Toxicology in Vitro最新文献_第6页

Excess curcumin causes cytotoxicity of its nanoconjugate with nanoceria 过量的姜黄素引起其纳米结合物与纳米粒的细胞毒性

IF 2.7 3区医学 Q3 TOXICOLOGY

Toxicology in Vitro

Pub Date : 2025-09-03 DOI: 10.1016/j.tiv.2025.106144

Nikita N. Chukavin , Anton L. Popov , Victoria A. Anikina , Daria A. Vinnik , Boris A. Bokl , Nelli R. Popova

Curcumin is a natural bioactive substance with promising biomedical applications. However, the low solubility and stability of curcumin significantly limit its potential use. The development of nanoformulations of curcumin makes it possible to circumvent the above limitations. Cerium dioxide (CeO₂, NDC) nanoparticles are a promising platform for curcumin binding. They are able to absorb curcumin on their surface, providing increased bioavailability and bioaccumulation. Moreover, NDC have unique enzyme-like properties that can be used for targeted delivery and controlled release of curcumin. Meanwhile, the potential cytotoxicity of such nanoformulations remains poorly understood. In this work, we synthesized the NDC-curcumin nanoconjugate and investigated the effect of excess curcumin on the cytotoxicity of this nanoformulation. Curcumin has been shown to bind to the surface of nanoparticles, forming a colloidally stable nanoconjugate. At the same time, excess curcumin formed a separate nanoscale fraction, which caused the statistically significant cytotoxicity of the nanoconjugate in relation to human keratinocytes (HaCaT), mesenchymal stem cells (hMSc) and fibroblasts (HF). These cell lines represent the cells that form skin, mucous membranes, and connective tissue, with which curcumin nanoformulations can interact through various methods of administration. IC₅₀ values of curcumin and NDC-curcumin were 400 and 482 μM for HaCaT, 193 and 211 μM for hMSc, 266 and 304 μM for HF, respectively, after 72 h of coincubation. Consequently, NDC provided an increased biocompatibility of curcumin. Application of a rational design of curcumin nanoformulations can help to overcome possible limitations of its practical use due to its toxicity, enhancing its bioactivity.

姜黄素是一种具有生物医学应用前景的天然生物活性物质。然而，姜黄素的低溶解度和稳定性极大地限制了其潜在的应用。姜黄素纳米配方的发展使其有可能绕过上述限制。二氧化铈（CeO2， NDC）纳米颗粒是姜黄素结合的良好平台。它们能够吸收姜黄素在其表面，提供增加的生物利用度和生物积累。此外，NDC具有独特的酶样特性，可用于姜黄素的靶向递送和控释。同时，这种纳米制剂的潜在细胞毒性仍然知之甚少。本文合成了ndc -姜黄素纳米缀合物，并研究了过量姜黄素对其细胞毒性的影响。姜黄素已被证明与纳米颗粒表面结合，形成胶体稳定的纳米缀合物。同时，过量姜黄素形成单独的纳米级组分，导致纳米偶联物对人角质形成细胞（HaCaT）、间充质干细胞（hMSc）和成纤维细胞（HF）的细胞毒性具有统计学意义。这些细胞系代表了形成皮肤、粘膜和结缔组织的细胞，姜黄素纳米制剂可以通过各种给药方法与这些细胞相互作用。共孵育72 h后，HaCaT的IC50值分别为400 μM和482 μM， hMSc的IC50值分别为193 μM和211 μM， HF的IC50值分别为266 μM和304 μM。因此，NDC增加了姜黄素的生物相容性。合理设计姜黄素纳米制剂有助于克服其毒性对其实际应用的限制，提高其生物活性。

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引用次数: 0

NAM-based development of a predictive test model for evaluating skin mildness potential of rinse-off products via integrated in vitro assays 基于nama的预测测试模型的开发，通过综合体外分析来评估冲洗产品的皮肤温和性潜力。

IF 2.7 3区医学 Q3 TOXICOLOGY

Toxicology in Vitro

Pub Date : 2025-08-29 DOI: 10.1016/j.tiv.2025.106134

Yi-Peng Ng , Mei-Leng Tee , Shi-Ngar Pang, Chung-Lee Yee, Ursula Rho-Wan Chong, Khan-Loon Ng, Ka-Heng Lee, Mong-Sah Toh

The Forearm Controlled Application Test (FCAT) is widely used to assess skin irritancy and drying potential of rinse-off product but limited by its low throughput and long testing duration. To address these limitations, we explored the development of predictive models using New Approach Methodology (NAM) as a screening tool for evaluating skin mildness potential of rinse-off products. The skin irritancy and drying potential of standard surfactants were evaluated through multiple in vitro assays to identify relevant biomarkers, including a skin irritation bioassay by using Human Reconstituted Skin, a protein solubilization assay by using Zein test and a lipid solubilization assay by using Fatty Acid Methyl Ester (FAME) test. The in vitro test results were correlated to the clinical FCAT data, leading to the development of two multiple linear regression models in predicting changes of Transepidermal Water Loss (TEWL) and skin moisture parameters with R² of 0.7062 and 0.8270, respectively. The models achieved prediction accuracies of 100 % and 89 % with relatively low Mean Absolute Error (MAE), outperforming single biomarker model. In summary, this proof-of-concept study demonstrated potential of integrative predictive models to predict clinical outcomes of FCAT, serving as a valuable NAM tool for evaluating the safety and skin mildness potential of rinse-off formulation.

前臂控制应用试验（FCAT）被广泛用于评估冲洗产品的皮肤刺激性和干燥潜力，但受其低通量和测试时间长的限制。为了解决这些局限性，我们探索了使用新方法方法（NAM）作为评估冲洗产品的皮肤温和潜力的筛选工具的预测模型的发展。通过多种体外实验来评估标准表面活性剂的皮肤刺激性和干燥潜力，以确定相关的生物标志物，包括使用人重构皮肤进行皮肤刺激性生物试验，使用玉米蛋白试验进行蛋白质增溶试验，使用脂肪酸甲酯（FAME）试验进行脂质增溶试验。体外试验结果与临床FCAT数据相关，建立了预测经皮失水（TEWL）和皮肤水分参数变化的多元线性回归模型，R2分别为0.7062和0.8270。模型的预测精度分别为100 %和89 %，平均绝对误差（MAE）相对较低，优于单一生物标志物模型。总之，这项概念验证研究证明了综合预测模型预测FCAT临床结果的潜力，作为评估冲洗配方安全性和皮肤温和性潜力的有价值的NAM工具。

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引用次数: 0

Stronger prooxidative effects of chromium(VI) comparing to chromium(III) in endocrine and non-endocrine tissues with the thyroid being completely resistant to antioxidant protection 与铬（III）相比，铬（VI）在内分泌和非内分泌组织中的促氧化作用更强，甲状腺完全抵抗抗氧化保护

IF 2.7 3区医学 Q3 TOXICOLOGY

Toxicology in Vitro

Pub Date : 2025-08-26 DOI: 10.1016/j.tiv.2025.106132

Aleksandra K. Gładysz , Jan Stępniak , Laura López-Pingarrón , Joaquin J. Garcia , Małgorzata Karbownik-Lewińska

Chromium (Cr) is a harmful heavy metal pollutant. Cr(VI) is a group 1 carcinogen (carcinogenic to humans), whereas Cr(III) is a group 3 carcinogen (not classifiable as to its carcinogenicity to humans). Cr is also documented to be an endocrine disrupting chemical. The study aimed to check whether Cr(VI) compound (K₂Cr₂O₇) or Cr(III) compound (CrCl₃·6H₂O) induce oxidative damage to membrane lipids (lipid peroxidation, LPO) in homogenates of two endocrine (the thyroid and the ovary) and two non-endocrine (the kidney and the liver) tissues, and whether antioxidants, such as melatonin, indole-3-propionic acid (IPA) and 17β-estradiol, reveal protective effects. Of note, the healthy thyroid gland is characterized by relatively high oxidative stress. Porcine tissue homogenates were incubated in the presence of Cr(VI) (0.05–10.0 mM) or Cr(III) (5.0–200.0 mM) with/without melatonin (5 mM) or IPA (5 mM) or 17β-estradiol (1 mM). The malondialdehyde+4-hydroxyalkenals (MDA + 4-HDA) concentration (LPO index) was measured spectrophotometrically. Cr(VI) (≥0.1–1.25 mM) significantly increased LPO in all tissues but these damaging effects were not prevented by any antioxidant tested. In turn, Cr(III) (≥25 mM) also significantly increased LPO in all examined tissues. All antioxidants reduced Cr(III)-induced LPO in the ovary, kidney, and liver but had no protective effects in the thyroid. Our findings highlight chromium's strong prooxidative effects, especially in the thyroid. The inability of antioxidants to prevent Cr-induced damage, especially in the thyroid, underscores the need for further research to identify effective protective strategies.

铬是一种有害的重金属污染物。铬（VI）为1类致癌物（对人类有致癌性），而铬（III）为3类致癌物（对人类的致癌性不能分类）。铬也被证明是一种干扰内分泌的化学物质。本研究旨在检测Cr（VI）化合物（K2Cr2O7）或Cr（III）化合物（CrCl3·6H2O）是否诱导两种内分泌组织（甲状腺和卵巢）和两种非内分泌组织（肾脏和肝脏）均质液膜脂氧化损伤（脂质过氧化，LPO），以及褪黑素、吲哚-3-丙酸（IPA）和17β-雌二醇等抗氧化剂是否具有保护作用。值得注意的是，健康的甲状腺的特点是相对较高的氧化应激。猪组织匀浆在Cr(VI) （0.05-10.0 mM）或Cr(III) （5.0-200.0 mM）的存在下孵育，含/不含褪黑素（5 mM）或IPA （5 mM）或17β-雌二醇（1 mM）。分光光度法测定丙二醛+4-羟基醛（MDA + 4-HDA）浓度（LPO指数）。Cr(VI)（≥0.1-1.25 mM）显著增加了LPO在所有组织中的作用，但这些损伤作用并没有被任何抗氧化剂所阻止。反过来，Cr(III)（≥25 mM）也显著增加了所有检查组织的LPO。所有抗氧化剂都能降低卵巢、肾脏和肝脏中Cr（III）诱导的LPO，但对甲状腺没有保护作用。我们的发现强调了铬的强抗氧化作用，特别是在甲状腺中。抗氧化剂无法预防铬引起的损伤，特别是在甲状腺，强调需要进一步研究以确定有效的保护策略。

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引用次数: 0

Hyperuricemia impairs endothelial function through SMS2-dependent activation of the endoplasmic reticulum stress response 高尿酸血症通过sms2依赖性的内质网应激反应激活损害内皮功能。

IF 2.7 3区医学 Q3 TOXICOLOGY

Toxicology in Vitro

Pub Date : 2025-08-25 DOI: 10.1016/j.tiv.2025.106133

Liyuan Wang, Ruifang Zhang, Xuelian Liu

Hyperuricemia is a recognized risk factor for cardiovascular diseases, including peripheral arterial disease (PAD), though molecular mechanisms linking uric acid to endothelial dysfunction remain unclear. This study investigates the role of sphingomyelin synthase 2 (SMS2) and endoplasmic reticulum (ER) stress in uric acid-induced endothelial impairment. Human umbilical vein endothelial cells were exposed to physiologically relevant concentrations of uric acid, with SMS2 function modulated through siRNA knockdown and ER stress inhibited using 4-phenylbutyric acid. Uric acid exhibited concentration-dependent cytotoxicity (IC50 ∼ 9 mg/dL) and significantly upregulated SMS2 expressions. At this concentration, uric acid significantly increased apoptosis, impaired migratory capacity, and diminished angiogenic potential (p < 0.01). These functional deficits coincided with marked elevation of ER stress markers and intracellular calcium disruption. Notably, both SMS2 knockdown and ER stress inhibition substantially reversed these uric acid-induced endothelial dysfunctions, restoring cell survival, migration, and angiogenic capacity while normalizing ER stress markers and calcium homeostasis (p < 0.01). These findings identify SMS2 as a potential therapeutic target for vascular complications in hyperuricemia and suggest ER stress modulators may protect against uric acid-induced endothelial damage.

高尿酸血症是公认的心血管疾病的危险因素，包括外周动脉疾病（PAD），尽管尿酸与内皮功能障碍之间的分子机制尚不清楚。本研究探讨了鞘磷脂合成酶2 （SMS2）和内质网应激在尿酸诱导的内皮损伤中的作用。人脐静脉内皮细胞暴露于与生理相关浓度的尿酸中，SMS2功能通过siRNA敲低调节，内质网应激通过4-苯基丁酸抑制。尿酸表现出浓度依赖性的细胞毒性（IC50 ~ 9 mg/dL）和显著上调SMS2表达。在此浓度下，尿酸显著增加细胞凋亡，损害迁移能力，降低血管生成潜能(p

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引用次数: 0

Cytotoxic and immunotoxic profile of HgCl2 involves alterations in purinergic signaling through the P2X7/NLRP3/CASP-1/IL-1β pathway: An in vitro study using human blood immune cells HgCl2的细胞毒性和免疫毒性谱涉及通过P2X7/NLRP3/CASP-1/IL-1β途径改变嘌呤能信号：一项使用人血液免疫细胞的体外研究

IF 2.7 3区医学 Q3 TOXICOLOGY

Toxicology in Vitro

Pub Date : 2025-08-19 DOI: 10.1016/j.tiv.2025.106131

Mairin Schott , Charles Elias Assmann , Bianca Vedoin Copês Rambo , Marcylene Vieira da Silveira , Milagros Fanny Vera Castro , Vitor Bastianello Mostardeiro , Adriel Antônio Schirmann , Robson Lourenço da Silva Santos , Pâmela de Almeida Milioni , Ana Barbosa Viana , Valderi Luiz Dressler , Daniel Lázaro Gallindo Borges , Nilda Berenice de Vargas Barbosa , Vera Maria Melchiors Morsch , Michael Aschner , João Batista Teixeira da Rocha , Maria Rosa Chitolina Schetinger

An in vitro model using human peripheral blood mononuclear cells (PBMCs) was established to investigate the cytotoxic, oxidative and inflammatory effects and changes in purinergic system parameters caused by mercuric chloride (HgCl₂). Cells were exposed to concentrations of HgCl₂ (0.05, 0.5, 5, and 50 μM) for 24, 48 and 72 h. Cell viability was measured by trypan blue and MTT assays, and IC₅₀; apoptosis and cell death were assessed by flow cytometry. Oxidative stress was evaluated by reactive species (RS) generation, determination of Mercury (ICP-MS), Nitric Oxide (NO), and lipid peroxidation. Increased levels of HgCl₂ induced RS generation, NO, lipid peroxidation, apoptosis, and altered the cell cycle, reducing DNA synthesis and cell division of PBMCs. Flow cytometry confirmed decreased viability and increased late apoptosis. HgCl₂ accumulation in PBMCs was confirmed by ICP-MS. HgCl₂ altered purinergic system components, inhibiting NTPDase and increasing ADA activity. At 5 μM, it increased gene expression of purinergic receptors and both anti-inflammatory (IL-10) and pro-inflammatory markers (IL-1β, IL-6, TNF-α, NLRP3, CASP-1, NF-κB). Overexpression of the P2X7/NLRP3/CASP-1/IL-1β axis triggered cell death by pyroptosis. These findings provide compelling evidence HgCl₂ induces cytotoxic and inflammatory effects in PBMCs.

采用人外周血单核细胞（PBMCs）建立体外模型，研究氯化汞（HgCl2）对细胞毒、氧化和炎症的影响以及嘌呤能系统参数的变化。将细胞暴露于浓度为0.05、0.5、5和50 μM的HgCl2中24、48和72 h。采用台锥蓝法和MTT法测定细胞活力，IC50；流式细胞术检测细胞凋亡和细胞死亡。通过活性物质（RS）的生成、汞（ICP-MS）、一氧化氮（NO）和脂质过氧化测定来评估氧化应激。HgCl 2水平升高可诱导RS生成、NO、脂质过氧化、细胞凋亡，改变细胞周期，减少DNA合成和细胞分裂。流式细胞术证实细胞活力下降，晚期细胞凋亡增加。ICP-MS证实了pbmc中HgCl 2的积累。HgCl 2改变嘌呤能系统成分，抑制ntpase和增加ADA活性。5 μM时，嘌呤能受体基因表达增加，抗炎（IL-10）和促炎标志物（IL-1β、IL-6、TNF-α、NLRP3、CASP-1、NF-κB）表达增加。P2X7/NLRP3/CASP-1/IL-1β轴的过表达引发细胞焦亡。这些发现提供了令人信服的证据，证明HgCl2在pbmc中诱导细胞毒性和炎症作用。

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引用次数: 0

Computational and spectrofluorimetric validation on glyphosate interactions with zebrafish (Danio rerio) acetylcholinesterase: Mechanistic and ecotoxicological implications 计算和荧光法验证草甘膦与斑马鱼乙酰胆碱酯酶的相互作用：机制和生态毒理学意义。

IF 2.7 3区医学 Q3 TOXICOLOGY

Toxicology in Vitro

Pub Date : 2025-08-14 DOI: 10.1016/j.tiv.2025.106130

Andressa Rubim Lopes , Michael González-Durruthy , Maria Natália D.S. Cordeiro , Ana S. Moura , Ramón Rial , Juan M. Ruso , Juliana Zomer Sandrini , Carlos Eduardo da Rosa , Camila de Martinez Gaspar Martins

This study explores the toxicodynamics of glyphosate in zebrafish (Danio rerio) acetylcholinesterase (zf-AChE) using a combined computational and experimental approach to reveal its potential cholinergic neurotoxic effects. Computational modeling suggested that glyphosate could block critical amino acid residues in the zf-AChE binding site, disrupting acetylcholine positioning and potentially leading to its pathological accumulation in cholinergic synapses. Additionally, glyphosate may adversely impact zf-AChE's flexibility, inducing conformational rigidity via hydrophobic van der Waals and hydrogen-bond interactions. These effects mirrored the binding behavior of physostigmine, a known specific zf-AChE inhibitor. Interestingly, the structural similarity between zf-AChE and human AChE (hs-AChE) suggests potential neurotoxicity in humans. Spectrofluorimetry confirmed binding between glyphosate and hs-AChE, resembling physostigmine binding. To sum up, our findings provide insights into glyphosate-induced cholinergic neurotoxicity in zebrafish, supporting extrapolations to humans and contributing valuable insights for ecotoxicology, new approach methodologies, and environmental risk assessment.

本研究采用计算和实验相结合的方法探讨草甘膦对斑马鱼乙酰胆碱酯酶（zf-AChE）的毒性动力学，以揭示其潜在的胆碱能神经毒性作用。计算模型表明，草甘膦可以阻断zf-AChE结合位点的关键氨基酸残基，破坏乙酰胆碱的定位，并可能导致其在胆碱能突触中的病理积累。此外，草甘膦可能会对zf-AChE的柔韧性产生不利影响，通过疏水范德华和氢键相互作用诱导构象刚性。这些效应反映了一种已知的特异性zf-AChE抑制剂——蛇毒碱的结合行为。有趣的是，zf-AChE和人类AChE （hs-AChE）之间的结构相似性表明对人类有潜在的神经毒性。荧光光谱法证实草甘膦与hs-AChE结合，类似于毒豆碱结合。综上所述，我们的研究结果为草甘膦诱导的斑马鱼胆碱能神经毒性提供了见解，促进了对人类的外推，并为生态毒理学、新方法方法和环境风险评估提供了有价值的见解。

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引用次数: 0

Transcriptomic points of departure for 6PPD-Quinone derived from human Caco-2 and HepG2 cells 来自人Caco-2和HepG2细胞的6ppd -醌的转录组学起点。

IF 2.7 3区医学 Q3 TOXICOLOGY

Toxicology in Vitro

Pub Date : 2025-08-14 DOI: 10.1016/j.tiv.2025.106129

Ke Xu, Krittika Mittal, Niladri Basu

N-(1,3-Dimethyl butyl)-N′-phenyl-phenylenediamine-quinone (6ppd-quinone) is of emerging concern due to its widespread presence and toxicity to aquatic species. The chemical has been detected in human biofluids though little is known about its effects on human tissues. The objective of this study was to increase understanding of 6ppd-quinone's potential human health effects by deriving transcriptomic points of departure (tPOD) values in two human cell lines using the TPD-seq workflow. An EC20 for cytotoxicity was calculated for Caco-2 (104 μg/L) but not for HepG2 cells. Even in the absence of cytotoxicity, tPOD values (20th gene, 10th percentile, mode) were calculated in Caco-2 (6.5-25 μg/L) and HepG2 (0.36-35 μg/L) cells. These ranges capture values from 16 statistical and bioinformatic tests that examined mapping methods (CLC and Deplexer), algorithms (Limma and DESeq2), and filters (log2FC and BMR). The most common and sensitive genes with calculable benchmark doses (BMDs) in Caco-2 (DPF2, CD44, PGAP1, GDF15, H4C16) and HepG2 (SLC5A3, DKK1, ARG2, PHLDA1, TM4SF1) cells are listed. Pathway BMDs were also calculated for Caco-2 (systemic lupus erythematosus, 9.7-18 μg/L; alcoholism, 9.7-20 μg/L; viral carcinogenesis, 9.3–18.1 μg/L), and HepG2 (metabolic pathways, 50-60 μg/L) cells. These findings highlight TPD-seq as an efficient workflow to yield quantitative and mechanistic data relevant for human health risk assessment.

N-（1,3-二甲基丁基）-N'-苯基-苯二胺醌（6PPD-Q）由于其广泛存在和对水生物种的毒性而引起了人们的关注。这种化学物质已在人体生物体液中检测到，但对其对人体组织的影响知之甚少。本研究的目的是通过使用TPD-seq工作流程在两种人类细胞系中获得转录组起始点（tPOD）值，从而增加对6PPD-Q对人类健康的潜在影响的理解。计算Caco-2的细胞毒性EC20(104 μg/L)，但不计算HepG2细胞的EC20。即使在没有细胞毒性的情况下，计算Caco-2（6.5-25 μg/L）和HepG2（0.36-35 μg/L）细胞的tPOD值（第20个基因，第10百分位，模式）。这些范围从16个统计和生物信息学测试中获取值，这些测试检查了映射方法（CLC和Deplexer）、算法（Limma和DESeq2）和过滤器（log2FC和BMR）。列出Caco-2 （DPF2、CD44、PGAP1、GDF15、H4C16）和HepG2 （SLC5A3、DKK1、ARG2、PHLDA1、TM4SF1）细胞中可计算基准剂量（bmd）最常见和最敏感的基因。计算Caco-2（系统性红斑狼疮）的通路bmd， 9.7-18 μg/L；酗酒,-20 9.7μg / L;病毒致癌作用，9.3-18.1 μg/L)和HepG2（代谢途径，50-60 μg/L）细胞。这些发现强调了TPD-seq是一种有效的工作流程，可以产生与人类健康风险评估相关的定量和机制数据。

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引用次数: 0

Inhibitory potential of phytochemicals on species-specific breast cancer resistance protein transport activity 植物化学物质对物种特异性乳腺癌抗性蛋白运输活性的抑制潜力。

IF 2.7 3区医学 Q3 TOXICOLOGY

Toxicology in Vitro

Pub Date : 2025-08-10 DOI: 10.1016/j.tiv.2025.106128

Lérica le Roux-Pullen , Jeroen J.M.W. van den Heuvel , Ilse R. Dubbelboer , Frans G.M. Russel , Ronette Gehring , Jan B. Koenderink

The use of herbal alternatives in modern agriculture and healthcare offers a sustainable approach to animal and human health, but raises concerns about safety, particularly regarding phytochemical interactions at membrane transport proteins. Phytochemicals – bioactive compounds found in herbs - can influence the function of the breast cancer resistance protein (BCRP/ABCG2). BCRP is a key efflux transporter in mammals and in particularly abundant in the blood-milk-barrier of lactating animals, with the potential to affect milk quality and safety. This study investigates species-specific interactions of eight selected phytochemicals with BCRP orthologs in humans, cows, sheep and goats, using a transport assay with membrane vesicles derived from species-specific BCRP-overexpressing HEK293 cells. Five phytochemicals, namely apigenin, berberine, kaempferol, N-isobutyldodeca-2E4E8Z10E/Z-tetraenamide and quercetin inhibited BCRP-mediated transport of its prototypic substrate [³H]estrone sulfate by more than 30 % in all species. IC₅₀ values and, assuming competitive inhibition, Ki values were calculated for these compounds. Apigenin and kaempferol were the most potent inhibitors with Ki values <0.1 μM in all species, while N-isobutyldodeca-2E4E8Z10E/Z-tetraenamide was the weakest inhibitor (Ki > 30 μM). No significant interspecies differences in inhibitory potency were observed. Understanding the cross-species effects of bioactive compounds on BCRP activity is essential for predicting their broader biological impacts. Similar inhibition trends across species facilitate interspecies extrapolation and minimize the amount of animal studies needed to further investigate the effect of these phytochemicals on milk composition.

在现代农业和医疗保健中使用草药替代品为动物和人类健康提供了一种可持续的方法，但也引起了对安全性的担忧，特别是在膜运输蛋白上的植物化学相互作用方面。植物化学物质——在草药中发现的生物活性化合物——可以影响乳腺癌抵抗蛋白（BCRP/ABCG2）的功能。BCRP是哺乳动物体内一种重要的外排转运蛋白，在哺乳期动物的血乳屏障中含量尤其丰富，具有影响乳汁质量和安全的潜力。本研究利用来自物种特异性BCRP过表达HEK293细胞的膜泡运输实验，研究了8种选定的植物化学物质与人、牛、绵羊和山羊中BCRP同源物的物种特异性相互作用。5种植物化学物质，即芹菜素、小檗碱、山奈酚、n -异丁基十二烷- 2e4e8z10e / z -四烯酰胺和槲皮素，在所有物种中抑制bcrp介导的原型底物[3H]雌酮硫酸盐的运输超过30% %。计算了这些化合物的IC50值，并假设了竞争抑制作用，计算了Ki值。芹菜素和山奈酚是最有效的抑制剂，Ki值为 30 μM)。抑菌效力在种间无显著差异。了解生物活性化合物对BCRP活性的跨物种影响对于预测其更广泛的生物学影响至关重要。跨物种的类似抑制趋势促进了物种间的外推，并减少了进一步研究这些植物化学物质对牛奶成分影响所需的动物研究数量。

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引用次数: 0

Isolation and characterization of bovine Limbal mesenchymal stromal cells for application in ocular toxicity studies 牛角膜缘间充质间质细胞的分离与鉴定及其在眼毒性研究中的应用

IF 2.7 3区医学 Q3 TOXICOLOGY

Toxicology in Vitro

Pub Date : 2025-07-30 DOI: 10.1016/j.tiv.2025.106125

Martina Daniela Benedetti , Mariela Lenze , Mora Renée García , Sofía Fátima Magaña Guerrero , Silvia Wikinski , Yonathan Garfias , María Laura Gutiérrez

Ocular toxicity assessment is essential to ensure the safety of chemicals and human-use products. Although the Draize test in rabbits has historically been the regulatory standard, it presents significant ethical and scientific limitations. While validated in vitro methods are currently available, most of them do not allow the evaluation of damage reversibility—a key parameter for hazard classification under the United Nations Globally Harmonized System (UN GHS).

This study evaluates the utility of an in vitro model based on limbal mesenchymal stromal cells (LMSC) for ocular toxicity testing and the prediction of corneal damage reversibility. LMSC were obtained from slaughterhouse-derived residual tissue, cultured under specific conditions, and briefly exposed to substances classified according to UN GHS. Cell migration was then assessed as an indicator of tissue recovery.

This preliminary report presents, to our knowledge, the first application of short-term (5-min) exposure in a scratch assay to evaluate its effect on migration capacity. Unlike previous studies relying on prolonged exposure to inhibitory compounds, this approach better simulates accidental ocular exposure scenarios. While migration was not significantly disrupted under the tested conditions, these results offer valuable insight into the relationship between viability and wound healing and highlight the importance of exposure time and concentration in in vitro ocular toxicity models. Overall, this work establishes a promising foundation for future refinement of alternative methods that aim to predict damage persistence and reversibility more accurately.

眼毒性评估对于确保化学品和人类使用产品的安全性至关重要。尽管在兔子身上进行的Draize试验在历史上一直是监管标准，但它存在重大的伦理和科学局限性。虽然目前已有体外验证方法，但大多数方法不允许评估损害可逆性——这是联合国全球协调系统（UN GHS）危害分类的关键参数。本研究评估了基于角膜缘间充质间质细胞（LMSC）的体外模型在眼毒性测试和角膜损伤可逆性预测中的实用性。LMSC是从屠宰场衍生的残余组织中获得的，在特定条件下培养，并短暂暴露于根据联合国GHS分类的物质。然后将细胞迁移作为组织恢复的指标进行评估。据我们所知，本初步报告首次在划痕试验中应用短期（5分钟）暴露来评估其对迁移能力的影响。与以往依赖于长时间暴露于抑制化合物的研究不同，这种方法更好地模拟了意外的眼部暴露情景。虽然在测试条件下迁移没有明显中断，但这些结果为研究存活能力和伤口愈合之间的关系提供了有价值的见解，并强调了在体外眼毒性模型中暴露时间和浓度的重要性。总的来说，这项工作为未来改进旨在更准确地预测损伤持久性和可逆性的替代方法奠定了有希望的基础。

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引用次数: 0

Cytotoxic effects of a LED/UV nail polish dryer in human keratinocytes LED/UV指甲油干燥器对人角质形成细胞的细胞毒性作用。

IF 2.7 3区医学 Q3 TOXICOLOGY

Toxicology in Vitro

Pub Date : 2025-07-29 DOI: 10.1016/j.tiv.2025.106124

Alexandra Lopes, Patrícia Pereira, Helena Oliveira

Nail polish dryers are radiation-emitting devices designed to dry and cure nail polishes. These devices primarily emit radiation within the ultraviolet A (UVA) range, with some also emitting visible light, particularly those equipped with light-emitting diodes (LEDs). The increasing use of nail polish dryers, combined with scientific concerns regarding the potential effects of UVA radiation on human skin, has raised significant safety questions. Recent studies have demonstrated cytotoxic, genotoxic and mutagenic effects in both human and murine cells. When these findings are considered alongside earlier reports linking the use of these devices to skin cancer, there is a clear need for a broader evaluation of their potential health impacts. This study aimed to evaluate the effects of realistic radiation exposures, when considering the actual gel-nail application process, on cell viability and intracellular reactive oxygen species (ROS) levels, in human keratinocytes. Cytotoxic effects were confirmed, with cell mortality rates exceeding 95 % and intracellular ROS levels increasing by over 250 % (72 h post-exposure), depending on the positioning of the cell culture within the device. These results underscore the need for a more thorough characterization of the cytotoxic effects caused by the radiation emitted by nail polish dryers.

指甲油烘干机是一种辐射装置，用于干燥和固化指甲油。这些设备主要发射紫外线A （UVA）范围内的辐射，其中一些也发射可见光，特别是那些配备了发光二极管（led）的设备。越来越多的人使用指甲油烘干机，再加上科学界对UVA辐射对人体皮肤的潜在影响的担忧，引发了重大的安全问题。最近的研究表明，在人类和小鼠细胞中都有细胞毒性、基因毒性和诱变作用。当这些发现与早期将这些设备的使用与皮肤癌联系起来的报告一起考虑时，显然需要对其潜在的健康影响进行更广泛的评估。本研究旨在评估实际辐射暴露对人角质形成细胞细胞活力和细胞内活性氧（ROS）水平的影响，同时考虑实际凝胶钉应用过程。细胞毒性效应得到证实，细胞死亡率超过95% %，细胞内ROS水平增加超过250 %（暴露后72 小时），这取决于细胞培养物在装置内的位置。这些结果强调需要更彻底地表征由指甲油烘干机发出的辐射引起的细胞毒性效应。

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引用次数: 0