT-EA yielded maximum rutin (7.3±0.12) and myricetin (2.7±0.14 µg/mg DE) while IPA-EA and IPA-M yielded maximum caffeic acid (4.05±0.22 and 1.92±0.17 µg/mg DE, respectively) in HPLC-DAD analysis. Extracts enhanced sexual excitement, improved semen quality, levels of testosterone, FSH, LH, and estradiol, and successfully attenuated toxic effects of BPA. Levels of endogenous antioxidant enzymes (CAT, SOD, POD, and GSH) were restored and NO abundance was minimized. Significant stimulation in sexual behavior, amelioration of toxicity symptoms, elevated spermatic production, raised viability, vitalized levels of gonadal hormones, maintained endogenous enzymes, genoprotection, and reformed testicular histology endorsed I. batatas as a better aphrodisiac alternative and gonadoprotective agent.


Assuntos
Afrodisíacos/farmacologia , Compostos Benzidrílicos/efeitos adversos , Ipomoea batatas/química , Medicina Tradicional/métodos , Fenóis/efeitos adversos , Extratos Vegetais/farmacologia , Testículo/efeitos dos fármacos , Animais , Antioxidantes/química , Comportamento Animal , Cromatografia Líquida de Alta Pressão , Feminino , Flavonoides/química , Hormônios Gonadais , Masculino , Modelos Animais , Paquistão , Fenóis/química , Compostos Fitoquímicos/farmacologia , Tubérculos/química , Ratos , Ratos Sprague-Dawley , Análise do Sêmen , Comportamento Sexual Animal/efeitos dos fármacos , Disfunções Sexuais Fisiológicas/tratamento farmacológico , Testículo/patologia
20.
Drug Dev Res ; 80(5): 666-679, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31112325

RESUMO

Inflammation is the response of the body to noxious stimuli such as infections, trauma, or injury. Experimental studies have shown that vanillic acid has anti-inflammatory effects. The objective of this study was to investigate the anti-inflammatory and antipyretic properties of the derivative of vanillic acid, isopropyl vanillate (ISP-VT), in mice. The results of this study indicated that ISP-VT reduced paw edema induced by carrageenan, dextran sulfate (DEX), compound 48/80, serotonin, bradykinin (BK), histamine (HIST), and prostaglandin E2 (PGE2). Furthermore, ISP-VT reduced recruitment of leukocytes and neutrophils and reduced its adhesion and rolling, and decreased myeloperoxidase enzyme activity (MPO), cytokine levels (tumor necrosis factor-α and interleukin-6), and vascular permeability. ISP-VT also significantly reduced the expression of cyclooxygenase-2 (COX-2) in subplantar tissue of mice. ISP-VT inhibited COX-2 selectively compared to the standard drug. Our results showed that although ISP-VT binds to COX-1, it is less toxic than indomethacin, as evidenced by MPO analysis of gastric tissue. Treatment with the ISP-VT significantly reduced rectal temperature in yeast-induced hyperthermia in mice. Our results showed that the main mechanism ISP-VT-induced anti-inflammatory activity is by inhibition of COX-2. In conclusion, our results indicate that ISP-VT has potential as an anti-inflammatory and antipyretic therapeutic compound.


Assuntos
Anti-Inflamatórios/administração & dosagem , Carragenina/efeitos adversos , Inibidores de Ciclo-Oxigenase/administração & dosagem , Inflamação/tratamento farmacológico , Fenóis/efeitos adversos , Ácido Vanílico/química , Animais , Anti-Inflamatórios/síntese química , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Anticorpos Monoclonais/efeitos dos fármacos , Inibidores de Ciclo-Oxigenase/síntese química , Inibidores de Ciclo-Oxigenase/química , Inibidores de Ciclo-Oxigenase/farmacologia , Modelos Animais de Doenças , Feminino , Inflamação/induzido quimicamente , Inflamação/metabolismo , Injeções Intraperitoneais , Masculino , Camundongos , Modelos Moleculares , Fenóis/síntese química , Fenóis/química , Fenóis/farmacologia , Bibliotecas de Moléculas Pequenas/administração & dosagem , Bibliotecas de Moléculas Pequenas/síntese química , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/farmacologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA