Current Research in Toxicology最新文献

MicroRNA-mediated changes contributing to benzo[a]pyrene toxicity in a 3D respiratory model for asthma 在哮喘三维呼吸模型中，microrna介导的变化对苯并[a]芘毒性的影响

IF 2.9 Q2 TOXICOLOGY

Current Research in Toxicology

Pub Date : 2026-01-01 DOI: 10.1016/j.crtox.2026.100283

Reese M. Valdez , Yvonne Chang , Jamie M. Pennington , Susan C. Tilton

There is increased emphasis on understanding how non-chemical stressors that contribute to inflammation in the lung may influence adverse health outcomes after chemical exposures. Prior studies in an in vitro respiratory model of type 2 asthmatic inflammation found cells from the asthmatic phenotype respond uniquely to benzo[a]pyrene (BAP) treatment compared to normal cells across multiple endpoints related to mucus production, goblet cell hyperplasia, mucociliary dysfunction and airway remodeling. To further understand how cellular response to BAP is regulated in a model of inflammation-based disease, this study examines changes in miRNA and mRNA regulation following BAP exposure in primary human bronchial epithelial cells (HBECs) cultured at the air–liquid interface with normal and interlukin-13 (IL-13) induced asthmatic phenotypes. Primary 3D HBECs differentiated in the presence and absence of 10 ng/mL IL-13 were treated on day 25 with 158 µM BAP for 48 h. Differentially expressed (q < 0.01) miRNA and mRNA were analyzed to predict miRNA target interactions and assess the functional consequences of miRNAs in each phenotype. While BAP-treated HBEC with the IL-13 asthmatic phenotype had a similar number of differentially expressed miRNA (93 up- and 100 down-regulated) compared to BAP-treated normal HBEC (93 up- and 94 down-regulated), IL-13 HBEC treated with BAP were shown to have unique enrichment of miRNA targets involved in up-regulation of cell cycle processes and down-regulation of processes related to NOTCH, WNT, and Hedgehog signaling. These data are the first to provide insight into the role of miRNAs as regulators of chemical toxicity in a respiratory model of inflammation-based disease.

人们越来越重视了解导致肺部炎症的非化学应激源如何影响化学暴露后的不良健康结果。先前在2型哮喘性炎症的体外呼吸模型中研究发现，与正常细胞相比，哮喘表型细胞对苯并[a]芘（BAP）治疗的反应独特，涉及粘液产生、杯状细胞增生、粘膜纤毛功能障碍和气道重塑等多个终点。为了进一步了解细胞对BAP的反应在炎症性疾病模型中是如何调节的，本研究检测了在正常和白介素-13 （IL-13）诱导的哮喘表型的气液界面培养的原代人支气管上皮细胞（HBECs）暴露于BAP后miRNA和mRNA调节的变化。在存在和不存在10 ng/mL IL-13的情况下分化的原发性3D HBECs在第25天用158µM BAP处理48小时。分析差异表达（q < 0.01）的miRNA和mRNA，以预测miRNA靶相互作用并评估每种表型中miRNA的功能后果。与BAP处理的正常HBEC（93上调，94下调）相比，BAP处理的IL-13哮喘表型HBEC具有相似数量的差异表达miRNA（93上调，100下调），但BAP处理的IL-13 HBEC具有独特的富集miRNA靶标，涉及细胞周期过程的上调和NOTCH， WNT和Hedgehog信号传导相关过程的下调。这些数据首次提供了mirna在炎症性疾病呼吸模型中作为化学毒性调节因子的作用。

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引用次数: 0

Multigenerational effects of uranium exposure reveal stronger testicular dysregulation in the second generation 铀暴露的多代效应显示第二代睾丸失调更严重

IF 2.9 Q2 TOXICOLOGY

Current Research in Toxicology

Pub Date : 2026-01-01 DOI: 10.1016/j.crtox.2025.100279

Audrey Legendre , Céline Gloaguen , Dimitri Kereselidze , Nawel Saci , Sophia Murat El Houdigui , Pascal Froment , Christelle Elie , Catherine Defoort , Philippe Lestaevel , Mohamed Amine Benadjaoud , Maâmar Souidi , Stéphane Grison

Background

Infertility is a significant public health issue that can be influenced by environmental pollutants. As a radioactive heavy metal and environmental contaminant, uranium has the potential to impact fertility.

Objective

This study assesses the multigenerational reproductive effects of chronic, non-nephrotoxic uranium exposure across three generations of male rats.

Methods

In this study, a non-nephrotoxic uranium solution (40 mg/L) was chronically administered via drinking water to male and female F0 rats (n = 20 per group) throughout their lifespan. The objective was to evaluate the potential reprotoxic effects of uranium on males across three generations (F0, F1, F2), with a focus on spermatogenesis, steroidogenesis, and testicular homeostasis, including oxidative stress, inflammation, apoptosis, and vitamin D metabolism.

Results

Steroidogenesis was modulated in all generation, with dysregulation of sex and pituitary hormones (testosterone, estradiol, gonadotropins, Luteinizing Hormone (LH), Follicle-Stimulating Hormone (FSH). Morphological and histological changes in the testes were observed in both the F1 and F2 generations. Spermatogenesis was dysregulated by an increased proportion of seminiferous tubules at stage I-VI and reduced expression of TH2B and eppin mRNA. Interestingly, gene expression analysis of several markers involved in the regulation and protection of testicular homeostasis revealed significant effects only on the F2 generation. In this generation, uranium exposure also disrupted vitamin D metabolism in the testes.

Conclusion

Uranium may impair testicular function, with more pronounced effects observed in the F2 generation. These findings highlight its potential for multigenerational toxicity and underscore the need for further research into its impact on human reproductive health.

生育能力是一个重大的公共卫生问题，可能受到环境污染物的影响。作为一种放射性重金属和环境污染物，铀有可能影响生育能力。目的研究慢性无肾毒性铀暴露对三代雄性大鼠多代生殖的影响。方法采用无肾毒性的铀溶液（40 mg/L）长期灌胃，每组20只，终生灌胃。目的是评估铀对三代雄性（F0, F1, F2）的潜在生殖毒性影响，重点关注精子发生，类固醇发生和睾丸稳态，包括氧化应激，炎症，细胞凋亡和维生素D代谢。结果甾体生成在各代均受到调节，性激素和垂体激素（睾酮、雌二醇、促性腺激素、促黄体生成素（LH）、促卵泡激素（FSH））调节异常。在F1代和F2代均观察到睾丸的形态和组织学变化。在I-VI期，精管比例增加，TH2B和eppin mRNA表达减少，导致精子发生失调。有趣的是，对几个参与睾丸稳态调节和保护的标记的基因表达分析显示，仅在F2代上有显著影响。在这一代人中，铀暴露也破坏了睾丸中维生素D的代谢。结论铀可损害睾丸功能，对F2代的影响更为明显。这些发现强调了其可能具有多代毒性，并强调需要进一步研究其对人类生殖健康的影响。

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引用次数: 0

Scoparone induces mitophagy and apoptosis via ROS accumulation in pancreatic cancer cells Scoparone通过ROS积累诱导胰腺癌细胞自噬和凋亡

IF 2.9 Q2 TOXICOLOGY

Current Research in Toxicology

Pub Date : 2026-01-01 DOI: 10.1016/j.crtox.2026.100281

Ningna Weng , Luping Lin , Tong Lin , Jinlu Liu , Kai Zhu , Sha Huang

Pancreatic cancer (PC) is one of the deadliest malignancies worldwide. In the present study, we demonstrated that a traditional Chinese medicine extract monomer, scoparone (Scop), significantly inhibited the growth of PC cells both in vitro and in vivo. Further studies revealed that Scop could induce PINK1/Parkin-mediated mitophagy and apoptosis in PC cells; thus, inhibition of mitophagy could alleviate the anti-PC effect and apoptosis of Scop. Mechanistically, Scop exerts its anti-PC effects via the Akt/mTOR pathway. In addition, Scop increases the level of cellular reactive oxygen species (ROS) in PC cells, which may be a key factor, as the ROS inhibitor N-acetylcysteine significantly reversed the effects of mitophagy and apoptosis in PC cells. Our findings highlight Scop shows potential as a therapeutic lead candidate, offering novel insights into the antitumor potential of traditional Chinese medicine. This study elucidates the critical role of Scop in regulating mitophagy and apoptosis in PC cells, providing a foundation for future therapeutic development.

胰腺癌是世界上最致命的恶性肿瘤之一。在本研究中，我们证明了一种中药提取物单体，scoparone (Scop)，在体外和体内都能显著抑制PC细胞的生长。进一步研究发现，scopp可诱导PINK1/ parkinson介导的PC细胞有丝分裂和凋亡；因此，抑制线粒体自噬可以减轻Scop的抗pc作用和细胞凋亡。从机制上讲，scopp通过Akt/mTOR途径发挥其抗pc作用。此外，scopp增加了PC细胞中的细胞活性氧（ROS）水平，这可能是一个关键因素，因为ROS抑制剂n -乙酰半胱氨酸显著逆转了PC细胞的线粒体自噬和凋亡作用。我们的研究结果突出了Scop作为一种潜在的治疗候选药物，为传统中药的抗肿瘤潜力提供了新的见解。本研究阐明了scopp在调节PC细胞有丝分裂和凋亡中的重要作用，为今后的治疗开发奠定了基础。

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引用次数: 0

Identifying androgen receptor antagonists using a metabolically competent high-throughput screening assay 鉴定雄激素受体拮抗剂使用代谢能力高通量筛选试验

IF 2.9 Q2 TOXICOLOGY

Current Research in Toxicology

Pub Date : 2026-01-01 DOI: 10.1016/j.crtox.2025.100278

Caitlin Lynch, Pranav Shah, Jinghua Zhao, Xin Xu, Ruili Huang, Menghang Xia

Androgen receptor (AR) is a nuclear receptor with a well-established role in sexual function and development. Modifications in AR can lead to endocrine disruption, cancer, and other diseases, making it imperative to identify compounds that influence these changes. AR modulators have been identified using immortalized cell lines in a high-throughput screening assay. However, most of these methods do not incorporate metabolism, leading to misclassification of compounds that normally require it to become AR modulators. Metabolism transforms exogenous parent compounds into metabolites that are easier to excrete, and normally less active than the parent. However, some metabolites modulate AR more effectively than the parent compound. Incorporating metabolism into a large compound screen can identify active metabolites as potential AR modulators. In this study, we optimized a high-throughput screening assay that included rat liver microsomes (RLM) as an exogenous metabolic system to detect AR antagonists. A robotic screen of the LOPAC library + 88 Tox21 compounds (a total of 1365 unique compounds) was then performed to validate the assay and identify any bioactivated AR modulators within the test library. Fifty-five compounds were identified as potential AR antagonists; 9 compounds out of these 55 compounds were found to have significant potency shifts between RLM free and RLM assays, suggesting the necessity of metabolism for their AR activity. A concurrent assay using heat-inactivated RLM was conducted to discern the true activity of each compound. Metabolic stability assays were also performed on the top compounds to clarify their ability to transition from parent to metabolite using RLM. Four compounds were identified as novel parent compounds requiring metabolism to become more potent AR antagonists. However, only 4,5-dianilinophthalimide (DAPH) displayed a clear concentration–response curve with a more potent IC₅₀ when RLM was included compared to its parallel screens, identifying it as a true AR antagonist requiring metabolism.

雄激素受体（AR）是一种核受体，在性功能和发育中起着重要作用。AR的改变可导致内分泌紊乱、癌症和其他疾病，因此必须确定影响这些变化的化合物。在高通量筛选试验中，使用永生化细胞系鉴定了AR调节剂。然而，这些方法中的大多数没有纳入代谢，导致通常需要它成为AR调节剂的化合物的错误分类。代谢将外源母体化合物转化为更容易排泄的代谢物，通常比母体活性低。然而，一些代谢物比母体化合物更有效地调节AR。将代谢纳入一个大的复合屏幕可以识别活性代谢物作为潜在的AR调节剂。在本研究中，我们优化了一种高通量筛选方法，该方法将大鼠肝微粒体（RLM）作为外源性代谢系统来检测AR拮抗剂。然后对LOPAC文库+ 88种Tox21化合物（共1365种独特化合物）进行机器人筛选，以验证该分析并在测试文库中识别任何生物活性AR调节剂。55种化合物被鉴定为潜在的AR拮抗剂；在55种化合物中，有9种化合物在RLM游离和RLM检测中有显著的效价变化，这表明它们的AR活性与代谢有关。同时使用热灭活RLM进行测定，以辨别每种化合物的真实活性。利用RLM对顶级化合物进行了代谢稳定性分析，以阐明它们从母体转化为代谢物的能力。四种化合物被确定为新的母体化合物，需要代谢才能成为更有效的AR拮抗剂。然而，只有4,5-二苯酞酰亚胺（DAPH）显示出清晰的浓度-反应曲线，与平行筛选相比，当RLM纳入时，其IC50更有效，这表明它是一种真正需要代谢的AR拮抗剂。

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引用次数: 0

Zearalenone exposure may increase the risk of non-alcoholic fatty liver disease by activating CYP1B1-SCD1 玉米赤霉烯酮暴露可能通过激活CYP1B1-SCD1增加非酒精性脂肪性肝病的风险

IF 2.9 Q2 TOXICOLOGY

Current Research in Toxicology

Pub Date : 2025-12-13 DOI: 10.1016/j.crtox.2025.100277

Haonan Ruan , Jing Zhang , Yunyun Wang , Dan Zhang , Jiaoyang Luo , Meihua Yang

Zearalenone (ZEN) is an oestrogen-like mycotoxin that widely contaminates food and feed worldwide. Current research suggests that ZEN causes liver injury by disrupting hepatic lipid metabolism. Furthermore, prolonged disturbances in hepatic lipid metabolism are believed to play a role in the progression of non-alcoholic fatty liver disease (NAFLD). However, the exact association between ZEN exposure and the development of NAFLD is unclear. In this study, we established a rat model of ZEN-induced hepatic lipid accumulation (2.5, 5, 10 mg/kg/d b.w.,14 d, i.g.) to investigate the key targets of ZEN-induced hepatic lipid accumulation and to explore the potential link between ZEN exposure and NAFLD. Histological staining of rat liver showed that ZEN caused significant pathological changes and lipid accumulation; biochemical analysis showed that ZEN significantly and dose-dependently increased serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and disrupted the serum lipid profile in rats; proteomic analysis showed that ZEN significantly altered protein expression levels in rat liver, especially SOAT1, SOAT2, CYP1B1 and SCD1 (p < 0.05). Through bioinformatics analyses, we combined ZEN exposure with a database of NAFLD clinical samples to reveal that ZEN exposure may increase the risk of NAFLD through activation of the CYP1B1-SCD1 pathway, and further animal experiments confirmed this. This study identifies the key target of ZEN-induced lipid accumulation and provides a basis for further research on the intrinsic link between ZEN exposure and NAFLD.

玉米赤霉烯酮（ZEN）是一种雌激素样真菌毒素，广泛污染世界各地的食品和饲料。目前的研究表明，ZEN通过破坏肝脏脂质代谢导致肝损伤。此外，肝脂质代谢的长期紊乱被认为在非酒精性脂肪性肝病（NAFLD）的进展中起作用。然而，ZEN暴露与NAFLD发展之间的确切联系尚不清楚。在本研究中，我们建立了禅宗诱导的大鼠肝脏脂质积累模型（2.5,5,10 mg/kg/d b.w.,14 d, ig），以研究禅宗诱导的肝脏脂质积累的关键靶点，并探讨禅宗暴露与NAFLD之间的潜在联系。大鼠肝脏组织学染色显示，ZEN引起了明显的病理改变和脂质堆积；生化分析显示，ZEN显著且剂量依赖地提高了大鼠血清中谷草转氨酶（AST）和丙氨酸转氨酶（ALT）水平，并破坏了血脂谱；蛋白质组学分析显示，ZEN显著改变了大鼠肝脏蛋白表达水平，尤其是SOAT1、SOAT2、CYP1B1和SCD1 （p < 0.05）。通过生物信息学分析，我们将ZEN暴露与NAFLD临床样本数据库相结合，发现ZEN暴露可能通过激活CYP1B1-SCD1通路而增加NAFLD的风险，进一步的动物实验也证实了这一点。本研究确定了ZEN诱导脂质积累的关键靶点，为进一步研究ZEN暴露与NAFLD之间的内在联系提供了基础。

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引用次数: 0

Application to developmental toxicity testing of a novel method for whole-brain imaging of microglia in zebrafish 斑马鱼小胶质细胞全脑成像新方法在发育毒性试验中的应用

IF 2.9 Q2 TOXICOLOGY

Current Research in Toxicology

Pub Date : 2025-12-11 DOI: 10.1016/j.crtox.2025.100276

Mizuki Yuge , Junko Koiwa , Takashi Shiromizu , Eri Wakai , Akira Migoguchi , Yuhei Nishimura

Microglia, parenchymal macrophages resident in the central nervous system, regulate brain development by dynamically changing their functional and morphological states in a spatiotemporal-dependent manner. Because the function of microglia may differ depending on their location, their status should ideally be assessed within discrete brain regions. In this study, we developed a novel whole-brain imaging method to visualize microglial morphology in the forebrain, midbrain, and hindbrain of live zebrafish larvae at 5–6days post-fertilization, and quantified various morphological parameters using MorphoLibJ, a publicly available tool for mathematical analysis of three-dimensional images. We applied this method to assess the developmental toxicity of ethanol and valproic acid on microglial morphology in the zebrafish larvae, and were able to detect marked differences in the spatiotemporal effects of each compound. The duration of exposure required to detect significant changes in microglial morphology was shorter for ethanol than for valproic acid, and microglia in the forebrain diencephalon region were more susceptible to toxicity induced by ethanol compared with valproic acid. These results suggest that our whole-brain microglial imaging and modeling method may be a versatile tool to assess the developmental toxicity of chemicals in zebrafish.

小胶质细胞是中枢神经系统的巨噬细胞，通过动态改变其功能和形态状态，以时空依赖的方式调节大脑发育。由于小胶质细胞的功能可能因其位置而异，因此它们的状态最好是在独立的大脑区域内进行评估。在这项研究中，我们开发了一种新的全脑成像方法来可视化受精后5 - 6天活斑马鱼幼虫前脑、中脑和后脑的小胶质细胞形态，并使用MorphoLibJ（一个公开的三维图像数学分析工具）对各种形态学参数进行量化。我们应用该方法评估了乙醇和丙戊酸对斑马鱼幼体小胶质细胞形态的发育毒性，并能够检测到每种化合物在时空效应上的显著差异。与丙戊酸相比，乙醇暴露所需的时间短于丙戊酸，前脑间脑区域的小胶质细胞对乙醇诱导的毒性更敏感。这些结果表明，我们的全脑小胶质成像和建模方法可能是评估化学物质对斑马鱼发育毒性的通用工具。

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引用次数: 0

Association of serotonin and ergot alkaloids on tissue partitioning and contractile response of bovine blood vessels 血清素和麦角生物碱对牛血管组织分配和收缩反应的影响

IF 2.9 Q2 TOXICOLOGY

Current Research in Toxicology

Pub Date : 2025-12-03 DOI: 10.1016/j.crtox.2025.100272

Eriton E.L. Valente , David L. Harmon , John May , Huihua Ji , Ronald J. Trotta , James L. Klotz

Ergot alkaloids can bind serotonin (5-HT) receptors interfering with many physiological functions. However, the mechanism has not been completely established. The objective was to evaluate whether the association of 5-HT and the ergot alkaloid, ergovaline, in a 24-h pre-incubation can affect vascular tissue partitioning and contractile responses. Cross-sections of saphenous veins from five steers were used. In the tissue partitioning experiment, the treatments were the combination of three levels of ergovaline (2.01 × 10⁻⁸ M, 2.01 × 10⁻⁷ M and 2.01 × 10⁻⁶ M) with three levels of 5-HT and a control (5 × 10⁻⁸ M, 5 × 10⁻⁷ M, 5 × 10⁻⁶ M and 0 M). After 24-h exposure to the treatments, the blood vessels were washed. Afterward, the tissues were analyzed for ergovaline and 5-HT concentrations. For the contractility experiment, a parallel set of blood vessels was evaluated in the myograph after 24-h pre-incubation with the respective treatments: 1) no additional compound; 2) tall fescue seed extract (2.01 × 10⁻⁷ M of ergovaline); 3) serotonin (5 × 10⁻⁷ M); or 4) ERV plus 5-HT. The tissue ergovaline increased (P < 0.001) about 27.5-fold when the concentration in the media increased 100-fold (2.01 × 10⁻⁸ M to 2.01 × 10⁻⁶ M). However, the presence of 5-HT did not affect (P = 0.368) tissue ergovaline partitioning. When 5-HT was not added, ergovaline reduced (P < 0.05) the 5-HT concentration in the blood vessel. Pre-incubation with ergovaline reduced contractile response by about 95 % (P < 0.05) and 5-HT did not change its effect. Ergot alkaloid partitioning is associated with reduced tissue 5-HT levels and blood vessel contractility.

麦角生物碱能结合血清素（5-HT）受体，干扰多种生理功能。然而，这一机制尚未完全建立。目的是评估5-羟色胺和麦角生物碱麦角缬氨酸在24小时孵育前是否会影响血管组织分配和收缩反应。采用5头牛的隐静脉横切面。组织分割实验,处理的结合三个级别的ergovaline(2.01 × 10−8米,2.01 × 10−7 M和2.01 × 10−6米)与5 -三个层次和控制(5 × 10−8 M, 5 × 10−7米,5 × 10−6 M和0 M)。处理24小时后，清洗血管。随后，对组织进行麦角缬氨酸和5-羟色胺浓度分析。在收缩性实验中，分别在预处理24小时后，在肌图上评估一组平行血管：1)不添加任何化合物；2)高羊茅籽提取物（2.01 × 10−7 M麦角缬氨酸）；3)血清素（5 × 10−7 M）；或4)ERV + 5-HT。当培养基中麦角碱浓度增加100倍（2.01 × 10−8 M至2.01 × 10−6 M）时，组织麦角碱增加约27.5倍（P < 0.001）。然而，5-HT的存在不影响组织麦角氨酸分配（P = 0.368）。不添加5-HT时，麦角缬氨酸降低了血管中5-HT的浓度（P < 0.05）。麦角缬氨酸预孵育可使收缩反应降低约95% % (P < 0.05)，而5-HT未改变其作用。麦角生物碱分配与降低组织5-羟色胺水平和血管收缩性有关。

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引用次数: 0

Ca2+-independent cytotoxicity of menthol in the A549 lung cancer cell line 薄荷醇对A549肺癌细胞系Ca2+非依赖性细胞毒性的影响

IF 2.9 Q2 TOXICOLOGY

Current Research in Toxicology

Pub Date : 2025-11-30 DOI: 10.1016/j.crtox.2025.100271

Kenji Takahashi, Toshio Ohta

Menthol evokes cooling sensations by activating the transient receptor potential melastatin 8 (TRPM8) channel, resulting in relaxing, anti-inflammatory, and analgesic effects when administered through inhalation and topical application. Although the toxicity of menthol is relatively low, the mechanism underlying menthol-induced cytotoxic effects remains unclear. Thus, this study aimed to investigate the cytotoxic effects of menthol in the A549 lung cancer cell line. Menthol induced increases in intracellular Ca²⁺ concentrations ([Ca²⁺]_i) in distinct modes depending on its concentration. A relatively low concentration (0.3 mM) of menthol activated transient receptor potential ankyrin 1 (TRPA1) despite the expression of TRPM8 in A549 cells. A higher concentration (3 mM) of menthol nonspecifically induced Ca²⁺ release from intracellular stores. Menthol inhibited Ca²⁺-ATPase in the organelle membrane. At 3 mM, menthol elicited necrotic cell death accompanied by morphological changes within 60 min. This cytotoxicity was not prevented by HC-030031 (a TRPA1 blocker) or BAPTA-AM (an intracellular Ca²⁺ chelator). Furthermore, the analysis of the cytotoxicity of monoterpene analogs of menthol revealed structure-related activity in menthol-induced cytotoxicity. These findings indicate that menthol-induced cytotoxic effects are concentration-dependent and may provide valuable insights into novel therapeutic strategies for lung cancer.

薄荷醇通过激活瞬时受体电位美拉他汀8 （TRPM8）通道来唤起凉爽的感觉，通过吸入和局部应用产生放松，抗炎和镇痛作用。虽然薄荷醇的毒性相对较低，但其诱导细胞毒性作用的机制尚不清楚。因此，本研究旨在探讨薄荷醇对A549肺癌细胞系的细胞毒性作用。薄荷醇诱导细胞内Ca2+浓度（[Ca2+]i）以不同的模式增加，这取决于它的浓度。尽管在A549细胞中表达TRPM8，但相对低浓度（0.3 mM）的薄荷醇激活了瞬时受体电位锚蛋白1 （TRPA1）。较高浓度（3mm）的薄荷醇非特异性诱导Ca2+从细胞内储存释放。薄荷醇抑制细胞器膜Ca2+- atp酶。在3mm时，薄荷醇在60min内引起坏死细胞死亡并伴有形态学改变。HC-030031 （TRPA1阻滞剂）或BAPTA-AM（细胞内Ca2+螯合剂）不能阻止这种细胞毒性。此外，对薄荷醇单萜类似物的细胞毒性分析揭示了薄荷醇诱导的细胞毒性与结构相关的活性。这些发现表明薄荷醇诱导的细胞毒性作用是浓度依赖性的，可能为肺癌的新治疗策略提供有价值的见解。

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引用次数: 0

Systematic evaluation of the evidence base on ethyl tert-butyl ether and tert-butyl alcohol for carcinogenic potential in humans; lack of concern based on animal cancer studies and mechanistic data 乙基叔丁基醚和叔丁基醇对人体致癌潜力证据的系统评价缺乏基于动物癌症研究和机制数据的关注

IF 2.9 Q2 TOXICOLOGY

Current Research in Toxicology

Pub Date : 2025-11-10 DOI: 10.1016/j.crtox.2025.100270

Brianna N. Rivera , Isabel A. Lea , Seneca Fitch , Neepa Choksi , Allison Franzen , James Bus , Erik Rushton , Susan J. Borghoff

Ethyl tert-butyl ether (ETBE), a fuel additive, and tert-butyl alcohol (TBA), a solvent and metabolite of ETBE and methyl tert-butyl ether (MTBE), may be encountered via inhalation, oral, or dermal exposure. This assessment evaluated the human carcinogenic hazard of ETBE and TBA by systematically reviewing available human, animal, and mechanistic data. No epidemiological studies were identified, and two standard cancer bioassays were available for each compound. Tumor responses were limited to low incidences at high exposure levels: liver tumors in male F344 rats, kidney tumors in male F344 rats, and thyroid tumors in female B6C3F1 mice exposed to ETBE or TBA, respectively. Mechanistic evidence was organized within the framework of the key characteristics of carcinogens (KCC) and established rodent non-genotoxic modes of action (MoAs) for the overall evaluation. Aside from supportive evidence for KCC2 (is genotoxic) and KCC10 (alters cell proliferation, death, or nutrient supply), mechanistic data across KCCs were sparse and inconsistent. Both substances lacked genotoxic activity with available data supporting non-genotoxic MoAs that are not relevant to humans. Overall, the evidence indicates little concern for a carcinogenic hazard of ETBE or TBA in humans.

乙基叔丁基醚（ETBE）是一种燃料添加剂，叔丁基醇（TBA）是ETBE和甲基叔丁基醚（MTBE）的溶剂和代谢物，可通过吸入、口服或皮肤接触接触到。本评估通过系统地回顾现有的人类、动物和机制数据，评估了ETBE和TBA对人类的致癌危害。没有发现流行病学研究，每种化合物都有两种标准的癌症生物测定方法。肿瘤反应仅限于高暴露水平下的低发生率：分别暴露于ETBE或TBA的雄性F344大鼠的肝脏肿瘤，雄性F344大鼠的肾脏肿瘤和雌性B6C3F1小鼠的甲状腺肿瘤。在致癌物关键特征（KCC）框架内组织机理证据，建立啮齿类动物非基因毒性作用模式（MoAs）进行总体评价。除了支持KCC2（基因毒性）和KCC10（改变细胞增殖、死亡或营养供应）的证据外，关于KCC2的机制数据很少且不一致。这两种物质都缺乏基因毒性活性，现有数据支持与人类无关的非基因毒性moa。总的来说，证据表明ETBE或TBA对人类的致癌危害很小。

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Microplastics and nanoplastics in the ocular environment: Pathways, toxic effects, and future challenges. 眼环境中的微塑料和纳米塑料：途径、毒性效应和未来挑战。

IF 2.9 Q2 TOXICOLOGY

Current Research in Toxicology

Pub Date : 2025-08-07 eCollection Date: 2025-01-01 DOI: 10.1016/j.crtox.2025.100251

Xiaotong Yu, Na Zhou, Qun Gao, Willie J G M Peijnenburg, Kun Yin, Lianzhen Li, Ye Wang

Micro- and Nanoplastics (MNPs) have emerged as a significant environmental concern due to their widespread distribution and potential toxicity. While extensive research has explored the impacts of MNPs on various human organs, the eye, a particularly vulnerable tissue, has been relatively neglected. This review systematically examines the potential pathways through which MNPs can enter the eye, their accumulation in ocular tissues, and their potential toxic effects. We discuss the mechanisms by which MNPs may disrupt ocular health, including their ability to induce oxidative stress and inflammation, promote apoptosis, and cause genotoxicity and neurotoxicity. Additionally, we highlight the importance of future research on the effects of MNPs on the visual system, addressing current limitations and suggesting potential research directions. By enhancing our understanding of the risks posed by MNPs to ocular health, we can develop effective strategies to protect human vision and safeguard public health.

微纳米塑料（MNPs）由于其广泛的分布和潜在的毒性已经成为一个重要的环境问题。虽然大量的研究已经探讨了MNPs对人体各种器官的影响，但眼睛这个特别脆弱的组织却相对被忽视了。这篇综述系统地研究了MNPs进入眼睛的潜在途径、它们在眼组织中的积累以及它们潜在的毒性作用。我们讨论了MNPs可能破坏眼健康的机制，包括它们诱导氧化应激和炎症、促进细胞凋亡以及引起遗传毒性和神经毒性的能力。此外，我们强调了未来研究MNPs对视觉系统影响的重要性，解决了当前的局限性并提出了潜在的研究方向。通过加强我们对MNPs对眼健康构成的风险的了解，我们可以制定有效的战略来保护人类视力和保障公众健康。

引用次数: 0