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1.
Int J Mol Sci ; 22(5)2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33802611

RESUMO

The objective of this work has been to characterize the estrogenic activity of bisphenol-A (BPA) and the adverse effects on the endocannabinoid system (ECS) in modulating germ cell progression. Male offspring exposed to BPA during the foetal-perinatal period at doses below the no-observed-adverse-effect-level were used to investigate the exposure effects in adulthood. Results showed that BPA accumulates specifically in epididymal fat rather than in abdominal fat and targets testicular expression of 3ß-hydroxysteroid dehydrogenase and cytochrome P450 aromatase, thus promoting sustained increase of estrogens and a decrease of testosterone. The exposure to BPA affects the expression levels of some ECS components, namely type-1 (CB1) and type-2 cannabinoid (CB2) receptor and monoacylglycerol-lipase (MAGL). Furthermore, it affects the temporal progression of germ cells reported to be responsive to ECS and promotes epithelial germ cell exfoliation. In particular, it increases the germ cell content (i.e., spermatogonia while reducing spermatocytes and spermatids), accelerates progression of spermatocytes and spermatids, promotes epithelial detachment of round and condensed spermatids and interferes with expression of cell-cell junction genes (i.e., zonula occcludens protein-1, vimentin and ß-catenin). Altogether, our study provides evidence that early exposure to BPA produces in adulthood sustained and site-specific BPA accumulation in epididymal fat, becoming a risk factor for the reproductive endocrine pathways associated to ECS.


Assuntos
Tecido Adiposo/efeitos dos fármacos , Compostos Benzidrílicos/efeitos adversos , Compostos Benzidrílicos/metabolismo , Endocanabinoides/metabolismo , Epididimo/efeitos dos fármacos , Estrogênios/metabolismo , Células Germinativas/efeitos dos fármacos , Fenóis/efeitos adversos , Fenóis/metabolismo , Tecido Adiposo/metabolismo , Animais , Sistema Endócrino/efeitos dos fármacos , Sistema Endócrino/metabolismo , Epididimo/metabolismo , Epitélio/efeitos dos fármacos , Epitélio/metabolismo , Células Germinativas/metabolismo , Junções Intercelulares/efeitos dos fármacos , Junções Intercelulares/metabolismo , Masculino , Camundongos , Fatores de Risco , Testosterona/metabolismo
2.
Environ Int ; 150: 106433, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33637302

RESUMO

BACKGROUND: Experimental evidence demonstrates that exposure to bisphenol A (BPA), and the recently introduced alternatives bisphenol S (BPS) and bisphenol F (BPF) alter normal neurodevelopment. More research is needed to evaluate the associations between exposure to individual BPA alternatives and neurodevelopmental outcomes in humans. OBJECTIVE: The present study aimed at examining the individual associations between prenatal BPA, BPS and BPF exposure and cognitive outcomes in children at age 7 years. METHOD: Women were enrolled in the Swedish Environmental Longitudinal Mother and Child, Asthma and Allergy (SELMA) study, at gestational median week 10.0, and their children were examined for cognitive function at 7 years of age (N = 803). Maternal urinary BPA, BPS, and BPF concentrations were measured at enrollment and childrens cognitive function at the age of 7 years was measured using the Wechsler Intelligence Scale for Children IV (WISC-IV). RESULTS: All three bisphenols were detected in over 90% of the women, where BPA had the highest geometric mean concentrations (1.55 ng/mL), followed by BPF (0.16 ng/mL) and BPS (0.07 ng/mL). Prenatal BPF exposure was associated with decreased full scale IQ (ß = -1.96, 95%CI; -3.12; -0.80), as well as with a decrease in all four sub scales covering verbal comprehension, perceptual reasoning, working memory and processing speed. This association corresponded to a 1.6-point lower IQ score for an inter-quartile-range (IQR) change in prenatal BPF exposure (IQR = 0.054-0.350 ng/mL). In sex-stratified analyses, significant associations with full scale IQ were found for boys (ß = -2.86, 95%CI; -4.54; -1.18), while the associations for girls did not reach significance (ß = -1.38, 95%CI; -2.97; 0.22). No significant associations between BPA nor BPS and cognition were found. DISCUSSION: Prenatal exposure to BPF was significantly associated with childrens cognitive function at 7 years. Since BPF is replacing BPA in numerous consumer products globally, this finding urgently call for further studies.


Assuntos
Compostos Benzidrílicos/efeitos adversos , Cognição/efeitos dos fármacos , Fenóis/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal , Criança , Feminino , Humanos , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Suécia
3.
Phytother Res ; 35(4): 2005-2024, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33315269

RESUMO

The underlying mechanisms of bisphenol A (BPA)-induced metabolic disorder and the protective impact of Nigella sativa oil (NSO) and thymoquinone (TQ) against BPA-induced metabolic disorder were investigated. Rats were treated as follows: Control, BPA (10 mg/kg), TQ (2 mg/kg), NSO (84 µL/kg), BPA + TQ (0.5, 1, 2 mg/kg), and BPA + NSO (21, 42, 84 µL/kg). BPA was administered by gavage, while, TQ and NSO were injected intraperitoneally (daily, 54 days). The weight, blood pressure, serum parameters [glucose, lipid profile, hepatic enzymes, insulin, interlukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), leptin, adiponectin], malondialdehyde (MDA), glutathione (GSH) and insulin signaling pathways [insulin receptor substrate (p-IRS,IRS); kinase (p-Akt,Akt); glycogen synthase kinase (p-GS3K,GS3K)] were measured. BPA increased the blood pressure, MDA, lipid profile, hepatic enzymes, insulin, IL-6, TNF-α, and leptin, and decreased the GSH and phosphorylated forms of IRS, Akt, GS3K but did not alter weight, glucose, IRS, AKT, and GS3K in the liver. Administration of NSO or TQ with BPA reduced the blood pressure, liver level of MDA, lipid profile, hepatic enzymes, insulin, IL-6, TNF-α, leptin, and increased the liver level of GSH and p-IRS, p-AKT, p-GS3K. TQ and NSO are thought to be effective in controlling metabolic disorders induced by BPA.


Assuntos
Compostos Benzidrílicos/efeitos adversos , Benzoquinonas/química , Doenças Metabólicas/induzido quimicamente , Doenças Metabólicas/tratamento farmacológico , Nigella sativa/química , Fenóis/efeitos adversos , Animais , Humanos , Masculino , Projetos Piloto , Ratos , Ratos Wistar
4.
Medicine (Baltimore) ; 99(45): e23067, 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33157965

RESUMO

Bisphenol A (BPA) is a well-known endocrine-disrupting chemical which can cause potential health risks and interfere with thyroid hormones through multiple avenues. This study aimed to evaluate the hotspots and emerging trends on BPA and thyroid hormones by using a bibliometric method.Publications related on BPA and thyroid hormones were downloaded from Science Citation Index-Expanded database. Annual outputs, high yield journals, countries, institutions, authors and their cited times were summarized. In addition, keywords co-occurrence, burst references and citation networks were bibliometric analyzed.From 2000 to 2019, 418 articles were published. Both of the Environment International and Environmental Health Perspectives, United States, Chinese Academy of Sciences and Antonia M. Calafat were the most recorded journals, countries, institutions and authors, respectively. The main research area was Toxicology. In addition of the retrieve term "bisphenol-a" and "thyroid-hormone", "in-vitro", "exposure" and "endocrine disruptors", were the hotspot keywords and "triclosan", "oxidative stress" and "united-states" were the most recent trends keywords. "Thyroid hormone action is disrupted by Bisphenol A as an antagonist" published on The Journal of Clinical Endocrinology & Metabolism by Kenji Moriyama in 2002 got both the highest burst score and citation score. Six groups were clustered and the mechanism of BPA's effect on thyroid hormones, and the exposure of BPA and potential risks in children and pregnant women were the two main large fields.The number of publications in the field of BPA and thyroid hormones has increased tremendously since 2000. The research hotspot ranged from mechanism researches in animal models to epidemiological studies. "Thyroid hormone action is disrupted by bisphenol A as an antagonist" of Kenji Moriyama provided important building blocks in the field. The impact of BPA on thyroid hormones, especially pregnant women and children, was the latest research frontiers and might be the future direction of this filed in the following years.


Assuntos
Compostos Benzidrílicos/efeitos adversos , Depuradores de Radicais Livres/efeitos adversos , Fenóis/efeitos adversos , Publicações/estatística & dados numéricos , Hormônios Tireóideos/metabolismo , Animais , Compostos Benzidrílicos/farmacologia , Bibliometria , Criança , Gerenciamento de Dados , Disruptores Endócrinos/efeitos adversos , Disruptores Endócrinos/farmacologia , Feminino , Depuradores de Radicais Livres/farmacologia , Humanos , Modelos Animais , Fenóis/farmacologia , Gravidez , Tiroxina/efeitos dos fármacos , Tri-Iodotironina/efeitos dos fármacos
5.
Environ Health ; 19(1): 93, 2020 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-32867778

RESUMO

BACKGROUND: Bisphenol A (BPA), one of the highest-volume chemicals produced worldwide, has been identified as an endocrine disruptor. Many peer-reviewing studies have reported adverse effects of low dose BPA exposure, particularly during perinatal period (gestation and/or lactation). We previously demonstrated that perinatal oral exposure to BPA (via gavage of mothers during gestation and lactation) has long-term consequences on immune response and intestinal barrier functions. Due to its adverse effects on several developmental and physiological processes, BPA was removed from consumer products and replaced by chemical substitutes such as BPS or BPF, that are structurally similar and not well studied compare to BPA. Here, we aimed to compare perinatal oral exposure to these bisphenols (BPs) at two doses (5 and 50 µg/kg of body weight (BW)/day (d)) on immune response at intestinal and systemic levels in female offspring mice at adulthood (Post Natal Day PND70). METHODS: Pregnant female mice were orally exposed to BPA, BPS or BPF at 5 or 50 µg/kg BW/d from 15th day of gravidity to weaning of pups at Post-Natal Day (PND) 21. Humoral and cellular immune responses of adult offspring (PND70) were analysed at intestinal and systemic levels. RESULTS: In female offspring, perinatal oral BP exposure led to adverse effects on intestinal and systemic immune response that were dependant of the BP nature (A, S or F) and dose of exposure. Stronger impacts were observed with BPS at the dose of 5 µg/kg BW/d on inflammatory markers in feces associated with an increase of anti-E. coli IgG in plasma. BPA and BPF exposure induced prominent changes at low dose in offspring mice, in term of intestinal and systemic immune responses, provoking an intestinal and systemic Th1/Th17 inflammation. CONCLUSION: These findings provide, for the first time, results of long-time consequences of BPA, S and F perinatal exposure by oral route on immune response in offspring mice. This work warns that it is mandatory to consider immune markers and dose exposure in risk assessment associated to new BPA's alternatives.


Assuntos
Compostos Benzidrílicos/efeitos adversos , Disruptores Endócrinos/efeitos adversos , Imunidade Celular/efeitos dos fármacos , Imunidade Humoral/efeitos dos fármacos , Fenóis/efeitos adversos , Sulfonas/efeitos adversos , Administração Oral , Animais , Relação Dose-Resposta a Droga , Feminino , Intestinos/efeitos dos fármacos , Intestinos/imunologia , Lactação/efeitos dos fármacos , Exposição Materna , Camundongos , Camundongos Endogâmicos C3H , Gravidez/efeitos dos fármacos
7.
Sci Rep ; 10(1): 5882, 2020 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-32246001

RESUMO

This study aimed to examine the impact of BPA exposure on pregnancy and foetuses on cardiac tissues and the expression of cardiac microRNAs (miRNAs) related to heart development and diseases. Pregnancy is known to be the "critical windows" in determining the offspring physical and cells development in their life after birth. The increment of the risk of cardiovascular disease (CVD) in a later stage of life has been reported by few studies demonstrated from prenatal exposure of BPA. BPA has been shown to alter miRNAs expression profiles for organ development, regeneration and metabolic functions. These alterations have been associated with the risk of CVDs. However, the associations between pregnancy outcomes and miRNAs expression in cardiac of mother- and foetuses-exposed to BPA are still not entirely explored. In BPA-exposed pregnant rat groups, a significant weight gained was observed in comparison to control (p < 0.05). Interestingly, significant changes in systolic and diastolic blood pressure between the first and third trimester of BPA-exposed pregnant rats were also observed (p < 0.05). In BPA-exposed pregnant rats, miR-499-5p was significantly altered in the heart (p < 0.01). Meanwhile, altered miR-17-5p, -208-3p, and -210-3p expressions were observed in all heart of the foetuses from BPA-exposed pregnant rats (p < 0.05). In H&E staining, BPA-exposed foetal hearts showed a sign of fibrosis while BPA-exposed pregnant rats showed muscle remnant. Masson trichrome staining further confirmed the presence of fibrosis observed in BPA-exposed foetal heart and reduced expression of cardiac troponin I (cTnI) was also observed in BPA-exposed foetal heart. In summary, altered cardiac miRNAs with histological changes were observed in both mother- and foetus-exposed BPA These findings put forward the importance of future work to further understand how prenatal BPA exposure affect foetuses in their later stage of life.


Assuntos
Compostos Benzidrílicos/efeitos adversos , Coração/embriologia , MicroRNAs/metabolismo , Fenóis/efeitos adversos , Gravidez/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Útero/efeitos dos fármacos , Animais , Feminino , Imunofluorescência , Coração/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/embriologia , Fígado/patologia , Miocárdio/patologia , Reação em Cadeia da Polimerase , Ratos , Ratos Sprague-Dawley
8.
Nutr Metab Cardiovasc Dis ; 30(5): 768-776, 2020 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-32127337

RESUMO

BACKGROUND AND AIMS: Phenols and parabens are ubiquitous and have been associated with markers of cardiovascular health. However, the literature lacks population-based studies examining the link between these endocrine disruptors and diabetes. We examined the association between paraben/phenol concentrations and diabetes among a nationally representative sample of US adults. METHODS AND RESULTS: We utilized data from the 2005-2014 National Health and Nutrition Examination Surveys (N = 8498). Total urinary concentrations of BPA, triclosan, BP-3, and propyl, butyl, ethyl, and methyl parabens were measured from urine specimens collected during the examination session. Diabetes status was based on self-report of a previous diagnosis or HbA1c≥6.5%. We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CI) associated with the difference in log-transformed values of the 75th and 25th percentiles for each phenol/paraben, adjusting for potential confounders. The adjusted ORs (95% CI) of diabetes comparing the 75th to 25th percentiles of each paraben/phenol were 1.09 (0.96-1.23) for BPA, 0.84 (0.72-0.98) for triclosan, 0.69 (0.61-0.79) for BP-3, 0.71 (0.61-0.83) for propyl paraben, 0.66 (0.54-0.80) for butyl paraben, 0.60 (0.51-0.71) for ethyl paraben, and 0.79 (0.68-0.91) for methyl paraben. CONCLUSIONS: Higher concentrations of triclosan, BP-3, and propyl, butyl, ethyl, and methyl parabens were associated with lower odds of diabetes. These findings warrant further investigation into the potential mechanism behind the observed associations and the temporal direction of the associations, given that we cannot rule out reverse causation. Future studies of these endocrine disruptors may improve the understanding of their relationship with diabetes.


Assuntos
Diabetes Mellitus/epidemiologia , Diabetes Mellitus/urina , Disruptores Endócrinos/urina , Parabenos/metabolismo , Fenóis/urina , Biomarcadores/urina , Estudos Transversais , Diabetes Mellitus/diagnóstico , Disruptores Endócrinos/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Parabenos/efeitos adversos , Fenóis/efeitos adversos , Medição de Risco , Fatores de Risco , Estados Unidos/epidemiologia
9.
Curr Hypertens Rep ; 22(3): 23, 2020 02 29.
Artigo em Inglês | MEDLINE | ID: mdl-32114652

RESUMO

PURPOSE OF REVIEW: Cardiovascular disease (CVD) is a non-subsiding disease that remains a leading cause of morbidity and mortality. CVD has been associated with endocrine disruptors, such as bisphenol A (BPA). This review critically summarizes existing findings on BPA and hypertension, with particular attention to genomic, non-genomic, molecular, and cellular mechanisms of action that render BPA as a cardiovascular estrogenic disruptor. RECENT FINDINGS: Owing to its similar estrogenic structure, BPA has been shown to affect various phenotypes that are regulated by the natural hormone, estrogen. Indeed, BPA has been shown to interact with estrogen receptors, located both in the cell membrane and in the cytoplasm/nucleus. Given that estrogen plays an important role in cardiovascular physiology, a contributing role for BPA in CVD would not be unexpected. Existing literature, though limited, established BPA as a source of disruption in cardiovascular health, particularly hypertension. However, effects of BPA are largely dependent on the dose, patient gender, tissue, and developmental stage of the exposed tissue/organ. Accumulating evidence argues for an adverse effect of BPA on blood pressure, with this effect being gender, dose, and time specific. Thus, comprehensive studies which take these factors and other parameters, like epigenetic factors, into account are warranted before a thorough understanding is at hand.


Assuntos
Compostos Benzidrílicos , Estrogênios , Hipertensão , Fenóis , Compostos Benzidrílicos/efeitos adversos , Estrogênios/fisiologia , Humanos , Hipertensão/induzido quimicamente , Fenóis/efeitos adversos
11.
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
12.
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
14.
Environ Int ; 134: 105328, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31778932

RESUMO

Bisphenol A (BPA) and its replacement analog, bisphenol S (BPS), have been proposed as environmental obesogen to disrupt the lipid metabolism through regulating peroxisome proliferator-activated receptor gamma (PPARγ) receptor. However, there is a dearth of information on whether this biological effect can occur in human macrophage, a cell type which closely interacts with adipocytes and hepatocytes to control lipid metabolism. Here, we for the first time investigate the activity of BPA and BPS on PPARγ pathway in human macrophages. The results demonstrated that BPA and BPS served as activators of PPARγ in human macrophage cell line, and significantly induced the expression of lipid metabolism-related genes, including fatty acid binding protein 4 (FABP4), cluster of differentiation 36 (CD36) and nuclear receptor subfamily 1 group H member 3 (NR1H3). In PPARγ knockout cells, expression of these genes was down-regulated, suggesting that these genes are dependent on PPARγ. The underlying mechanisms were further investigated using an in vivo mouse model, and the results confirmed the induction of PPARγ and its respective target genes in mice following exposure to BPA or BPS. Moreover, the observed alteration of PPARγ expression highly correlated with the disturbance of metabolism profiles in liver tissues as detected by 1H Nuclear Magnetic Resonance (NMR)-based metabonomics. Overall, this study provided the first evidence that BPA and BPS activated PPARγ and its target genes in human macrophages, and provided comprehensive information to confirm that BPA and BPS disturb the metabolism through targeting PPARγ via both in vitro assays and in vivo animal models.


Assuntos
Compostos Benzidrílicos/efeitos adversos , Macrófagos/efeitos dos fármacos , PPAR gama/metabolismo , Fenóis/efeitos adversos , Sulfonas/efeitos adversos , Animais , Antígenos CD36 , Células Cultivadas , Humanos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Receptores X do Fígado , Metabolômica , Camundongos
15.
Environ Sci Pollut Res Int ; 27(4): 4513-4519, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31773524

RESUMO

The epigenetic changes induced by environmental contaminants play important roles in the inheritance of male reproductive dysfunction. The present study investigated DNA methylation changes and some oxidative stress biomarkers induced by bisphenol A (BPA) in male offspring. A total number of 48 female albino rats were administered orally with 50 µg/kg of BPA/day during gestation and/or lactation periods. At postnatal day 60, the samples were collected from the male pups to assess the serum testosterone, malondialdehyde (MDA) level, superoxide dismutase (SOD), glutathione S-transferase, and glutathione peroxidase (GSH-Px) activities in testicular tissue. DNA methylation in both DNA (cytosine-5)-methyltransferase 3A and estrogen receptor alpha genes was detected by methylation-specific PCR. BPA exposure resulted in significant decrease in the anogenital distance, testis and epididymis weights, serum testosterone level, SOD, GST, and GSH-Px levels with significant increase in weaning body weight and the MDA level. Additionally, BPA caused marked hypermethylation within Dnmt3A and ER- ∝ genes promoter regions in the testis of rat male pups. Graphical abstract.


Assuntos
Compostos Benzidrílicos/efeitos adversos , Metilação de DNA , Fenóis/efeitos adversos , Animais , Compostos Benzidrílicos/química , Feminino , Masculino , Estresse Oxidativo , Fenóis/química , Gravidez , Ratos , Testículo
16.
Environ Int ; 134: 105304, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31726358

RESUMO

BACKGROUND: Bisphenol A (BPA) may cause some adverse effects on human health by mimicking estrogen activities. In vitro andanimalstudies have observed the non-monotonic associations between BPA and natural estrogens, but the evidence in human study is lacking, particularly at multiple points in time during pregnancy. OBJECTIVE: We aimed to examine the relationships between BPA and estrogens in the three trimesters among Chinese pregnant women and their gender variations. METHODS: This study included 851 participants from a birth cohort conducted in Wuhan, China between 2014 and 2015. We measured concentrations of BPA and three estrogens (estrone (E1), 17ß-estradiol (E2) and estriol (E3)) in urine samples collected in the three trimesters of pregnancy (mean for each visit: 13.0, 23.6, and 35.9 weeks' gestation). We calculated the estimated daily intakes using urinary BPA concentrations and compared them with the tolerable intake value to assess potential health risks. We used multivariate linear regression models stratified by trimester and gender to explore trimester-specific and gender-specific associations of BPA with E1, E2, and E3. RESULTS: We found the decreased levels of estrogens (ß < 0, P < 0.05) in the upper BPA quartiles over three trimesters, except for the elevated levels of E3 (ß = 0.20, 95% CI: 0.02, 0.38) in the highest BPA quartile in the 2nd trimester. There were significant non-linear associations (overall associations P < 0.05, non-linear associations P < 0.05) between BPA and E3 in the three trimesters. In the gender-stratified analysis, we observed significant negative relationships (ß < 0, P < 0.05) between BPA and E2 among mothers carrying male fetuses in the 1st trimester and significant associations between BPA and E3 among mothers carrying female fetuses in the 2nd trimester. However, we found no significant relationship between BPA and E2 among mothers carrying female fetuses over three trimesters. CONCLUSIONS: Our findings support experimental evidence of non-monotonic relationships between BPA and three major estrogens, even at low doses of BPA. Mothers delivering male fetuses may be more sensitive to E2 at early pregnancy, and those delivering female fetuses may be more susceptive to E3 at mid-pregnancy.


Assuntos
Compostos Benzidrílicos/efeitos adversos , Estradiol/urina , Estriol/urina , Estrona/urina , Fenóis/efeitos adversos , China , Estrogênios , Feminino , Humanos , Modelos Lineares , Masculino , Análise Multivariada , Gravidez , Trimestres da Gravidez
17.
Environ Pollut ; 259: 113779, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31887597

RESUMO

Many studies show that bisphenol A (BPA) is widespread in human breast milk. However, the occurrence of other bisphenol analogues (BPs), including bisphenol S (BPS), bisphenol F (BPF), and bisphenol AF (BPAF), in breast milk is still not well known. In this study, breast milk samples were collected from 190 women in Hangzhou, China, with the aims to characterize the occurrence of BPA, BPS, BPF, and BPAF in these samples and to investigate their effects on postnatal growth of infants through breast milk consumption. BPA (mean 2.5 ng/mL, range < LOD-15 ng/mL) was the most abundant BP in breast milk, followed by BPS (0.19 ng/mL,

Assuntos
Compostos Benzidrílicos/química , Desenvolvimento Infantil/efeitos dos fármacos , Leite Humano/química , Fenóis/efeitos adversos , Adulto , Compostos Benzidrílicos/administração & dosagem , Compostos Benzidrílicos/efeitos adversos , Compostos Benzidrílicos/análise , China , Feminino , Humanos , Lactente , Masculino , Fenóis/administração & dosagem , Cuidado Pós-Natal
18.
Rev Environ Health ; 35(2): 201-210, 2020 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-31743105

RESUMO

Bisphenol-A (BPA) is a synthetic chemical used in the manufacturing of polycarbonates and epoxy resins. This paper is a review of studies reporting the occurrences and concentrations of BPA in the environment and associated impact on human health. Studies have found that at high temperature conditions such as open burning of dumped waste in developing nations can relocate BPA from plastic waste into the environment. BPA is a proven endocrine disruptor capable of mimicking or blocking the receptors and altering hormone concentrations and its metabolism. Even though it is consumed in a low dose, it can stimulate cellular responses and affect body functions. Biomonitoring studies show that human and animal exposure to BPA is rapid and continuous. In-depth studies are needed to understand the fate of these compounds particularly in the developing nations and the associated adverse health impacts of BPA due to prolonged exposure.


Assuntos
Compostos Benzidrílicos/efeitos adversos , Disruptores Endócrinos/efeitos adversos , Exposição Ambiental/efeitos adversos , Fenóis/efeitos adversos , Animais , Humanos , Camundongos
19.
Annu Rev Physiol ; 82: 177-202, 2020 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-31738670

RESUMO

Endocrine disrupting chemicals are common in our environment and act on hormone systems and signaling pathways to alter physiological homeostasis. Gestational exposure can disrupt developmental programs, permanently altering tissues with impacts lasting into adulthood. The brain is a critical target for developmental endocrine disruption, resulting in altered neuroendocrine control of hormonal signaling, altered neurotransmitter control of nervous system function, and fundamental changes in behaviors such as learning, memory, and social interactions. Human cohort studies reveal correlations between maternal/fetal exposure to endocrine disruptors and incidence of neurodevelopmental disorders. Here, we summarize the major literature findings of endocrine disruption of neurodevelopment and concomitant changes in behavior by four major endocrine disruptor classes:bisphenol A, polychlorinated biphenyls, organophosphates, and polybrominated diphenyl ethers. We specifically review studies of gestational and/or lactational exposure to understand the effects of early life exposure to these compounds and summarize animal studies that help explain human correlative data.


Assuntos
Comportamento/efeitos dos fármacos , Disruptores Endócrinos/efeitos adversos , Sistema Nervoso/crescimento & desenvolvimento , Efeitos Tardios da Exposição Pré-Natal/patologia , Adulto , Animais , Comportamento Animal/efeitos dos fármacos , Compostos Benzidrílicos/efeitos adversos , Feminino , Humanos , Sistema Nervoso/efeitos dos fármacos , Fenóis/efeitos adversos , Bifenil Polibromatos/efeitos adversos , Bifenilos Policlorados/efeitos adversos , Gravidez
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