Toxicology in Vitro最新文献_第4页

The Nrf2 activator tBHQ inhibits dendritic cell maturation and activation in response to bacterial and viral stimuli Nrf2激活因子thbhq抑制树突状细胞在细菌和病毒刺激下的成熟和激活。

IF 2.7 3区医学 Q3 TOXICOLOGY

Toxicology in Vitro

Pub Date : 2025-10-15 DOI: 10.1016/j.tiv.2025.106169

Saamera Awali , Yining Jin , David M. Duriancik , Cheryl E. Rockwell

Dendritic cells (DCs) are professional antigen presenting cells that promote both innate and adaptive immune responses. Pertinent to adaptive immunity, DCs activate naïve T cells by presenting peptides on MHC class II molecules. Tert-butylhydroquinone (tBHQ) is a widely used food additive and a potent activator of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2). Studies from our lab demonstrated that tBHQ impedes CD4 and CD8 T cell activation and effector function, but the effects of tBHQ on dendritic cell function remain unclear. To address this, splenic DCs were collected from wildtype C57BL/6 mice and treated with tBHQ (0.5 or 1 μM) for 30 mins prior to activation with either LPS or influenza A virus for 24 h. tBHQ treatment led to a significant decrease in the expression of the MHC class II receptor, CD80 and CD86, suggesting tBHQ may negatively impact DC maturation and activation. In addition, tBHQ inhibited secretion of IL-6, and to a lesser extent, TNFα, by LPS and IAV-activated DCs. Overall, our data suggest that tBHQ inhibits the expression of proteins important for DC function, which could ultimately have a negative impact on T cell response to pathogen.

树突状细胞（dc）是一种专业的抗原呈递细胞，可促进先天性和适应性免疫反应。与适应性免疫相关，dc通过在MHC II类分子上呈递肽来激活naïve T细胞。叔丁基对苯二酚（tBHQ）是一种广泛使用的食品添加剂，也是转录因子核因子-红细胞2相关因子- 2 （Nrf2）的有效激活剂。我们实验室的研究表明，thbhq阻碍CD4和CD8 T细胞的激活和效应功能，但thbhq对树突状细胞功能的影响尚不清楚。为了解决这个问题，从野生型C57BL/6小鼠中收集脾脏dc，在LPS或甲型流感病毒激活24 小时之前，用tBHQ（0.5或1 μM）处理30分钟。tBHQ处理导致MHC II类受体CD80和CD86的表达显著降低，提示tBHQ可能对DC的成熟和激活产生负面影响。此外，thbhq抑制LPS和iav激活的dc分泌IL-6，并在较小程度上抑制TNFα的分泌。总的来说，我们的数据表明，thbhq抑制DC功能重要蛋白的表达，这可能最终对T细胞对病原体的反应产生负面影响。

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引用次数: 0

Effect of extraction vehicles on medical device sensitization testing by LuSens assay 提取载体对LuSens法医疗器械敏化试验的影响。

IF 2.7 3区医学 Q3 TOXICOLOGY

Toxicology in Vitro

Pub Date : 2025-10-14 DOI: 10.1016/j.tiv.2025.106167

L. Svobodova , E. Pacalova , K. Kejlova , A. Vlkova , M. Dvorakova , M. Rucki , D. Jirova , H. Bendova

Skin sensitization risk of medical devices (MDs) has to be assessed before their marketing and clinical use. The obligatory methods (ISO 10993-10:2021) include exclusively in vivo tests, however, validated non-animal methods might be utilized after successful verification of their applicability in the specific field of MDs and their extracts. One of the candidate in vitro tests is the LuSens assay (OECD TG 442D), which covers the Key Event 2 (activation of keratinocytes) in the Adverse Outcome Pathway for Skin Sensitization. The aim of this pilot study was to share the experience gained during optimization of this method for testing of real-life MD extracts. We have confirmed that the extraction vehicles recommended in ISO10993-12:2021, could be considered for use in the LuSens assay, as they do not interfere with Luciferase induction. However, the preferred use of culture medium with serum as extraction vehicle for cytotoxicity tests was not optimal, as the fetal bovine serum (FBS) content significantly increased the LuSens cell viability, which biased the sensitization results. The study showed the presence of different content of leachable cytotoxic substances in the extracts depending on the type of extraction vehicle, particularly in case of metallic products. Further research will be necessary to identify the optimal extraction conditions for specific materials or devices.

医疗器械（MDs）的皮肤致敏风险必须在其上市和临床使用之前进行评估。强制性方法（ISO 10993-10:2021）仅包括体内试验，然而，经过验证的非动物方法在成功验证其在特定MDs及其提取物领域的适用性后，可以使用。其中一个候选的体外试验是LuSens试验（OECD TG 442D），它涵盖了皮肤致敏不良结果通路中的关键事件2（角质形成细胞的激活）。本初步研究的目的是分享在优化该方法测试真实的MD提取物过程中获得的经验。我们已经确认，iso10993 - 12:21 21中推荐的提取载体可以考虑用于LuSens试验，因为它们不会干扰荧光素酶的诱导。然而，首选使用血清培养基作为细胞毒性试验的提取载体并不是最佳的，因为胎牛血清（FBS）含量显著提高了LuSens细胞的活力，这对致敏结果有偏置。研究表明，根据提取工具的类型，萃取物中可浸出的细胞毒性物质含量不同，特别是在金属产品的情况下。需要进一步的研究来确定特定材料或设备的最佳提取条件。

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引用次数: 0

Particulate matter exposure-induced cholesterol metabolism dysregulation in lung epithelial cells 颗粒物暴露诱导的肺上皮细胞胆固醇代谢失调。

IF 2.7 3区医学 Q3 TOXICOLOGY

Toxicology in Vitro

Pub Date : 2025-10-14 DOI: 10.1016/j.tiv.2025.106164

Huanxiang Li , Yimin Li , Xiaozhen Wang , Zhiqian Zhong , Yadang Kuang , Jiaxuan Huang

Particulate matter (PM) poses a significant threat to human health, yet its systemic impact on molecular networks and cellular toxicity remains poorly understood. RNA sequencing was employed to explore the molecular mechanisms of micrometer-sized PMs obtained from air near the Yellow River on mink lung epithelial cells. PM particles were first characterized using scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and infrared spectra (IR) to examine morphology and elemental components. Then, the cellular toxicity of PM was examined using the CCK8 method. Results of gene ontology (GO) analysis and gene set enrichment analysis (GSEA) were confirmed using qRT-PCR of cholesterol homeostasis-related genes and free cholesterol measurements. PM exhibited dose-dependent inhibition of proliferation. Bioinformatics analysis indicated that 190 downregulated and 56 upregulated genes were identified after high-dose exposure to PM particles. The cholesterol metabolism pathway was substantially downregulated. The intrinsic mechanism driving the dysfunction of cholesterol metabolism was identified as oxidative stress, confirmed by measurements of reactive oxygen species (ROS), mitochondrial membrane potential, and the characterization of GSSG/GSH and NADP/NADPH ratios. The study highlights the link between PM-induced oxidative stress, impaired cholesterol homeostasis, and potential respiratory diseases, offering new insights into PM's physiological impact on lung cells.

颗粒物（PM）对人类健康构成重大威胁，但其对分子网络和细胞毒性的系统性影响仍知之甚少。采用RNA测序的方法，探讨了从黄河附近空气中获得的微米大小的pmms对水貂肺上皮细胞的分子机制。首先使用扫描电子显微镜（SEM）， x射线光电子能谱（XPS）和红外光谱（IR）来检测PM颗粒的形态和元素成分。然后用CCK8法检测PM的细胞毒性。基因本体（GO）分析和基因集富集分析（GSEA）结果通过胆固醇稳态相关基因的qRT-PCR和游离胆固醇测量得到证实。PM表现出剂量依赖性的增殖抑制作用。生物信息学分析表明，高剂量PM暴露后，共鉴定出190个下调基因和56个上调基因。胆固醇代谢途径明显下调。通过测量活性氧（ROS）、线粒体膜电位以及GSSG/GSH和NADP/NADPH比值，我们确定了驱动胆固醇代谢功能障碍的内在机制是氧化应激。该研究强调了PM诱导的氧化应激、胆固醇稳态受损和潜在呼吸系统疾病之间的联系，为PM对肺细胞的生理影响提供了新的见解。

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引用次数: 0

Assessment of ocular irritation potential of moisturizing and sunscreen cosmetic creams marketed in Algeria using the HET-CAM test 使用et - cam测试评估阿尔及利亚市场上销售的保湿和防晒护肤霜的眼部刺激潜力。

IF 2.7 3区医学 Q3 TOXICOLOGY

Toxicology in Vitro

Pub Date : 2025-10-14 DOI: 10.1016/j.tiv.2025.106168

Mecheri Imane , Djafer Rachid , Belmahi Mohamed Habib

Cosmetic products applied around the eyes, such as moisturizing and sunscreen creams, can come into contact with the conjunctiva, potentially causing irritation due to the thinness of the ocular epithelium. These products, widely used by the general population, remain in contact with the skin for extended periods. In this study, 41 cosmetic creams marketed in Algeria (moisturizers and sunscreens) were evaluated using the Hen's Egg Test on the Chorioallantoic Membrane (HET-CAM), an alternative to the Draize test. The results showed that 36.6 % of the tested creams induced irritation, with varying degrees of severity. Moisturizing creams were more frequently associated with irritation (44.0 %) compared to sunscreens (25.0 %). Among products intended for children, 44.4 % elicited an irritation response, and 60 % of irritating products carried the precautionary statement “avoid contact with eyes.” These findings provide the first data on the ocular irritation potential of cosmetic creams available in the Algerian market and contribute to regional safety assessment by identifying specific product categories with irritant potential.

涂抹在眼周的化妆品，如保湿霜和防晒霜，可能会接触到结膜，由于眼上皮薄，可能会引起刺激。这些产品被普通人群广泛使用，它们与皮肤的接触时间很长。在这项研究中，在阿尔及利亚销售的41种面霜（保湿霜和防晒霜）使用绒毛尿囊膜上的鸡蛋测试（et - cam）进行评估，这是Draize测试的一种替代方法。结果显示，36.6 %的测试面霜引起了不同程度的刺激。与防晒霜（25.0 %）相比，保湿霜更容易引起刺激（44.0 %）。在针对儿童的产品中，44.4% %引起刺激反应，60% %的刺激性产品带有“避免接触眼睛”的预防声明。这些发现提供了关于阿尔及利亚市场上可用的化妆品面霜的眼部刺激潜力的第一批数据，并通过确定具有刺激潜力的特定产品类别，有助于区域安全评估。

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引用次数: 0

Corrigendum to “The pesticide fungicide difenoconazole modulates the biophysical properties of sodium channel Nav1.5” [Toxicology in vitro, 2025, 106152] 农药杀菌剂二苯醚康唑调节钠通道Nav1.5的生物物理性质[j].体外毒理学，2025,106152。

IF 2.7 3区医学 Q3 TOXICOLOGY

Toxicology in Vitro

Pub Date : 2025-10-14 DOI: 10.1016/j.tiv.2025.106154

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

引用次数: 0

Neuromodulatory efficacy of Bacopa monniera extract against streptozotocin-induced neuronal dysfunction in SH-SY5Y cells: Implications for diabetic neuropathy 假马齿苋提取物对链脲佐菌素诱导的SH-SY5Y细胞神经功能障碍的神经调节作用：对糖尿病神经病变的影响。

IF 2.7 3区医学 Q3 TOXICOLOGY

Toxicology in Vitro

Pub Date : 2025-10-13 DOI: 10.1016/j.tiv.2025.106166

H.S. Bhumika , M.D. Pandareesh

Diabetic neuropathy (DN), a major complication of diabetes mellitus, is characterized by progressive neuronal damage driven by hyperglycemia-induced oxidative stress, mitochondrial dysfunction, and advanced glycation end product (AGE) accumulation. Bacopa monniera (Scrophulariaceae), enriched with the neuroactive saponin Bacoside A (BA), has demonstrated neuroprotective potential. This study explored the molecular mechanisms underlying the neuroprotective effects of B. monniera extract (BME) against streptozotocin (STZ)-induced toxicity in SH-SY5Y neuroblastoma cells. In silico ADMET analysis revealed that BA and its sapogenins possess favorable pharmacokinetic profiles, including enhanced absorption, reduced toxicity, and improved clearance, supporting their bioactive role in BME. Pretreatment with BME (25 μg/mL) significantly (p < 0.01) reduced STZ-induced mitochondrial (51.24 %) and membrane (41.69 %) damage, as shown by MTT and LDH assays. BME markedly reduced intracellular ROS, protein carbonylation, and lipid peroxidation (p < 0.001), while restoring mitochondrial membrane potential, ATP levels, enzymatic antioxidant levels, and glutathione content. Furthermore, BME upregulated brain-derived neurotrophic factor (BDNF) expression and inhibited AGE formation. Collectively, these findings highlight the antioxidant, antiglycation, and neurotrophic actions of BME, underscoring its promise as a multi-targeted phytotherapeutic candidate for DN management.

糖尿病神经病变（DN）是糖尿病的主要并发症，其特征是由高血糖诱导的氧化应激、线粒体功能障碍和晚期糖基化终产物（AGE）积累驱动的进行性神经元损伤。马齿苋（Bacopa monniera）富含神经活性皂苷马齿苋苷A (Bacoside A， BA)，具有神经保护作用。本研究探讨了monniera提取物（BME）抗STZ诱导的SH-SY5Y神经母细胞瘤细胞毒性的分子机制。计算机ADMET分析显示，BA及其皂苷元具有良好的药代动力学特征，包括增强吸收、降低毒性和提高清除率，支持其在BME中的生物活性作用。BME预处理（25 μg/mL）显著(p

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引用次数: 0

Thymoquinone attenuates poly(I:C)-induced cellular stress via PKR/ATF4/CHOP signaling and autophagy modulation in human alveolar epithelial cells 百里醌通过PKR/ATF4/CHOP信号传导和自噬调节，减弱人肺泡上皮细胞poly（I:C）诱导的细胞应激。

IF 2.7 3区医学 Q3 TOXICOLOGY

Toxicology in Vitro

Pub Date : 2025-10-12 DOI: 10.1016/j.tiv.2025.106165

Umut Kerem Kolac , Bakiye Goker Bagca , Gizem Donmez Yalcin , Mina Ilayda Taskiran , Soner Sertan Kara

Alveolar type II (ATII) epithelial cells are essential for maintaining pulmonary homeostasis and defending against viral pathogens. Polyinosinic:polycytidylic acid [Poly(I:C)], a synthetic analog of viral double-stranded RNA, activates protein kinase R (PKR)-mediated stress responses in these cells. Thymoquinone, the principal bioactive compound of Nigella sativa, exhibits antioxidant and immunomodulatory properties; however, its regulatory effects on viral mimic-induced stress pathways in alveolar epithelium are not well defined. In this study, primary human ATII cells were treated with Poly(I:C), thymoquinone, or their combination for 24 h. Activation of the PKR/eIF2α/ATF4/CHOP integrated stress response axis and apoptotic gene expression was evaluated. Autophagic activity was assessed by monitoring LC3-II/I, p62, and BECLIN1 expression levels, supported by fluorescence microscopy and flow cytometry. Intracellular reactive oxygen species (ROS) levels were quantified using a probe-based flow cytometric assay. Poly(I:C) activated the PKR/eIF2α/ATF4/CHOP pathway and increased the BAX/BCL2 ratio, indicating enhanced cellular stress and apoptosis. Thymoquinone co-treatment attenuated these effects. While Poly(I:C) enhanced autophagic flux, evidenced by increased LC3-II/LC3-I ratio and BECLIN1 expression with decreased p62, thymoquinone reversed these alterations, suggesting suppressed autophagy. Imaging and flow cytometry confirmed that thymoquinone led to autophagosome accumulation, implying impaired autophagic clearance. Additionally, thymoquinone significantly reduced Poly(I:C)-induced intracellular ROS production. These findings demonstrate the cytoprotective potential of thymoquinone via modulation of stress signaling, autophagy, and oxidative stress in alveolar epithelial cells.

肺泡II型（ATII）上皮细胞对维持肺稳态和防御病毒病原体至关重要。polyinosic:polycytidylic acid [Poly(I:C)]是一种合成的病毒双链RNA类似物，可激活这些细胞中蛋白激酶R （PKR）介导的应激反应。百里醌是黑草的主要生物活性化合物，具有抗氧化和免疫调节作用；然而，其对肺泡上皮中病毒模拟诱导的应激通路的调节作用尚不明确。在这项研究中，用Poly（I:C）、百里醌或它们的组合处理人ATII原代细胞24 h。评估PKR/eIF2α/ATF4/CHOP综合应激反应轴的激活和凋亡基因的表达。在荧光显微镜和流式细胞术的支持下，通过监测LC3-II/I、p62和BECLIN1的表达水平来评估自噬活性。细胞内活性氧（ROS）水平使用基于探针的流式细胞术测定定量。Poly（I:C）激活PKR/eIF2α/ATF4/CHOP通路，增加BAX/BCL2比值，表明细胞应激和凋亡增强。百里醌联合治疗减弱了这些作用。聚（I:C）增强了自噬通量，LC3-II/LC3-I比值增加，BECLIN1表达增加，p62降低，百里醌逆转了这些改变，提示自噬受到抑制。成像和流式细胞术证实，百里醌导致自噬体积聚，这意味着自噬清除受损。此外，百里醌显著减少Poly（I:C）诱导的细胞内ROS的产生。这些发现表明，百里醌通过调节肺泡上皮细胞的应激信号、自噬和氧化应激，具有细胞保护潜力。

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引用次数: 0

Metabolic stability and effects of microsomal enzymes on the activity of the sonic hedgehog pathway inhibitor piperonyl butoxide 代谢稳定性和微粒体酶对超音hedgehog途径抑制剂胡椒酰丁醇活性的影响。

IF 2.7 3区医学 Q3 TOXICOLOGY

Toxicology in Vitro

Pub Date : 2025-10-07 DOI: 10.1016/j.tiv.2025.106156

Kenneth S. Rivera-González , Cameron O. Scarlett , Robert J. Lipinski

The pesticide synergist piperonyl butoxide (PBO) is a methylenedioxy compound used in many pesticide formulations. Previous studies identified PBO as an inhibitor of the Sonic hedgehog (Shh) signaling pathway and linked prenatal PBO exposure to adverse developmental outcomes. Mixed-function oxidases have been proposed to metabolize PBO, but the specific enzymes involved in its depletion have not been identified. Here we examined the metabolic stability of PBO in the presence of human liver microsomes and the involvement of the CYP-450 (CYPs) and FMO enzyme families on the in vitro depletion of PBO. We found that PBO is readily depleted by microsomal enzymes in the presence of NADPH. The CYP inhibitor SKF-525 A significantly decreased PBO depletion, while the FMO inhibitor methimazole did not. We then examined the depletion capacity of individual CYPs, focusing on isoforms with common human polymorphisms. CYP2C19, CYP2C9, and CYP3A4 exhibited the greatest PBO depletion capacity, while CYP1A2 and CYP2D6 demonstrated moderate capacity. Finally, the effect of microsomal activity on the antagonist activity of PBO against the Sonic hedgehog (Shh) pathway was assessed. Microsomal depletion reduced but did not eliminate the antagonistic activity of PBO on Shh pathway signaling activity. Collectively, these findings suggest a major role for mixed-function oxidases in PBO depletion and indicate the possible involvement of specific CYP isoforms.

农药增效剂胡椒酰丁醇（PBO）是一种用于许多农药配方的亚甲二氧基化合物。先前的研究发现PBO是Sonic hedgehog （Shh）信号通路的抑制剂，并将产前PBO暴露与不良发育结果联系起来。混合功能氧化酶已被提出代谢PBO，但具体的酶参与其消耗尚未确定。在这里，我们研究了PBO在人肝微粒体存在下的代谢稳定性，以及cyp450 （CYPs）和FMO酶家族在PBO体外消耗中的作用。我们发现在NADPH存在的情况下PBO很容易被微粒体酶耗尽。CYP抑制剂SKF-525 A显著降低PBO耗损，而FMO抑制剂甲巯咪唑则没有。然后，我们检查了单个CYPs的消耗能力，重点关注具有常见人类多态性的同种异构体。CYP2C19、CYP2C9和CYP3A4具有最大的PBO消耗能力，CYP1A2和CYP2D6具有中等的PBO消耗能力。最后，我们评估了微粒体活性对PBO对Sonic hedgehog （Shh）通路拮抗剂活性的影响。微粒体缺失降低但不消除PBO对Shh通路信号活性的拮抗活性。总的来说，这些发现表明混合功能氧化酶在PBO消耗中的主要作用，并表明特定CYP异构体可能参与其中。

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引用次数: 0

Liposomal nanoparticles containing adenosine triphosphate targeted by heart-specific peptide ligands as antidotes for aluminum phosphide poisoning in isolated rat cardiomyocyte cell line 心脏特异性肽配体靶向三磷酸腺苷纳米粒脂质体作为离体大鼠心肌细胞系磷化铝中毒的解毒剂。

IF 2.7 3区医学 Q3 TOXICOLOGY

Toxicology in Vitro

Pub Date : 2025-10-06 DOI: 10.1016/j.tiv.2025.106155

Roghayeh Jahani , Hamidreza Mohammadi , Mohammad Seyedabadi , Vajihe Alinezhad , Javad Akhtari

Aluminum phosphide (ALP) poisoning remains a critical challenge because of the limited number of treatment options. ALP disrupts the electron transport chain, causing ATP depletion, oxidative stress, and cytotoxicity. This study developed ischemic myocardium-targeting peptide (IMTP)-conjugated ATP-loaded liposomes (ATP-L) to mitigate ALP-induced cardiotoxicity. ATP-L was prepared via thin-film hydration and freeze–thaw methods, followed by peptide conjugation via maleimide-PEG₂₀₀₀-DSPE. Liposome characterization revealed average sizes of 134.8 nm (DLS) and 113 nm (TEM), zeta potential of +11.33 mV, PDI of 0.17, and ATP encapsulation efficiency of 41 %.

In this study, the rat cardiomyocyte cell line (H₉C₂) was used. In H₉C₂ cells, ALP exhibited dose-dependent toxicity, whereas ATP, non-targeted ATP-loaded liposomes (NT-ATP-L), and ATP-L showed no cytotoxicity. Co-treatment with ATP, NT-ATP-L, and ATP-L via ALP (18.27 μg/ml) for 3 h significantly reduced the levels of oxidative stress markers, restoring the cellular redox balance.

These findings highlight ATP-L as a promising antioxidant nanotherapy for treating ALP poisoning. ATP-L combats ALP-induced cardiotoxicity by restoring ATP and reducing oxidative damage. The use of IMTP ensures precise targeting to ischemic cardiac tissues, potentially improving efficacy and minimizing off-target effects. This strategy offers a novel approach to managing ALP toxicity. Further studies are needed to validate the in vivo results and optimize the formulation for clinical use. Overall, ATP-L represents a significant advancement in targeted nanomedicine for toxicological emergencies.

磷化铝（ALP）中毒仍然是一个重大挑战，因为有限的治疗方案。ALP破坏电子传递链，引起ATP耗竭、氧化应激和细胞毒性。本研究开发了缺血心肌靶向肽（IMTP）偶联atp负载脂质体（ATP-L）来减轻alp诱导的心脏毒性。通过薄膜水化和冻融法制备ATP-L，然后通过马来酰亚胺- peg2000 - dspe进行肽偶联。脂质体的平均粒径为134.8 nm （DLS）和113 nm (TEM)， zeta电位为+11.33 mV， PDI为0.17，ATP包封效率为41 %。本研究采用大鼠心肌细胞系（H9C2）。在H9C2细胞中，ALP表现出剂量依赖性毒性，而ATP、非靶向ATP负载脂质体（NT-ATP-L）和ATP-l则没有细胞毒性。通过ALP（18.27 μg/mL）与ATP、NT-ATP-L和ATP- l共处理3 h，可显著降低氧化应激标志物水平，恢复细胞氧化还原平衡。这些发现强调了ATP-L作为一种治疗ALP中毒的有前途的抗氧化剂纳米疗法。ATP- l通过恢复ATP和减少氧化损伤来对抗ATP诱导的心脏毒性。使用IMTP可确保精确靶向缺血心脏组织，潜在地提高疗效并最大限度地减少脱靶效应。该策略提供了一种管理ALP毒性的新方法。需要进一步的研究来验证体内结果并优化临床使用的配方。总的来说，ATP-L代表了针对毒理学紧急情况的靶向纳米医学的重大进步。

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引用次数: 0

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