Toxicology in Vitro最新文献_第5页

Effects of heated tobacco products and conventional cigarettes on oxidative stress and inflammation in alveolar macrophages 加热烟草制品和传统香烟对肺泡巨噬细胞氧化应激和炎症的影响。

IF 2.7 3区医学 Q3 TOXICOLOGY

Toxicology in Vitro

Pub Date : 2025-09-26 DOI: 10.1016/j.tiv.2025.106151

Ok Joo Sul , Hye Won Choi , Seo Hee Park , Min Ju Kim , Seung Won Ra

Oxidative stress in macrophages is a major factor contributing to smoking-induced chronic respiratory diseases. However, the oxidative stress induced by heat-not-burn tobacco products (HTP) and conventional cigarettes (3R4F) in macrophages has not been sufficiently investigated. This study compared the effects of HTP and 3R4F cigarettes on cytotoxicity and oxidative stress. We also investigated the underlying mechanisms of autophagy-induced inflammation in macrophages. Our results showed that both HTP and 3R4F cigarette aerosols induced cytotoxicity; however, HTP aerosol was less cytotoxic than conventional cigarette aerosol in RAW264.7 cells. In addition, both aerosols resulted in increased reactive oxygen species (ROS) levels in RAW 264.7 and bone marrow-derived macrophages (BMMs), although the levels were lower for HTP aerosol than for 3R4F aerosol. Additionally, acute exposure to HTP aerosol elevated the levels of IL-1β, IL-6, and TNF-α in macrophages. Oxidative stress-triggered TFEB oxidation induced TFEB nuclear translocation, thereby enhancing autophagy and inflammation in HTP- and 3R4F-exposed macrophages. In conclusion, our study demonstrated that aerosols from HTP and 3R4F cigarettes increased the cytotoxicity in macrophages. Cigarette aerosols increase oxidative stress, which triggers TFEB oxidation and increases its nuclear translocation. TFEB oxidation leads to increased autophagy and inflammation in HTP- or 3R4F aerosol-exposed macrophages. Exposure to HTP aerosols resulted in lower cytotoxicity, oxidative stress, and inflammatory responses than the exposure to conventional cigarettes in vitro.

巨噬细胞的氧化应激是导致吸烟引起的慢性呼吸系统疾病的一个主要因素。然而，热不燃烟草制品（HTP）和传统香烟（3R4F）在巨噬细胞中诱导的氧化应激尚未得到充分的研究。本研究比较了HTP和3R4F香烟对细胞毒性和氧化应激的影响。我们还研究了巨噬细胞自噬诱导炎症的潜在机制。结果表明，HTP和3R4F卷烟气溶胶均诱导细胞毒性；然而，HTP气雾剂对RAW264.7细胞的细胞毒性低于传统香烟气雾剂。此外，两种气溶胶均导致RAW 264.7和骨髓源性巨噬细胞（BMMs）中的活性氧（ROS）水平升高，尽管HTP气溶胶的水平低于3R4F气溶胶。此外，急性暴露于HTP气溶胶会升高巨噬细胞中IL-1β、IL-6和TNF-α的水平。氧化应激触发的TFEB氧化诱导TFEB核易位，从而增强HTP-和3r4f暴露的巨噬细胞的自噬和炎症。总之，我们的研究表明，HTP和3R4F香烟的气溶胶增加了巨噬细胞的细胞毒性。香烟气溶胶增加氧化应激，从而触发TFEB氧化并增加其核易位。TFEB氧化导致HTP-或3R4F气溶胶暴露的巨噬细胞自噬和炎症增加。在体外实验中，与传统香烟相比，暴露于HTP气溶胶导致的细胞毒性、氧化应激和炎症反应更低。

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引用次数: 0

Tributyltin propionate and tributyltin salicylate represent novel RXR ligands: Effects on transcriptional activity of thyroid hormone receptor and vitamin D3 receptor 丙酸三丁基锡和水杨酸三丁基锡为新型RXR配体：对甲状腺激素受体和维生素D3受体转录活性的影响

IF 2.7 3区医学 Q3 TOXICOLOGY

Toxicology in Vitro

Pub Date : 2025-09-25 DOI: 10.1016/j.tiv.2025.106153

Dana Macejova , Jakub Kollar , Zdenek Dvorak , Daniela Schuster , Julius Brtko

Several organometallic trialkyltins or triaryltins are known to act as retinoid X receptor (RXR) agonists, which were also reported to exert eminent cytotoxic properties. In the present study, binding properties of tributyltin propionate (TBT-P) and tributyltin salicylate (TBT-S) in RXRα molecule were theoretically investigated using docking in Schrödinger small molecule drug discovery suite. Our data has shown that TBT-P and TBT-S bind in the binding pocket of RXRα and represent novel RXR agonists. In vitro data has shown that both TBT-P and TBT-S exert transcriptional activity under basal and ligand-activated conditions through RXR − nuclear thyroid hormone receptor (TR) heterodimer in the human reporter cell line for the assessment of thyroid receptor transcriptional activity (PZ-TR). In the human reporter cell line, enabling sensitive and selective identification of nuclear dihydroxyvitamin D₃ receptor (VDR) agonists (IZ-VDRE), TBT-P and TBT-S did not exert any transcriptional activity through VDR under basal and ligand-activated conditions, which is in agreement with the properties of the non-permissive type of RXR-VDR heterodimer. Our in silico and in vitro data demonstrate that both organometallic compounds TBT-P and TBT-S represent new nuclear retinoid X receptor agonists.

已知几种有机金属三烷基丁素或三芳丁素可作为类视黄醇X受体（RXR）激动剂，也有报道称其具有显著的细胞毒性。本研究通过对接Schrödinger小分子药物发现套件，从理论上研究了丙酸三丁基锡（TBT-P）和水杨酸三丁基锡（TBT-S）在RXRα分子上的结合特性。我们的数据表明，TBT-P和TBT-S结合在RXRα的结合口袋中，代表了新型的RXR激动剂。体外实验表明，TBT-P和TBT-S在基础和配体激活条件下均通过RXR -核甲状腺激素受体（TR）异源二聚体在人报告细胞系中发挥转录活性，用于评估甲状腺受体转录活性（PZ-TR）。在人类报告细胞系中，能够敏感和选择性地鉴定核二羟维生素D3受体（VDR）激动剂（IZ-VDRE）， TBT-P和TBT-S在基础和配体激活条件下没有通过VDR发挥任何转录活性，这与非允许型RXR-VDR异源二聚体的性质一致。我们的硅和体外数据表明，有机金属化合物TBT-P和TBT-S都是新的核类视黄醇X受体激动剂。

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引用次数: 0

The pesticide fungicide difenoconazole modulates the biophysical properties of sodium channel Nav1.5 农药杀菌剂异苯唑调节钠通道Nav1.5的生物物理性质。

IF 2.7 3区医学 Q3 TOXICOLOGY

Toxicology in Vitro

Pub Date : 2025-09-24 DOI: 10.1016/j.tiv.2025.106152

V. Fogaça-Santos , F.S. Alcântara , M.R.L. Conceição , L.P. Marques , J.L. Teixeira-Fonseca , D.J.B. Orts , J. Branquinho , R.L. Morais , K.O. Mota , D.S. Souza , J.B. Pesquero , D. Roman-Campos

Difenoconazole (DIF) is a widely used fungicide in agriculture, but it is unknown if it can modulate the excitability of the heart tissue. Thus, we investigated the acute effect of DIF on the electrical properties of heart tissue, with a particular focus on the cardiac sodium channel (Na_v1.5) using transient expression of human Na_v1.5 in human kidney cell (HEK) and human cardiomyocytes derived from induced pluripotent stem cells (CM-hiPSCs). DIF reduced the peak amplitude of sodium current (I_Na) in a concentration dependent manner. While DIF did not alter the voltage dependence of activation, it shifted the I_Na inactivation curve to more negative potentials and delayed the recovery from inactivation. In silico simulation identified aminoacids Thr1710 and Val1765 as critical for the interaction between DIF with Na_v1.5. DIF partially blocked the late sodium current induced by deltamethrin, a pyrethroid pesticide, suggesting a potential interaction between these compounds in the environment. In CM-hiPSCs, DIF completely abolished the action potential. These findings suggest that DIF may modulate the biophysical properties of Na_v1.5 and modulate cellular excitability which may cause reduced heart excitability, an DIF can also counteracting the effects of pyrethroid pesticides, but further studies using DIF concentrations closer to human exposure levels are necessary.

二苯醚康唑（DIF）是一种广泛应用于农业的杀菌剂，但它是否能调节心脏组织的兴奋性尚不清楚。因此，我们研究了DIF对心脏组织电学特性的急性影响，特别关注了钠通道（Nav1.5），通过在人肾细胞（HEK）和诱导多能干细胞（CM-hiPSCs）衍生的人心肌细胞中瞬时表达人Nav1.5。DIF以浓度依赖性的方式降低了钠电流（INa）的峰值幅度。虽然DIF没有改变激活的电压依赖性，但它使INa失活曲线向更多的负电位移动，并延迟了从失活恢复的时间。硅模拟鉴定出氨基酸Thr1710和Val1765对DIF与Nav1.5之间的相互作用至关重要。DIF部分阻断了溴氰菊酯（一种拟除虫菊酯类杀虫剂）诱导的后期钠电流，表明这些化合物在环境中可能存在相互作用。在CM-hiPSCs中，DIF完全消除了动作电位。这些发现表明，DIF可能调节Nav1.5的生物物理特性，并调节细胞兴奋性，从而可能导致心脏兴奋性降低，并且DIF还可以抵消拟除虫菊酯杀虫剂的影响，但需要使用更接近人类暴露水平的DIF浓度进行进一步研究。

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引用次数: 0

First toxicity profile of aminoindane-based new psychoactive substances: 2-aminoindane (2-AI, CAS: 2975-41-9) and N-Methyl-2-aminoindane (NM-2-AI, CAS: 24445–44–1) – comprehensive prediction of toxicological endpoints important from clinical and forensic perspective using in silico multi- approach 基于氨基吲哚胺的新型精神活性物质：2-氨基吲哚胺（2-AI, CAS: 2975-41-9）和n -甲基-2-氨基吲哚胺（NM-2-AI, CAS: 24445-44-1）的第一个毒性谱-从临床和法医角度使用硅多方法综合预测毒理学终点很重要。

IF 2.7 3区医学 Q3 TOXICOLOGY

Toxicology in Vitro

Pub Date : 2025-09-24 DOI: 10.1016/j.tiv.2025.106149

Kamil Jurowski , Adrian Frydrych

This study provides the first toxicity profile of two aminoindane-based new psychoactive substances (NPS): 2-aminoindane (2-AI) and N-methyl-2-aminoindane (NM-2-AI), using a multi-method in silico approach. Tools including Percepta, ProTox 3.0, ADMETlab 3.0, VEGA QSAR, TEST, QSAR Toolbox, and STopTox were applied to evaluate acute toxicity, systemic organ effects, genotoxicity, skin and eye irritation, and cardiotoxicity. Both compounds were predicted to be acutely toxic via oral, dermal, and inhalation routes. Quantitative LD₅₀ values (rat, oral) ranged from 150 to 560 mg/kg (Percepta), 259.7–112.6 mg/kg (VEGA), and 326–360 mg/kg (ProTox 3.0). Health effect predictions indicated high probabilities of cardiovascular toxicity (2-AI: 80 %, NM-2-AI: 82 %) and pulmonary involvement (66 % and 65 %, respectively). NM-2-AI showed a higher likelihood of genotoxicity (Ames test) with a probability of 66.3 % (ADMETlab), compared to 2-AI (58.7 %). Both substances were predicted to be non-irritant to the eye, but skin irritation was probable for 2-AI (80 %, StopTox) and less so for NM-2-AI (60 %). hERG inhibition risk was low (IC₅₀: 391.7 μM for 2-AI; 126.9 μM for NM-2-AI). The in silico multi-tool strategy yielded convergent and interpretable data, supporting early toxicological characterization. These results are relevant for clinical management of NPS intoxications and for forensic interpretation in the absence of experimental data.

本研究采用多方法对2-氨基indine （2-AI）和n -甲基-2-氨基indine （NM-2-AI）这两种基于氨基indine的新型精神活性物质（NPS）进行了首次毒性分析。应用Percepta、ProTox 3.0、ADMETlab 3.0、VEGA QSAR、TEST、QSAR工具箱和STopTox等工具评估急性毒性、全身器官效应、遗传毒性、皮肤和眼睛刺激以及心脏毒性。预计这两种化合物通过口服、皮肤和吸入途径具有急性毒性。定量LD₅0值（大鼠，口服）范围为150至560 mg/kg (Percepta), 259.7-112.6 mg/kg （VEGA）和326-360 mg/kg （ProTox 3.0）。健康影响预测表明，心血管毒性（2-AI: 80 %,NM-2-AI: 82 %）和肺部损害（分别为66 %和65 %）的可能性很高。与2-AI（58.7 %）相比，NM-2-AI显示出更高的遗传毒性可能性（Ames试验），概率为66.3% % （ADMETlab）。预测这两种物质对眼睛无刺激性，但2-AI可能对皮肤有刺激性（80% %,StopTox），而NM-2-AI则较少（60% %）。hERG抑制风险低（IC₅₀：391.7 2-AI μM; NM-2-AI 126.9 μM）。计算机多工具策略产生了收敛和可解释的数据，支持早期毒理学表征。这些结果与NPS中毒的临床管理和缺乏实验数据的法医解释相关。

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引用次数: 0

Collaborative evaluation of in silico predictions for high throughput toxicokinetics 高通量毒物动力学的协同评估。

IF 2.7 3区医学 Q3 TOXICOLOGY

Toxicology in Vitro

Pub Date : 2025-09-20 DOI: 10.1016/j.tiv.2025.106150

John F. Wambaugh , Nisha S. Sipes , Gilberto Padilla Mercado , Jon A. Arnot , Linda Bertato , Trevor N. Brown , Nicola Chirico , Christopher Cook , Daniel E. Dawson , Sarah E. Davidson-Fritz , Stephen S. Ferguson , Michael-Rock Goldsmith , Chris M. Grulke , Richard S. Judson , Kamel Mansouri , Grace Patlewicz , Ester Papa , Prachi Pradeep , Alessandro Sangion , Risa R. Sayre , Michael J. Devito

High throughput toxicokinetic (HTTK) methods address chemical risk assessment data gaps but require chemical-specific values that can be obtained by in vitro measurements or in silico models. In this study, seven quantitative structure property relationship (QSPR) models were used to estimate intrinsic hepatic clearance (Cl_int), fraction of chemical unbound in plasma (f_up), and/or TK elimination half-life (t_½). Performance of the QSPR models was evaluated using literature time-course in vivo TK data, mainly from rats. Simulations of the in vivo data were made with a high throughput physiologically based TK (HT-PBTK) model using the different QSPR model predictions as inputs. We estimate that using rat in vivo data to evaluate QSPR models trained on human in vitro measured data might inflate error estimates by as much as root mean squared log₁₀ error (RMSLE) 0.8. A sensitivity analysis showed that Cl_int and f_up parameters inform predictions of area under the curve (AUC) and steady-state concentration (C_ss). We estimate that AUC can be predicted by HTTK with RMSLE 0.9 using in vitro measurements and 0.6–0.8 using QSPR model values. We anticipate that, for some novel compounds, QSPRs for HTTK input parameters will give predictions of TK similar to those based on in vitro measurements.

高通量毒物动力学（HTTK）方法解决了化学品风险评估数据缺口，但需要通过体外测量或硅模型获得化学品特定值。在这项研究中，七个定量结构性质关系（QSPR）模型被用于估计内在肝脏清除率（Clint），血浆中化学未结合物的比例（fup）和/或TK消除半衰期（t½）。QSPR模型的性能通过文献中主要来自大鼠的体内TK数据进行评估。采用高通量生理TK （HT-PBTK）模型，以不同的QSPR模型预测作为输入，对体内数据进行模拟。我们估计，使用大鼠体内数据来评估基于人类体外测量数据训练的QSPR模型可能会将误差估计夸大至均方根log10误差（RMSLE） 0.8。灵敏度分析表明，Clint和fup参数可以预测曲线下面积（AUC）和稳态浓度（Css）。我们估计，体外测量时，HTTK可以预测AUC， RMSLE为0.9，QSPR模型值为0.6-0.8。我们预计，对于一些新化合物，HTTK输入参数的qprs将给出类似于基于体外测量的TK预测。

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引用次数: 0

Synergistic and divergent effects of dietary sugars on hepatocyte viability and steatosis 膳食糖对肝细胞活力和脂肪变性的协同和发散效应。

IF 2.7 3区医学 Q3 TOXICOLOGY

Toxicology in Vitro

Pub Date : 2025-09-18 DOI: 10.1016/j.tiv.2025.106148

Ajay Kumar , Garhima Arora , Deepika Kumari , Harish Changotra , Samrat Chatterjee

Our study explores the effects of glucose, fructose, and sucrose on hepatocyte health, focusing on cell viability and lipid accumulation. Hepatocyte cells (HepG2) were exposed to a range of concentrations of glucose, fructose and sucrose, both individually and in combination, over 24, 48, and 72 h. Cell viability was monitored using the MTT assay, while lipid accumulation was estimated fluorometrically using Nile red staining. Our findings suggest that higher concentrations of fructose significantly improves cell viability in a dose-dependent manner, especially in hepatocyte cells exposed to fructose for extended duration. Additionally, a time-dependent increase in lipid accumulation was seen, particularly in cells exposed to fructose. Interestingly, enhanced hepatocyte viability was noted with combinations of glucose with fructose or sucrose, without detrimental effects. Lipid accumulation was more pronounced with glucose-fructose combinations. These results provide insights into the differential effects of dietary sugars on liver health and metabolism, with implications for understanding metabolic disorders like MASLD and MASH.

我们的研究探讨了葡萄糖、果糖和蔗糖对肝细胞健康的影响，重点是细胞活力和脂质积累。将肝细胞（HepG2）单独或联合暴露于不同浓度的葡萄糖、果糖和蔗糖中，时间分别为24、48和72 h。使用MTT法监测细胞活力，同时使用尼罗红染色法估计脂质积累。我们的研究结果表明，高浓度的果糖以剂量依赖的方式显著提高细胞活力，特别是在长时间暴露于果糖的肝细胞中。此外，脂质积累的时间依赖性增加，特别是在暴露于果糖的细胞中。有趣的是，葡萄糖与果糖或蔗糖的组合可以增强肝细胞活力，但没有有害影响。脂质积累在葡萄糖-果糖组合中更为明显。这些结果为了解膳食糖对肝脏健康和代谢的不同影响提供了见解，对理解MASLD和MASH等代谢紊乱具有重要意义。

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引用次数: 0

Binding of plutonium and americium to small molecular weight ligands favors their paracellular transfer across lung epithelium in vitro 钚和镅与小分子量配体的结合有利于其在体外肺上皮细胞旁转移。

IF 2.7 3区医学 Q3 TOXICOLOGY

Toxicology in Vitro

Pub Date : 2025-09-18 DOI: 10.1016/j.tiv.2025.106146

G. Drouet , A. Bourgois , K. Devilliers , M. Defrance , A. Van der Meeren

Pulmonary absorption is a critical step in the time-dependent processes governing actinide biodistribution and toxicity following internal contamination by inhalation. The current study was undertaken to investigate on a simple in vitro Calu-3 model the mechanisms involved in the transfer across epithelial cells of plutonium (Pu) and americium (Am) as a function of their intrinsic properties (nature, physicochemical form) or their association with serum proteins, inorganic ligands or synthetic chelating agents. Both the contribution of the transcellular and paracellular routes to the transfer of these various forms were studied. Results show that uptake of Pu and Am by epithelial cells is not positively correlated with their transfer, which suggests that radionuclides transcytosis is a continuous process in comparison with the quick translocation of Pu/Am-small size complexes. Furthermore, reducing epithelial cells paracellular permeability with the glucocorticoid hormone Dexamethasone (DEX) resulted into a lower transfer of Pu citrate, and of both actinides in the presence of diethylene triamine pentaacetic acid (DTPA) and 3,4,3-LI(1,2-HOPO). Taken together, these results seem to indicate that a paracellular pathway may be responsible, at least partly, for the higher pulmonary absorption observed in vivo for actinides bound to low-molecular weight ligands such as citrate, DTPA or HOPO.

肺吸收是控制锕系元素生物分布和吸入内部污染后毒性的时间依赖过程中的关键步骤。目前的研究是在一个简单的体外Calu-3模型上进行的，以研究钚（Pu）和镅（Am）的内在特性（性质、物理化学形式）或它们与血清蛋白、无机配体或合成螯合剂的关联在上皮细胞间转移的机制。研究了跨细胞和细胞旁途径对这些不同形式的转移的贡献。结果表明，上皮细胞对Pu和Am的摄取与它们的转移不呈正相关，这表明与Pu/Am小尺寸复合物的快速易位相比，放射性核素的胞吞作用是一个连续的过程。此外，糖皮质激素地塞米松（Dexamethasone， DEX）降低上皮细胞的细胞旁通透性，导致在二乙烯三胺五乙酸（DTPA）和3,4,3- li （1,2- hopo）存在下，柠檬酸Pu和两种锕系元素的转移降低。综上所述，这些结果似乎表明，细胞旁通路可能至少在一定程度上负责观察到锕系元素与低分子量配体（如柠檬酸盐、DTPA或HOPO）结合的较高肺吸收。

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引用次数: 0

Toxicity assessment of 6PPD-quinone in human lung cells: Insights from BEAS-2B and A549 cell lines 6ppd -醌对人肺细胞的毒性评价：来自BEAS-2B和A549细胞系的见解。

IF 2.7 3区医学 Q3 TOXICOLOGY

Toxicology in Vitro

Pub Date : 2025-09-17 DOI: 10.1016/j.tiv.2025.106147

Saja Damdam , Blake Hunnie , Parker Jones , Markus Hecker , Markus Brinkmann , Francisco C. da Silva Junior

N-(1,3-Dimethylbutyl)-N′-phenyl-p-phenylenediamine-quinone (6PPD-Q), an environmental transformation product of the rubber tire antioxidant 6PPD, is increasingly detected in urban environments, yet its impact on human health. This study investigated toxicological effects of 6PPD-Q in two human lung cells: BEAS-2B (a transformed bronchial epithelial cell) and A549 (a lung adenocarcinoma cell). Cells were exposed to 6PPD-Q at concentrations of 5 to 80 ng/mL and effects on cell viability, oxidative stress by generation of reactive oxygen species (ROS), disruption of antioxidant defense response, oxidative DNA damage as determined by formation of 8-hydroxy-2′-deoxyguanosine (8-OHdG), and biotransformation 6PPD-Q were determined. Results showed a biphasic response with an increase in cell viability at lower concentrations, suggesting an adaptive cellular response. ROS production and levels of 8-OHdG significantly increased, indicating an imbalance in redox status and induction of oxidative DNA damage. Two phase I hydroxylation products, 6PPD-Q-4-OH (TPOH1) and 6PPD-Q-phenyl-OH (TPOH2), were identified. In A549 cells, TPOH1 was only in the media, while TPOH2 was found both inside cells and in the media. Moreover, mRNA expression analysis revealed upregulation of metabolism- and oxidative stress-related genes and inflammatory cytokines. These findings suggest that 6PPD-Q may trigger oxidative stress and inflammation in lung cells. This study highlights the effects of 6PPD-Q on lung cells and underscores the need for further research on its long-term impact on human respiratory health.

N-（1,3-二甲基丁基）-N'-苯基-对苯二胺醌（6PPD- q）是橡胶轮胎抗氧化剂6PPD的环境转化产物，在城市环境中检测到的数量越来越多，但其对人体健康的影响却越来越大。本研究考察了6PPD-Q对两种人肺细胞BEAS-2B（转化支气管上皮细胞）和A549（肺腺癌细胞）的毒理学作用。细胞暴露于浓度为5 ~ 80 ng/mL的6PPD-Q中，观察其对细胞活力、活性氧（ROS）产生的氧化应激、抗氧化防御反应的破坏、8-羟基-2'-脱氧鸟苷（8-OHdG）形成的DNA氧化损伤以及6PPD-Q生物转化的影响。结果显示，在较低浓度下，细胞活力增加，呈双相反应，表明细胞有适应性反应。ROS生成和8-OHdG水平显著增加，表明氧化还原状态失衡，诱导DNA氧化损伤。鉴定出了6PPD-Q-4-OH （TPOH1）和6ppd - q -苯基oh （TPOH2）两个I相羟基化产物。在A549细胞中，TPOH1仅存在于培养基中，而TPOH2在细胞内和培养基中均存在。此外，mRNA表达分析显示代谢和氧化应激相关基因和炎症细胞因子上调。这些发现表明，6PPD-Q可能会引发肺细胞的氧化应激和炎症。这项研究强调了6PPD-Q对肺细胞的影响，并强调了进一步研究其对人类呼吸健康的长期影响的必要性。

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引用次数: 0

Use of resazurin-based metabolic assays as a continuous measure of viability in three-dimensional (3D) in vitro cell culture: A study with Presto Blue™ 使用瑞沙脲为基础的代谢测定作为三维（3D）体外细胞培养活力的连续测量：Presto Blue™的研究。

IF 2.7 3区医学 Q3 TOXICOLOGY

Toxicology in Vitro

Pub Date : 2025-09-16 DOI: 10.1016/j.tiv.2025.106127

Veronica M. Lucian, Robert C. Carlisle, Constantin C. Coussios, Malavika Nair

Testing cell viability in three-dimensional (3D) in vitro cell cultures is not always straightforward. Reduction-based metabolic assays have been suggested as a rapid, reportedly non-toxic mechanism for monitoring cell viability in continuous culture experiments. However, in 3D cultures these assays have been predominantly used semiquantitatively to indicate relative trends in viability. Obtaining quantitative values of cell number is often challenging, particularly when performing continuous measurements of viability when compared with end-point assessments. This work presents experiments performed to robustly identify and address the sources of inconsistency in existing Presto Blue™ methods for 3D cultures. Using human dermal fibroblasts (HDFs) as a model cell line seeded onto type I collagen scaffolds, we examine the impact of Presto Blue™ assays on reported cell numbers in 2D versus 3D cultures. We separate the impact of potential dye-induced toxicity from manipulation-induced cell detachment by considering the effects of passage number, incubation period, modifications of substrate chemistry and duration of total dye exposure as independent variables. The work presented includes a finalised protocol that demonstrates that while resazurin-based reduction assays remain a valuable tool for rapid assessment of cell metabolism and/or viability, additional considerations of the substrate and sampling frequencies are needed in 3D cultures to ensure accurate and reproducible results.

在三维（3D）体外细胞培养中测试细胞活力并不总是直截了当的。在连续培养实验中，基于还原的代谢测定被认为是一种快速的、据报道无毒的监测细胞活力的机制。然而，在三维培养中，这些检测主要是半定量地用于指示生存能力的相对趋势。获得细胞数量的定量值通常是具有挑战性的，特别是当与终点评估相比进行连续的活力测量时。这项工作介绍了进行的实验，以强有力地识别和解决现有Presto Blue™3D培养方法中不一致的来源。使用人真皮成纤维细胞（HDFs）作为模型细胞系，将其植入I型胶原支架上，我们检查了Presto Blue™检测对2D和3D培养中报告的细胞数量的影响。我们通过考虑传代数、孵育期、底物化学修饰和总染料暴露时间作为独立变量的影响，将潜在染料诱导毒性的影响与操作诱导的细胞脱离分开。提交的工作包括一个最终的协议，该协议表明，虽然基于瑞沙脲的还原测定仍然是快速评估细胞代谢和/或活力的有价值的工具，但在3D培养中需要额外考虑底物和采样频率，以确保准确和可重复的结果。

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引用次数: 0

The emerging pollutants polycyclic aromatic compounds (PAH'S) bisphenol a (BPA), and phthalates impair immune system function: Effects on human macrophages 新出现的污染物多环芳香族化合物（PAH’s）、双酚a （BPA）和邻苯二甲酸酯损害免疫系统功能：对人巨噬细胞的影响。

IF 2.7 3区医学 Q3 TOXICOLOGY

Toxicology in Vitro

Pub Date : 2025-09-05 DOI: 10.1016/j.tiv.2025.106145

K. Bobadilla-Lozoya , J. Morales-Montor , K.G. Mejía-Salgado , K.E. Nava-Castro

Human activity has led to the increment of diverse pollutants. Plastics have great practical value since they are present in everyday products. However, not only plastics have gained importance, but their plasticizers such as bisphenol A (BPA), phthalates and other chemicals such as the polyaromatic hydrocarbon compounds (PAHs) have described to impact in human and animal health because of its chronic exposure and that they are endocrine disruptors (EDs). Since immune cells express hormone receptors and AhR, they are susceptible to these EDs. We hypothesized that these compounds may alter their maturation and function. We focus on macrophages since they link the innate and adaptive immune response, playing different roles in disease. We cultured human monocytes in the presence of phthalates, bisphenol A or PAH's and analyze both maturation and function such as phagocytosis, antigen processing and antigen presentation. Our results show that these compounds affect differentially macrophage function, being the phtalates DEHP and DBP the ones that have the greatest impact. Both inhibit human macrophage maturation, observed by the lack of expression of MHC-II, CD80/86, which in consequence, impair antigen presentation and phagocytosis. BPA did not alter maturation but changed antigen processing activity while PAHs alter both antigen processing and presentation. These results may have great implications on human health and disease, since emergent pollutants affect normal macrophage function.

人类活动导致了各种污染物的增加。塑料有很大的实用价值，因为它们存在于日常用品中。然而，不仅塑料变得越来越重要，而且它们的增塑剂，如双酚A （BPA）、邻苯二甲酸酯和其他化学物质，如多芳烃化合物（PAHs），也被描述为对人类和动物健康的影响，因为它们长期接触，而且它们是内分泌干扰物（EDs）。由于免疫细胞表达激素受体和AhR，它们对这些ed很敏感。我们假设这些化合物可能会改变它们的成熟和功能。我们关注巨噬细胞，因为它们连接先天和适应性免疫反应，在疾病中发挥不同的作用。我们在邻苯二甲酸盐、双酚A或多环芳烃存在下培养人单核细胞，并分析其成熟和功能，如吞噬、抗原加工和抗原呈递。我们的研究结果表明，这些化合物对巨噬细胞功能的影响是不同的，其中邻苯二甲酸酯DEHP和DBP的影响最大。两者都抑制人巨噬细胞成熟，通过缺乏MHC-II， CD80/86的表达观察到，因此，损害抗原呈递和吞噬作用。BPA不改变成熟，但改变抗原加工活性，而PAHs改变抗原加工和呈递。这些结果可能对人类健康和疾病具有重要意义，因为新兴污染物会影响正常的巨噬细胞功能。

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