bisphenols

双酚
  • 文章类型: Journal Article
    双酚广泛用于聚碳酸酯塑料和树脂涂料的生产。双酚A(BPA)被认为会引起广泛的不良影响和“低剂量毒性”。随着寻找BPA的替代物质,其他双酚衍生物,即双酚F(BPF)和双酚S(BPS)的使用已经增加。
    在当前的研究中,我们旨在评估双酚衍生物对免疫和凋亡标志物以及HepG2细胞DNA损伤的计算机预测抑制浓度50(pIC50)。此外,凋亡,BPA的遗传毒性和免疫毒性作用,比较测定了BPF和BPS。通过检测不同的caspase活性来评估双酚对细胞凋亡的影响。通过测量8-羟基-2'-脱氧鸟苷(8-OHdG)和8-氧鸟嘌呤糖基化酶(OGG1)的水平来评估双酚的遗传毒性作用。为了确定双酚衍生物的免疫毒性作用,白细胞介素4(IL-4)和白细胞介素10(IL-10)的水平,转化生长因子-β(TGF-β)和肿瘤坏死因子-α(TNF-α),已知由HepG2细胞表达,被测量。结果:计算机数据表明,低剂量下所有双酚都可能导致免疫和凋亡标志物的改变以及DNA损伤。体外数据显示,所有双酚衍生物在抑制浓度30s(IC30s)下都能影响免疫标记。此外,BPF和BPS也可能具有凋亡免疫毒性作用。
    需要进一步进行计算机和体内研究,以检查替代双酚衍生物的毒性作用。
    UNASSIGNED: Bisphenols are widely used in the production of polycarbonate plastics and resin coatings. Bisphenol A (BPA) is suggested to cause a wide range of unwanted effects and \"low dose toxicity\". With the search for alternative substances to BPA, the use of other bisphenol derivatives namely bisphenol F (BPF) and bisphenol S (BPS) has increased.
    UNASSIGNED: In the current study, we aimed to evaluate the in silico predicted inhibitory concentration 50s (pIC50s) of bisphenol derivatives on immune and apoptotic markers and DNA damage on HepG2 cells. Moreover, apoptotic, genotoxic and immunotoxic effects of BPA, BPF and BPS were determined comparatively. Effects of bisphenols on apoptosis were evaluated by detecting different caspase activities. The genotoxic effects of bisphenols were evaluated by measuring the levels of 8-hydroxy-2\'-deoxyguanosine (8-OHdG) and 8-oxoguanine glycosylase (OGG1). To determine the immunotoxic effect of bisphenol derivatives, the levels of interleukin 4 (IL-4) and interleukin 10 (IL-10), transforming growth factor beta (TGF-β) and tumor necrosis factor-alpha (TNF-α), which are known to be expressed by HepG2 cells, were measured. Results: In silico data indicate that all of the bisphenols may cause alterations in immune and apoptotic markers as well as DNA damage at low doses. İn vitro data revealed that all bisphenol derivatives could affect immune markers at inhibitory concentration 30s (IC30s). In addition, BPF and BPS may also have apoptotic immunotoxic effects.
    UNASSIGNED: Both in silico and in vivo research are needed further to examine the toxic effects of alternative bisphenol derivatives.
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  • 文章类型: Journal Article
    在女性中,暴露于内分泌干扰化学物质可能会加速卵巢储备功能的消耗,并可能与加速生殖衰老和生育能力有关。我们研究了暴露于双酚和邻苯二甲酸酯与抗苗勒管激素浓度的纵向关联。
    2002年至2006年间居住在鹿特丹的18岁或以上的孕妇有资格参加这项纵向前瞻性队列研究。我们测量了1405名妇女在怀孕三个时间点的尿双酚和邻苯二甲酸酯浓度,其中1322名妇女在产后6和/或9年接受了血清抗苗勒管激素(AMH)测量。我们进行了线性回归模型,以评估6年和9年后尿双酚和邻苯二甲酸酯代谢物与AMH的关联,和线性混合效应模型来评估与AMH随时间的相关性。根据社会人口统计学和生活方式因素对模型进行了调整。
    在我们的多变量线性回归模型中,我们观察到高尿妊娠平均邻苯二甲酸单异丁酯(mIBP)的关联,单-(2-乙基-5-氧代己基)邻苯二甲酸酯(mEOHP),和邻苯二甲酸单苄基酯(mBzBP)在6年和9年后均具有较低的血清AMH。然而,在对多项测试进行校正后,这些关联并未保留.在我们的研究样本中不存在双酚A与AMH的显著关联。在我们的线性混合效应模型中,更高的mIBP,邻苯二甲酸单(2-乙基-5-羟基己基)酯(mEHHP),mEOHP,mBzBP与较低的总体AMH水平相关(差异-0.07(95%CI-0.13,-0.02),-0.09(-0.15,-0.02),-0.08(95%CI-0.14,-0.02),mIBP每倍增-0.08(-0.13,-0.03)μg/L,mEHHP,mEOHP,和mBzBP分别)(所有错误发现率调整后的p值<0.05)。
    我们发现卵巢储备指数的下降与产前邻苯二甲酸盐暴露的关系。需要研究在大型多种族非怀孕人群中复制我们的结果,并评估暴露对卵巢储备的跨代影响。
    这项研究得到了伊拉斯谟医学中心和鹿特丹伊拉斯谟大学的支持,荷兰卫生研究与发展组织,欧洲研究理事会,荷兰心脏基金会,荷兰糖尿病基金会,欧盟地平线2020研究与创新计划,美国国立卫生研究院,安什实验室韦伯斯特,和荷兰皇家艺术与科学学院。
    UNASSIGNED: In women, exposure to endocrine disrupting chemicals might accelerate the depletion of the ovarian reserve and might be associated with accelerative reproductive aging and fertility. We examined the longitudinal associations of exposure to bisphenols and phthalates with anti-Müllerian hormone concentrations.
    UNASSIGNED: Pregnant women of 18 years or older that resided in Rotterdam between 2002 and 2006 were eligible for participation in this longitudinal prospective cohort study. We measured urinary bisphenol and phthalate concentration at three time-points in pregnancy among 1405 women, of whom 1322 women had serum Anti-Müllerian Hormone (AMH) measurements 6 and/or 9 years postpartum. We performed linear regression models to assess the association of urinary bisphenol and phthalate metabolites with AMH after 6 and 9 years, and linear mixed-effect model to assess the association with AMH over time. Models were adjusted for sociodemographic and lifestyle factors.
    UNASSIGNED: In our multivariable linear regression models we observed associations of higher urinary pregnancy-averaged mono-isobutyl phthalate (mIBP), mono-(2-ethyl-5-oxohexyl) phthalate (mEOHP), and monobenzyl phthalate (mBzBP) with lower serum AMH after both 6 and 9 years. However, these associations did not remain after adjustment for multiple testing. No significant associations of bisphenol A with AMH were present in our study sample. In our linear mixed-effects models, higher mIBP, mono-(2-ethyl-5-hydroxyhexyl) phthalate (mEHHP), mEOHP, and mBzBP were associated with lower overall AMH levels (differences -0.07 (95% CI -0.13, -0.02), -0.09 (-0.15, -0.02), -0.08 (95% CI -0.14, -0.02), and -0.08 (-0.13, -0.03) μg/L per doubling in mIBP, mEHHP, mEOHP, and mBzBP respectively) (all False Discovery Rate adjusted p-values < 0.05).
    UNASSIGNED: We identify decreases in indices of ovarian reserve in relationship to prenatal phthalate exposures. Studies are needed replicating our results among large multi-ethnic non-pregnant populations and assessing transgenerational effects of exposure on ovarian reserve.
    UNASSIGNED: This study was supported by the Erasmus Medical Center and Erasmus University Rotterdam, the Netherlands Organisation for Health Research and Development, the European Research Council, the Dutch Heart Foundation, the Dutch Diabetes Foundation, the European Union\'s Horizon 2020 Research and Innovation Program, the National Institutes of Health, Ansh Labs Webster, and the Royal Netherlands Academy of Arts and Sciences.
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  • 文章类型: Journal Article
    双酚,对羟基苯甲酸酯,和三氯生(TCS)是各种消费品中使用的常见内分泌干扰物。已显示这些化学物质穿过胎盘屏障并影响胎儿的宫内发育。在这项研究中,我们量化了六种双酚的血清水平,五个对羟基苯甲酸酯,来自中国南方的483名孕妇和TCS。基于分位数的g计算表明,联合暴露于双酚,对羟基苯甲酸酯,TCS与出生体重呈显著负相关(P<0.05)(β=-39.9,95%CI:-73.8,-6.1),出生身长(β=-0.19,95%CI:-0.34,-0.04),头围(β=-0.13,95%CI:-0.24,-0.02),胸围(β=-0.16,95%CI:-0.29,-0.04)。混合物暴露与胎龄之间也存在负相关(β=-0.12,95%CI:-0.24,-0.01)。双酚A(BPA),双酚Z(BPZ),双酚AP(BPAP),对羟基苯甲酸丙酯(PrP),TCS是整体效应的主要贡献者。在亚组分析中,男性新生儿比女性更容易接触混合物,而在妊娠早期和中期的孕妇中,暴露与结局的联系显著.更多的证据是必要的,以阐明暴露于混合物对出生结果的影响,以及潜在的机制。
    Bisphenols, parabens, and triclosan (TCS) are common endocrine disrupters used in various consumer products. These chemicals have been shown to cross the placental barrier and affect intrauterine development of fetuses. In this study, we quantified serum levels of six bisphenols, five parabens, and TCS in 483 pregnant women from southern China. Quantile-based g-computation showed that combined exposure to bisphenols, parabens, and TCS was significantly (p < 0.05) and negatively associated with birth weight (β = -39.9, 95% CI: -73.8, -6.1), birth length (β = -0.19, 95% CI: -0.34, -0.04), head circumference (β = -0.13, 95% CI: -0.24, -0.02), and thoracic circumference (β = -0.16, 95% CI: -0.29, -0.04). An inverse correlation was also identified between mixture exposure and gestational age (β = -0.12, 95% CI: -0.24, -0.01). Bisphenol A (BPA), bisphenol Z (BPZ), bisphenol AP (BPAP), propylparaben (PrP), and TCS served as the dominant contributors to the overall effect. In subgroup analyses, male newborns were more susceptible to mixture exposure than females, whereas the exposure-outcome link was prominent among pregnant women in the first and second trimesters. More evidence is warranted to elucidate the impacts of exposure to mixtures on birth outcomes, as well as the underlying mechanisms.
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  • 文章类型: Journal Article
    背景:需要采取干预措施来帮助人们减少日常产品和生活习惯中有害化学物质的暴露。个人暴露的报告是提高环境健康素养(EHL)和减少暴露的准备的潜在途径。
    目的:我们的目的是确定内分泌干扰化学物质(EDC)的报告是否可以减少EDC暴露。增加EHL,并增加改变的准备程度(即,实施EDC降低暴露行为)。
    方法:健康内华达州项目的参与者在报告干预之前(n=424)和之后(n=174)完成了EHL和准备更改调查。参与者使用邮寄试剂盒来测量EDC的尿液生物标志物。结果的报告包括尿液水平,关于健康影响的信息,暴露源,和个性化的建议,以减少曝光。
    结果:基线时EHL通常非常高,特别是与一般污染有关的问题。对于与化学暴露有关的问题,在几个人口统计数据中,反应各不相同。在报告后,可以看到EHL反应的统计上可靠的改善。为了准备改变,72%的人已经或计划改变他们的行为。干预后,女性增加了他们的准备(p=0.053),而男性则减少(p=0.007)。当被问及他们在减少暴露方面面临哪些挑战时,79%的人说不知道该做什么。报告后下降到35%。对羟基苯甲酸丙酯含量较高的参与者较年轻(p=0.03),女性和健康状况良好的参与者的邻苯二甲酸酯含量较高(分别为p=0.02-0.003和p=0.001-0.003)。在报告后,在干预前后接受有效尿检的48名参与者中,邻苯二甲酸单丁酯下降(p<0.001).
    结论:报告干预是成功的,EHL行为增加证明,妇女更愿意改变,和邻苯二甲酸单丁酯的减少。对化学暴露更敏感的EHL问卷将有助于区分高识字率和低识字率。未来的研究将集中在理解为什么男性降低了改变的准备程度,以及如何改善所有参与者的干预措施。
    BACKGROUND: Interventions are needed to help people reduce exposure to harmful chemicals from everyday products and lifestyle habits. Report-back of individual exposures is a potential pathway to increasing environmental health literacy (EHL) and readiness to reduce exposures.
    OBJECTIVE: Our objective was to determine if report-back of endocrine-disrupting chemicals (EDCs) can reduce EDC exposure, increase EHL, and increase readiness to change (i.e., to implement EDC exposure-reduction behaviors).
    METHODS: Participants in the Healthy Nevada Project completed EHL and readiness-to-change surveys before (n = 424) and after (n = 174) a report-back intervention. Participants used mail-in kits to measure urinary biomarkers of EDCs. The report-back of results included urinary levels, information about health effects, sources of exposure, and personalized recommendations to reduce exposure.
    RESULTS: EHL was generally very high at baseline, especially for questions related to the general pollution. For questions related to chemical exposures, responses varied across several demographics. Statistically reliable improvements in EHL responses were seen after report-back. For readiness to change, 72% were already or planning to change their behaviors. Post-intervention, women increased their readiness (p = 0.053), while men decreased (p = 0.007). When asked what challenges they faced in reducing exposure, 79% cited not knowing what to do. This dropped to 35% after report-back. Participants with higher propylparaben were younger (p = 0.03) and women and participants who rated themselves in better health had higher levels of some phthalates (p = 0.02-0.003 and p = 0.001-0.003, respectively). After report-back, monobutyl phthalate decreased among the 48 participants who had valid urine tests before and after the intervention (p < 0.001).
    CONCLUSIONS: The report-back intervention was successful as evidenced by increased EHL behaviors, increased readiness to change among women, and a decrease in monobutyl phthalate. An EHL questionnaire more sensitive to chemical exposures would help differentiate high and low literacy. Future research will focus on understanding why men decreased their readiness to change and how the intervention can be improved for all participants.
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  • 文章类型: Journal Article
    类固醇激素失衡被认为会增加发展PE的几率。双酚A(BPA)及其替代品(例如,双酚S(BPS)和双酚F(BPF)具有类似雌激素的作用,其暴露可能与先兆子痫(PE)的发生有关。探讨双酚暴露对母体血清类固醇激素的影响以及类固醇激素在双酚暴露与发展中PE之间的潜在中介作用。在分娩前检查383例孕妇血清中的双酚和类固醇激素浓度(包括160例PE和223例对照病例)。使用多变量逻辑和线性模型来探索母体血清双酚浓度与母体类固醇激素和PE风险的关系。采用中介模型来评估类固醇激素在双酚和PE之间的关联中的中介作用。结果显示,母体血清BPS浓度与睾酮(T)浓度呈正相关。调解分析表明,大约10.17%的BPS浓度和PE的发展之间的关联可能是由母体T介导的。孕妇在怀孕期间暴露于BPS与更高的孕妇T浓度有关,这可能会增加发展体育的几率。T可能介导BPS暴露与PE发展之间的关联。
    Steroid hormone imbalance is believed to increase the odds of developing PE. Bisphenol A (BPA) and its substitutes (e.g., bisphenol S (BPS) and bisphenol F (BPF)) have estrogen-like effects, and its exposure may be related to the development of preeclampsia (PE). To explore the effects of bisphenol exposure on maternal serum steroid hormones and the potential mediating role of steroid hormones in the association between bisphenol exposure and developing PE, concentrations of bisphenols and steroid hormones in serum samples of 383 pregnant women were examined before delivery (including 160 PE cases and 223 control cases). Multivariable logistic and linear models were used to explore the associations of maternal serum bisphenols concentrations with both maternal steroid hormones and PE risk. Mediation modeling was employed to evaluate the mediating role of steroid hormones in the association between bisphenols and PE. Results showed that maternal serum BPS concentrations were positively associated with testosterone (T) concentrations. The mediation analyses suggested that approximately 10.17 % of the associations between BPS concentrations and the development of PE might be mediated by maternal T. In conclusion, maternal exposure to BPS during pregnancy is linked to higher maternal T concentrations, which might increase the odds of developing PE. T might mediate the association between BPS exposure and the development of PE.
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  • 文章类型: Journal Article
    轮胎磨损颗粒(TWP)被认为是海洋环境中微塑料污染的重要组成部分,并与各种水生污染物一起出现,包括经常检测到的双酚。TWP或双酚对水生生物的不利影响已被广泛报道。然而,TWP和双酚的联合毒性仍然未知。在这项研究中,原始(p-)和老化的TWPs(a-TWPs)和四种双酚((双酚A(BPA),双酚F(BPF),双酚S(BPS),和双酚AF(BPAF))对日本虎杖进行了评估。TWPs增加了BPA和BPF的毒性,但降低了BPAF的毒性。对于BPS,在p-TWP的存在下存在协同毒性作用,但在a-TWP存在下观察到轻微的拮抗作用。TWP对BPAF的吸附导致其对co足类的毒性降低。A-TWPs比p-TWPs释放更多的锌,释放的Zn有助于TWPs和BPA或BPF的协同作用。由特定大小的TWP形成的聚集(例如,90-110μm)可引起日本竹节虫的肠道损伤和脂质过氧化。p-TWP和BPS的协同作用可能是由于二元混合物的聚集大小。当前研究的结果对于理解TWPs和双酚的联合毒性作用以及二元混合物的潜在毒性机制将是重要的。
    Tire wear particles (TWPs) are considered an important component of microplastic pollution in the marine environment and occur together with a variety of aquatic pollutants, including frequently detected bisphenols. The adverse effects of TWPs or bisphenols on aquatic organisms have been widely reported. However, the combined toxicity of TWPs and bisphenols is still unknown. In this study, the combined toxicity of both pristine (p-) and aged TWPs (a-TWPs) and four bisphenols ((bisphenol A (BPA), bisphenol F (BPF), bisphenol S (BPS), and bisphenol AF (BPAF)) to Tigriopus japonicus was evaluated. TWPs increased the toxicity of BPA and BPF but decreased the toxicity of BPAF. For BPS, there was synergistic toxic effect in the presence of p-TWPs, but slightly antagonistic effect was observed in the presence of a-TWPs. This adsorption of BPAF by TWPs resulted in a reduction of its toxicity to the copepod. A-TWPs could release more Zn than p-TWPs, and the released Zn contributed to the synergistic effect of TWPs and BPA or BPF. The aggregation formed by TWPs in certain sizes (e.g., 90-110 μm) could cause intestinal damage and lipid peroxidation in T. japonicus. The synergistic effect of p-TWPs and BPS might be due to the aggregation size of the binary mixture. The results of the current study will be important to understand the combined toxic effect of TWPs and bisphenols and the potential toxic mechanisms of the binary mixture.
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  • 文章类型: Journal Article
    双酚威胁人类健康,敏感检测至关重要。本研究旨在开发具有AuAg微结构的铜金属有机骨架(Cu-MOF)三元复合材料。复合结构是通过电流置换反应形成的,并使用SEM进行了确认。使用无粘合剂催化剂研究双酚A(BPA)和双酚S(BPS)的电化学氧化还原反应;在0.70V和0.91V下的不可逆循环伏安信号(vs.Ag/AgCl),在20nM至2.0mM的动态范围内,和10nM至1.0mM,检出限为2.9nM,并且获得3.2nM(S/N=3)。对冷冻番茄进行了实际分析,金枪鱼,奶粉,PET瓶,生牛奶,和尿液样品的回收率为94.00-100.80%(n=3)。使用HPLC检测以高精度验证伏安结果。该传感器是用于测量食品样品中BPA的有前途的替代平台。
    Bisphenols threaten human health and sensitive detection is crucial. The present study aims to develop ternary composites of copper metal-organic framework (Cu-MOF) with AuAg microstructures. The composite structure was formed by a galvanic displacement reaction and confirmed using SEM. A binder-free catalyst was used to study the electrochemical redox reaction of bisphenol A (BPA) and bisphenol S (BPS); an irreversible cyclic voltammetric signal at +0.70 V and + 0.91 V (vs. Ag/AgCl), in the dynamic range of 20 nM to 2.0 mM, and 10 nM to 1.0 mM, with limits of detection of 2.9 nM, and 3.2 nM (S/N = 3) was obtained. Practical analysis was applied to frozen tomatoes, tuna fish, milk powder, PET bottles, raw milk, and urine samples with a recovery rate of 94.00-100.80% (n = 3). Voltammetric results were validated using HPLC detection with high precision. The sensor is a promising alternative platform for measuring BPA in food samples.
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  • 文章类型: Systematic Review
    来自动物实验和流行病学研究的证据报道了关于产前双酚(BPs)暴露对儿童甲状腺功能影响的有争议的结果。本研究旨在探讨新生儿和幼儿产前暴露于BPs与甲状腺相关激素(THs)的关系。特别关注性别依赖和暴露水平的影响。
    相关研究从PubMed进行了系统搜索,WebofScience,Medline,科克伦,和Embase直到2024年2月21日。评估的暴露量包括双酚A(BPA),双酚F(BPF),双酚S(BPS),双酚AF(BPAF),和四氯双酚A(TCBPA)。测量的THs是促甲状腺激素(TSH),总三碘甲状腺原氨酸(TT3),总甲状腺素(TT4),游离三代甲状腺素(FT3),和游离甲状腺素(FT4)。使用多变量回归模型的系数量化效果估计值。使用Stata16.0完成统计分析。采用纽卡斯尔-渥太华量表(NOS)评价纳入研究的方法学质量。
    11项队列研究包括5363名儿童纳入我们的荟萃分析。产前双酚浓度与儿童甲状腺激素变化有统计学意义,只在雌性后代中,包括TSH降低(β=-0.020,95%CI:-0.036,-0.005)和TT3水平升高(β=0.011,95%CI:0.001,0.021),和暴露于高浓度的双酚(>1.5ug/g肌酐)显着降低了儿童的FT3水平(β=-0.011,95%CI:-0.020,-0.003)。
    产前双酚暴露与女孩甲状腺激素水平的改变有关,有必要加强措施以控制怀孕期间的双酚暴露水平,以保护儿童健康。
    https://inplasy.com,标识符INPLASY202450129。
    UNASSIGNED: Evidence from animal experiments and epidemiological studies has reported controversial results about the effects of prenatal bisphenols (BPs) exposure on childhood thyroid function. This study aims to explore the associations of prenatal exposure to BPs with thyroid-related hormones (THs) in newborns and early childhood, with a particular focus on the sex-dependent and exposure level effects.
    UNASSIGNED: Correlated studies were systematically searched from PubMed, Web of Science, Medline, Cochrane, and Embase until February 21, 2024. The exposures assessed include bisphenol A (BPA), bisphenol F (BPF), bisphenol S (BPS), bisphenol AF (BPAF), and tetrachlorobisphenol A (TCBPA). THs measured were thyroid stimulating hormone (TSH), total tri-iodothyronine (TT3), total thyroxine (TT4), free tri-iothyronine (FT3), and free thyroxine (FT4). Effect estimates were quantified using coefficients from multivariable regression models. Statistical analyses were completed using Stata 16.0. The methodological quality of the included studies was evaluated using the Newcastle-Ottawa Scale (NOS).
    UNASSIGNED: Eleven cohort studies comprising 5,363 children were included in our meta-analysis. Prenatal bisphenol concentrations were statistically significant related to alterations in thyroid hormones in children, exclusively in female offspring, including reduced TSH (β = -0.020, 95% CI: -0.036, -0.005) and increased TT3 levels (β = 0.011, 95% CI: 0.001, 0.021), and exposure to high concentration of bisphenols (>1.5 ug/g creatinine) significantly reduced FT3 levels in children (β = -0.011, 95% CI: -0.020, -0.003).
    UNASSIGNED: Prenatal bisphenol exposure is linked to alterations in thyroid hormone levels in girls, necessitating enhanced measures to control bisphenol exposure levels during pregnancy for child health protection.
    UNASSIGNED: https://inplasy.com, identifier INPLASY202450129.
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  • 文章类型: Journal Article
    已知内分泌干扰化学物质(EDC)会干扰内分泌稳态。它们对肾上腺皮质和类固醇生成的影响尚未得到充分阐明。这特别适用于普遍存在的双酚A(BPA),F(BPF),S(BPS)。
    NCI-H295R肾上腺皮质细胞暴露于不同浓度(1nM-1mM)的BPA,BPF,BPS,和它们的等摩尔混合物(BPmix)。72小时后,使用LC-MS/MS测量了15种内源性类固醇。计算CYP调节步骤的底物和产物的比率,以鉴定受影响最大的类固醇生成步骤。通过实时PCR确定类固醇生成酶的mRNA表达。
    双酚浓度低于250µM时,细胞活力不受影响。所有测试的双酚及其组合导致定量类固醇水平的广泛改变。雄烯二酮暴露于BPA(>10µM)后,类固醇浓度的最大倍数变化(FC)。例如,与媒介物处理的对照相比,在25µM(p≤0.0001)时下降了0.37±0.11倍。对于BPF,17-羟孕酮的水平显著增加了25µM(FC2.57±0.49,p≤0.001)和50µM(FC2.65±0.61,p≤0.0001).BPS治疗导致11-脱氧皮质酮在>1µM时的剂量依赖性下降(例如FC0.24±0.14,在10µM时p≤0.0001)。然而,当结合所有三种双酚时,加性效应被检测到:例如,11-脱氧皮质酮在剂量>10µM时降低(FC0.27±0.04,p≤0.0001,在25µM时),而21-脱氧皮质醇在10µM时增加了2.92±0.20(p≤0.01),在50µM下为3.21±0.45(p≤0.001)。虽然每个测量的雄激素(DHEA,DHEAS,雄烯二酮,睾丸激素,DHT)在所有实验中都降低了,雌二醇水平显着增加BPA,BPF,BPS,和BPmix(例如FC3.60±0.54,在100µMBPF时p≤0.0001)。计算的底物-产物比率表明CYP17A1-的抑制作用,和CYP21A2介导的转化,而CYP11B1和CYP19A1在双酚存在下显示出更高的活性。基于这些发现,分析了CYP基因最相关的mRNA表达。StAR的mRNA水平,CYP11B1和CYP17A1被BPF显著增高,BPS,还有BPmix.
    在细胞培养中,双酚在非细胞毒性水平上干扰类固醇生成,导致激素水平显著改变的化合物特异性模式。这些结果证明并要求进行其他体内研究以评估EDC对肾上腺功能的影响。
    UNASSIGNED: Endocrine disrupting chemicals (EDCs) are known to interfere with endocrine homeostasis. Their impact on the adrenal cortex and steroidogenesis has not yet been sufficiently elucidated. This applies in particular to the ubiquitously available bisphenols A (BPA), F (BPF), and S (BPS).
    UNASSIGNED: NCI-H295R adrenocortical cells were exposed to different concentrations (1nM-1mM) of BPA, BPF, BPS, and an equimolar mixture of them (BPmix). After 72 hours, 15 endogenous steroids were measured using LC-MS/MS. Ratios of substrate and product of CYP-regulated steps were calculated to identify most influenced steps of steroidogenesis. mRNA expression of steroidogenic enzymes was determined by real-time PCR.
    UNASSIGNED: Cell viability remained unaffected at bisphenol concentrations lower than 250 µM. All tested bisphenols and their combination led to extensive alterations in the quantified steroid levels. The most profound fold changes (FC) in steroid concentrations after exposure to BPA (>10µM) were seen for androstenedione, e.g. a 0.37±0.11-fold decrease at 25µM (p≤0.0001) compared to vehicle-treated controls. For BPF, levels of 17-hydroxyprogesterone were significantly increased by 25µM (FC 2.57±0.49, p≤0.001) and 50µM (FC 2.65±0.61, p≤0.0001). BPS treatment led to a dose-dependent decrease of 11-deoxycorticosterone at >1µM (e.g. FC 0.24±0.14, p≤0.0001 at 10µM). However, when combining all three bisphenols, additive effects were detected: e.g. 11-deoxycortisosterone was decreased at doses >10µM (FC 0.27±0.04, p≤0.0001, at 25µM), whereas 21-deoxycortisol was increased by 2.92±0.20 (p≤0.01) at 10µM, and by 3.21±0.45 (p≤0.001) at 50µM. While every measured androgen (DHEA, DHEAS, androstenedione, testosterone, DHT) was lowered in all experiments, estradiol levels were significantly increased by BPA, BPF, BPS, and BPmix (e.g. FC 3.60±0.54, p≤0.0001 at 100µM BPF). Calculated substrate-product ratios indicated an inhibition of CYP17A1-, and CYP21A2 mediated conversions, whereas CYP11B1 and CYP19A1 showed higher activity in the presence of bisphenols. Based on these findings, most relevant mRNA expression of CYP genes were analysed. mRNA levels of StAR, CYP11B1, and CYP17A1 were significantly increased by BPF, BPS, and BPmix.
    UNASSIGNED: In cell culture, bisphenols interfere with steroidogenesis at non-cytotoxic levels, leading to compound-specific patterns of significantly altered hormone levels. These results justify and call for additional in-vivo studies to evaluate effects of EDCs on adrenal gland functionality.
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  • 文章类型: Journal Article
    聚合物整料可以在不同的模具内聚合,但有限的选择可用于制备分析样品的独立聚合物整料,特别是,固相萃取(SPE)。商业三聚氰胺-甲醛海绵可用作制备聚合物整料的载体,由于其灵活性,赋予巨石各种形状。在这里,已经评估了高度多孔海绵嵌套的二乙烯基苯(DVB)聚合物整料的交联剂/致孔剂比率。使用不同的交联剂/致孔剂比例制备的整料应用于双酚F的提取,双酚A,双酚AF,含有50重量%DVB和50重量%致孔剂的整料呈现最高的双酚回收率。在优化条件下,所开发的方法显示BPA和BPAF的线性范围在2.5µgL-1和150µgL-1之间,BPB和BPF在5µgL-1和150µgL-1之间。检测限(LOD,S/N=3)和定量限(LOQ,S/N=10)的范围分别为0.36µgL-1至1.09µgL-1和1.20µgL-1至3.65µgL-1。在自来水和聚碳酸酯容器中的水中,掺加的双酚(10µgL-1)的回收率在82%至114%之间。
    Polymer monoliths can be polymerised within different molds, but limited options are available for the preparation of free-standing polymer monoliths for analytical sample preparation, and in particular, solid-phase extraction (SPE). Commercial melamine-formaldehyde sponges can be used as supports for the preparation of polymer monoliths, due its flexibility, giving various shapes to monoliths. Herein, the crosslinker/porogen ratio of highly porous sponge-nested divinylbenzene (DVB) polymer monoliths has been evaluated. Monoliths prepared using different crosslinker/porogen ratios were applied to the extraction of bisphenol F, bisphenol A, bisphenol AF, and bisphenol B. Monoliths containing 50 wt % DVB and 50 wt % porogens presented the highest recovery of bisphenols. Under the optimised conditions, the developed method showed a linear range between 2.5 µg L-1 and 150 µg L-1 for BPA and BPAF, and between 5 µg L-1 and 150 µg L-1 for BPB and BPF. The limits of detection (LOD, S/N = 3) and limits of quantification (LOQ, S/N = 10) ranged from 0.36 µg L-1 to 1.09 µg L-1, and from 1.20 µg L-1 to 3.65 µg L-1, respectively. The recoveries for spiked bisphenols (10 µg L-1) in tap water and water contained in a polycarbonate containers were between 82 % and 114 %.
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