Toxicology最新文献_第7页

Role of the ROS/NLRP3/caspase-1 pathway in NiSO4-induced cellular pyroptosis and apoptosis in H9c2 cells ROS/NLRP3/caspase-1途径在NiSO4诱导的H9c2细胞热解和凋亡中的作用

IF 4.8 3区医学 Q1 PHARMACOLOGY & PHARMACY

Toxicology

Pub Date : 2024-11-06 DOI: 10.1016/j.tox.2024.153989

Xinrui Zhao , Yuxian Yun , Danni Zhou , Yuanyuan Ma , Xianfeng Luo , Benzhong Zhang

According to comprehensive research, the cardiovascular system is damaged by nickel exposure. The present study selected rat cardiomyocytes (H9c2 cells) and subjected them to varying doses of sodium nickel sulfate (NiSO₄) for 24 hours to better understand the mechanism of cardiovascular damage caused by NiSO₄ exposure. The relevant indicators were detected employing biochemical analysis, real-time quantitative polymerase chain reaction (RT-qPCR), and western blot, and flow cytometry was used to detect the cell apoptosis rate. The study revealed that the survival rate of H9c2 cells fell significantly when the concentration of NiSO₄ exposure rose. Moreover, it caused oxidative stress in H9c2 cells by raising the expression of reactive oxygen species and the concentration of LDH in the cell supernatants. After NiSO₄ exposure, the levels of ASC, NLRP3, gasdermin D, and caspase-1 in H9c2 cells increased, suggesting that H9c2 cells underwent pyroptosis induced by NiSO₄. In addition, NiSO₄ exposure also led to inflammation, with increased levels of interleukin [IL]-18, IL-1β. After adding the antioxidant N-Acetyl-L-cysteine (NAC), the level of ROS indicated that the oxidative stress level in H9c2 cells was reduced, western blot inhibited inflammation, the level of pyroptosis was reduced, and the activity of the NLRP3/caspase1 signaling pathway was reduced. To examine the connection between pyroptosis and apoptosis, the cells were treated with the caspase1 inhibitor Z-YVAD-Fluoromethyl Ketone (Z-YVAD-FMK, YVAD), which resulted in a significant decrease in the rate of cell apoptosis as well as a reduction in the activity of the related protein in the signaling pathway, which in turn decreased the level of pyroptosis. NiSO₄ could induce pyroptosis in H9c2 cells through the ROS/NLRP3/caspase-1 axis. Furthermore, NiSO₄-induced apoptosis and pyroptosis were found to be reduced by the addition of the caspase-1 inhibitor.

综合研究表明，镍暴露会损害心血管系统。本研究选取大鼠心肌细胞（H9c2 细胞），将其置于不同剂量的硫酸镍钠（NiSO4）中 24 小时，以更好地了解 NiSO4 暴露对心血管的损伤机制。研究采用生化分析、实时定量聚合酶链反应（RT-qPCR）和免疫印迹法检测相关指标，并用流式细胞术检测细胞凋亡率。研究发现，NiSO4 暴露浓度升高时，H9c2 细胞的存活率显著下降。此外，NiSO4 还能提高细胞上清液中活性氧的表达和 LDH 的浓度，从而引起 H9c2 细胞的氧化应激。暴露于NiSO4后，H9c2细胞中ASC、NLRP3、gasdermin D和caspase-1的水平升高，这表明H9c2细胞在NiSO4的诱导下发生了热变态反应。此外，暴露于NiSO4还会导致炎症，白细胞介素[IL]-18、IL-1β水平升高。加入抗氧化剂N-乙酰-L-半胱氨酸（NAC）后，ROS水平表明H9c2细胞的氧化应激水平降低，Western blot抑制了炎症，降低了热蛋白沉积水平，并降低了NLRP3/caspase1信号通路的活性。为了研究热凋亡与细胞凋亡之间的联系，用caspase1抑制剂Z-YVAD-Fluoromethyl Ketone（Z-YVAD-FMK，YVAD）处理细胞，结果发现细胞凋亡率显著降低，信号通路中相关蛋白的活性也降低，进而降低了热凋亡水平。NiSO4可通过ROS/NLRP3/caspase-1轴诱导H9c2细胞的热凋亡。此外，加入caspase-1抑制剂后，NiSO4诱导的细胞凋亡和热凋亡也会减少。

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引用次数: 0

Investigation of a broad diversity of nanoparticles, including their processes, as well as toxicity testing in diverse organs and systems 研究各种纳米粒子，包括其加工过程，以及在不同器官和系统中的毒性测试。

IF 4.8 3区医学 Q1 PHARMACOLOGY & PHARMACY

Toxicology

Pub Date : 2024-11-06 DOI: 10.1016/j.tox.2024.153985

Azhar U. Khan , Mohammad Qutob , Amel Gacem , Mohd. Rafatullah , Krishna Kumar Yadav , Pankaj Kumar , Javed Khan Bhutto , Meenal Rehman , Sudhakar Bansoid , Lienda Bashier Eltayeb , Nazia Malik , Mohammed Azam Ali , Maha Awjan Alreshidi , Mir Waqas Alam

Nanotechnology arising in wide-ranging areas, covers extensively different ranges of approaches attained from fields such as biology, chemistry, physics, and medicine engineering. Nanoparticles are a necessary part of nanotechnology effectually applied in the cure of a number of diseases. Nanoparticles have gained significant importance due to their unique properties, which differ from their bulk counterparts. These distinct properties of nanoparticles are primarily influenced by their morphology, size, and size distribution. At the nanoscale, nanoparticles exhibit behaviours that can enhance therapeutic efficacy and reduce drug toxicity. Their small size and large surface area make them promising candidates for applications such as targeted drug delivery, where they can improve treatment outcomes while minimizing adverse effects. The harmful effects of nanoparticles on the environment were critically investigated to obtain appropriate results and reduce the risk by incorporating the materials. Nanoparticles tend to penetrate the human body, clear the biological barriers to reach sensitive organs and are easily incorporated into human tissue, as well as dispersing to the hepatic tissues, heart tissues, encephalum, and GI tract. This study aims to examine a wide variety of nanoparticles, focusing on their manufacturing methods, functional characteristics, and interactions within biological systems. Particular attention will be directed towards assessing the toxicity of nanoparticles in different organs and physiological systems, yielding a thorough comprehension of their potential health hazards and the processes that drive nanoparticle-induced toxicity. This analysis will also emphasize recent developments in nanoparticle applications and safety assessment methodologies.

纳米技术的应用领域十分广泛，涵盖了生物学、化学、物理学和医学工程等领域的各种不同方法。纳米粒子是纳米技术的必要组成部分，可有效治疗多种疾病。纳米微粒因其不同于大块纳米微粒的独特性质而备受重视。纳米粒子的这些独特性质主要受其形态、尺寸和尺寸分布的影响。在纳米尺度上，纳米粒子表现出的行为可以提高疗效并降低药物毒性。纳米粒子体积小、表面积大，因此在靶向给药等应用中大有可为，既能提高治疗效果，又能最大限度地减少不良反应。我们对纳米粒子对环境的有害影响进行了严格的调查，以获得适当的结果，并通过加入这些材料来降低风险。纳米粒子容易穿透人体，通过生物屏障到达敏感器官，并很容易融入人体组织，还能分散到肝组织、心脏组织、大脑和消化道。本研究旨在研究各种纳米粒子，重点关注其制造方法、功能特性以及在生物系统中的相互作用。研究将特别关注评估纳米粒子在不同器官和生理系统中的毒性，从而全面了解纳米粒子对健康的潜在危害以及纳米粒子诱发毒性的过程。这项分析还将强调纳米粒子应用和安全评估方法的最新发展。

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引用次数: 0

Exposure of RAW264.7 macrophages to exhaust emissions (gases and PAH) and non-exhaust emissions (tire particles) induces additive or synergistic TNF-α production depending on the tire particle size 将 RAW264.7 巨噬细胞暴露于废气排放物（气体和多环芳烃）和非废气排放物（轮胎颗粒）会诱导产生相加或协同的 TNF-α，具体取决于轮胎颗粒的大小。

IF 4.8 3区医学 Q1 PHARMACOLOGY & PHARMACY

Toxicology

Pub Date : 2024-11-05 DOI: 10.1016/j.tox.2024.153990

Abderrahmane Bouredji , Riadh Lakhmi , Bogdan Muresan-Paslaru , Jérémie Pourchez , Valérie Forest

Road traffic is a major contributor to air pollution and consequently negatively affects human health. Car pollution originates both from exhaust emissions (EE) and non-exhaust emissions (NEE, such as tire and brake wear particles, erosion of road surfaces and resuspension of road dust). While the toxicity of EE and NEE has been characterized separately, their combined effects are poorly documented. However, we are constantly exposed to a mixture of pollutants and their interactions should not be neglected as they may significantly impact their toxicological profile resulting in additive, synergistic or antagonistic effects. To fill this gap, we investigated in vitro the combined toxicity of exhaust gases and benzo[a]pyrene (representative of EE) and tire particles (representative of NEE). Macrophages from the RAW264.7 cell line were exposed for 24 h to tire particles (TP) of variable size (6–113 µm), alone or in combination with exhaust gases (CO₂, CO, NO, NO₂) and benzo[a]pyrene (B[a]P) as an archetype of polycyclic aromatic hydrocarbon (PAH). The cell response was assessed in terms of cytotoxicity, proinflammatory response and oxidative stress. TP, gases and B[a]P, alone or in combination triggered neither cytotoxicity nor oxidative stress. On the contrary, a proinflammatory response was elicited with two different profiles depending on the size of the TP: TNF-α production was either slightly (with the finest TP) or strongly (with coarse TP) increased in the presence of gases and B[a]P, suggesting that the effects of TP, gases and B[a]P were either additive or synergistic, depending on TP size.

道路交通是造成空气污染的主要因素，从而对人类健康产生负面影响。汽车尾气排放（EE）和非尾气排放（NEE，如轮胎和制动器磨损颗粒、路面侵蚀和道路灰尘再悬浮）都会造成汽车污染。虽然 EE 和 NEE 的毒性已被分别描述，但它们的综合影响却鲜有记载。然而，我们经常暴露在多种污染物的混合物中，它们之间的相互作用不容忽视，因为这些相互作用可能会对它们的毒理学特征产生重大影响，从而导致叠加效应、协同效应或拮抗效应。为了填补这一空白，我们在体外研究了废气、苯并[a]芘（代表 EE）和轮胎颗粒（代表 NEE）的综合毒性。将 RAW264.7 细胞系的巨噬细胞单独或与废气（CO2、CO、NO、NO2）和作为多环芳烃（PAH）原型的苯并[a]芘（B[a]P）一起暴露于不同大小（6-113 微米）的轮胎颗粒（TP）中 24 小时。从细胞毒性、促炎症反应和氧化应激的角度对细胞反应进行了评估。TP、气体和 B[a]P 单独或混合使用都不会引发细胞毒性或氧化应激。相反，根据热塑性硫化弹性体的大小，诱发了两种不同的促炎反应：在气体和 B[a]P 的存在下，TNF-α 的产生要么略有增加（最细的热塑性硫化弹性体），要么大幅增加（粗的热塑性硫化弹性体），这表明热塑性硫化弹性体、气体和 B[a]P 的影响要么是相加的，要么是协同的，这取决于热塑性硫化弹性体的大小。

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引用次数: 0

Activation of α7 nicotinic acetylcholine receptor augments nerve growth factor action on PCtrk cells 激活α7烟碱乙酰胆碱受体可增强神经生长因子对 PCtrk 细胞的作用

IF 4.8 3区医学 Q1 PHARMACOLOGY & PHARMACY

Toxicology

Pub Date : 2024-11-04 DOI: 10.1016/j.tox.2024.153986

T. Mutoh, Y. Niimi , Akihiro Ueda

Although cigarette smoking is known to be a critical risk factor for various organ systems and cancers, accumulating evidence indicates that nicotine – a main constituent of cigarette smoking – can exert neuroprotective effects on neuronal cells through nicotinic acetylcholine receptors (nAChRs). However, the precise molecular mechanisms for nicotinic neuroprotective actions remain to be fully elucidated. In this study, we examine the effects of agonists, such as nicotine and PNU282987, on tropomyosin-related kinase (Trk)-dependent neuroprotective pathways in PC12 cells overexpressing a Trk neurotrophin receptor (PCtrk cells). We found that even considerably higher concentrations (mM range for nicotine and µM range for PN282987) of nAChR agonists exert favorable effects, such as the augmentation of nerve growth factor (NGF)-induced Trk neurotrophin receptor autophosphorylation of tyrosine residues and NGF-induced neurite extension. Moreover, nicotine upregulated reactive oxygen species (ROS) levels in the cells. ROS production was completely cancelled by pretreatment with Mito-Tempo, a mitochondria-targeted antioxidant, indicating that the main source of ROS production by nicotine was mitochondria. Furthermore, treatment with nAChR agonists appeared to induce autophagic flux, as evidenced by the upregulation of LC3-II expression in cells. Furthermore, sucrose density ultracentrifugation of nicotine-treated cells clearly disclosed the augmented recruitment of α7nAChR protein into the lipid rafts fraction of the membrane. Intriguingly, a pull-down assay of anti-Trk antibody immunoprecipitates clearly included α7nAChR protein, indicating that Trk and α7nAChR proteins form a complex. These results reveal a new molecular interaction between activated α7nAChR and Trk protein that may serve as a new molecular basis of nicotine-induced neuroprotective action.

众所周知，吸烟是导致各种器官系统和癌症的重要危险因素，但越来越多的证据表明，尼古丁--吸烟的主要成分--可以通过尼古丁乙酰胆碱受体（nAChRs）对神经细胞产生神经保护作用。然而，尼古丁神经保护作用的确切分子机制仍有待全面阐明。在本研究中，我们在过表达 Trk 神经营养素受体的 PC12 细胞（PCtrk 细胞）中研究了尼古丁和 PNU282987 等激动剂对肌球蛋白相关激酶（Trk）依赖性神经保护途径的影响。我们发现，即使浓度相当高（尼古丁在 mM 范围内，PN282987 在 µM 范围内）的 nAChR 激动剂也能产生有利影响，如增强神经生长因子（NGF）诱导的 Trk 神经营养素受体酪氨酸残基自磷酸化和 NGF 诱导的神经元延伸。此外，尼古丁还能提高细胞中的活性氧（ROS）水平。使用线粒体靶向抗氧化剂 Mito-Tempo 进行预处理可完全消除 ROS 的产生，这表明尼古丁产生 ROS 的主要来源是线粒体。此外，nAChR 激动剂似乎能诱导自噬通量，细胞中 LC3-II 的表达上调就是证明。此外，对尼古丁处理过的细胞进行蔗糖密度超速离心清楚地显示，α7nAChR 蛋白被更多地吸收到膜的脂质筏部分。耐人寻味的是，抗Trk抗体免疫沉淀物的牵引试验清楚地显示了α7nAChR蛋白，这表明Trk和α7nAChR蛋白形成了复合物。这些结果揭示了活化的α7nAChR和Trk蛋白之间新的分子相互作用，这可能是尼古丁诱导神经保护作用的新的分子基础。

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引用次数: 0

Aflatoxin B1-induced hepatotoxicity through mitochondrial dysfunction, oxidative stress, and inflammation as central pathological mechanisms: A review of experimental evidence 黄曲霉毒素 B1 通过线粒体功能障碍、氧化应激和炎症作为核心病理机制诱发肝中毒：实验证据综述。

IF 4.8 3区医学 Q1 PHARMACOLOGY & PHARMACY

Toxicology

Pub Date : 2024-11-02 DOI: 10.1016/j.tox.2024.153983

Tsholofelo P. Moloi, Khanyisani Ziqubu, Sithandiwe E. Mazibuko-Mbeje, Nonduduzo H. Mabaso, Zibele Ndlovu

Aflatoxin B₁ (AFB₁) is a class of mycotoxin known to contaminate agricultural products, animal feed and animal food products, subsequently causing detrimental effects on human and animal health. AFB₁ is the most common and potent aflatoxin found in food and contributes significantly to liver injury as well as the development of hepatocellular carcinoma. Although the liver is a primary target organ for AFB₁ toxicity and biotransformation, underlying mechanisms implicated in liver injuries induced by these mycotoxins remain to be fully elucidated for therapeutic purposes. This review aims to dissect the complexities of the pathophysiological and molecular mechanisms implicated in hepatotoxicity induced by AFB₁, including mitochondrial dysfunction, oxidative stress and hepatic inflammation. Mechanistically, AFB₁ disrupt mitochondrial bioenergetics and membrane potential, promotes mitochondrial cholesterol trafficking and induces mitophagy. Moreover, mitochondrial dysfunction may lead to hepatic oxidative stress as a consequence of uncontrolled production of reactive oxygen species and defects in the antioxidant defense system. Retrieved experimental evidence also showed that AFB₁ may lead to hepatic inflammation through gut microbiota dysbiosis, the release of DAMPs and cytokines, and immune cell recruitment. Overall, these mechanisms could be utilized as potential targets to extrapolate treatment for liver injury caused by AFB₁.

黄曲霉毒素 B1（AFB1）是一类已知会污染农产品、动物饲料和动物食品的霉菌毒素，随后会对人类和动物的健康造成不利影响。AFB1 是食物中最常见、最强效的黄曲霉毒素，对肝损伤和肝细胞癌的形成有重要作用。虽然肝脏是 AFB1 毒性和生物转化的主要靶器官，但这些霉菌毒素诱发肝损伤的潜在机制仍有待充分阐明，以达到治疗目的。本综述旨在剖析 AFB1 引起肝毒性的病理生理和分子机制的复杂性，包括线粒体功能障碍、氧化应激和肝脏炎症。从机理上讲，AFB1 会破坏线粒体的生物能和膜电位，促进线粒体胆固醇的贩运并诱导有丝分裂。此外，线粒体功能障碍可能会导致肝脏氧化应激，这是活性氧生成失控和抗氧化防御系统缺陷的结果。经检索的实验证据还表明，AFB1 可通过肠道微生物群失调、DAMPs 和细胞因子的释放以及免疫细胞的招募导致肝脏炎症。总体而言，这些机制可作为潜在靶点，用于推断 AFB1 引起的肝损伤的治疗方法。

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引用次数: 0

Amitraz mechanisms of cytotoxicity in a characterized SH-SY5Y cells spheroid model 双甲脒在特征化 SH-SY5Y 细胞球形模型中的细胞毒性机制。

IF 4.8 3区医学 Q1 PHARMACOLOGY & PHARMACY

Toxicology

Pub Date : 2024-11-01 DOI: 10.1016/j.tox.2024.153987

Felipe Franco-Campos, Mónica Fernández-Franzón, Yelko Rodríguez-Carrasco, María José Ruiz

In recent years, spheroids (tridimensional cell cultures) have emerged as a more physiologically relevant replacement for monolayer models. Their distinctive advantage is the formation of an extracellular matrix that facilitates enhanced cellular interaction and communication, approximating the conditions observed in vivo. Therefore, the potential for conducting intricate cellular and molecular techniques in these models could offer a more precise assessment of pivotal proteins within various cellular pathways of interest. Amitraz (AMZ), an acaricide classified as a formamidine chemical, has been detected in honey at concentrations exceeding legal limits. The objective of this study was to characterize a spheroid model of SH-SY5Y cells and determine the cytotoxic effect of AMZ and its mechanisms of action on this spheroid. The formation of mature spheroids was observed on the seventh day following seeding. The results obtained with SH-SY5Y spheroids were an IC₅₀ of 238.8 ± 17 µM and 224.3 ± 19 µM, respectively, after 24 and 48 h of exposure by the MTT assay. The findings revealed that AMZ did not exhibit any indications of inflammatory over-expression markers in the spheroids. Nevertheless, at 238.8 µM of AMZ, an increase incidence of late apoptosis within spheroid cells and Bcl-2 protein expression in peripheral spheroid cells were observed through annexin V and propidium iodide probe and immunofluorescence analysis. In conclusion, the results demonstrated that spheroids could be useful for an accurate assessment of toxicity, representing a viable alternative method for determining the mechanisms of action of AMZ and related compounds.

近年来，球形细胞（三维细胞培养物）已成为单层模型的一种更具生理相关性的替代物。它们的独特优势在于能形成细胞外基质，有利于增强细胞间的相互作用和交流，接近体内观察到的情况。因此，在这些模型中进行复杂的细胞和分子技术研究，可以对各种相关细胞通路中的关键蛋白进行更精确的评估。双甲脒（AMZ）是一种杀螨剂，被归类为甲脒类化学品，在蜂蜜中检测到的浓度已超过法定限值。本研究的目的是描述 SH-SY5Y 细胞球体模型的特征，并确定 AMZ 对该球体的细胞毒性作用及其作用机制。在播种后第七天观察到成熟球体的形成。通过 MTT 试验，SH-SY5Y 球形细胞暴露 24 小时和 48 小时后的 IC50 分别为 238.8 ± 17µM 和 224.3 ± 19µM。研究结果表明，AMZ 没有在球体内显示出任何炎症过度表达标记物的迹象。不过，在 AMZ 浓度为 238.8µM 时，通过附件素 V 和碘化丙啶探针以及免疫荧光分析，观察到球形细胞内晚期凋亡发生率增加，外周球形细胞中 Bcl-2 蛋白表达增加。总之，研究结果表明，球形细胞可用于准确评估毒性，是确定 AMZ 和相关化合物作用机制的另一种可行方法。

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引用次数: 0

Unraveling the enigma of cardiac damage caused by lead: Understanding the intricate relationship between oxidative stress and other multifactorial mechanisms 揭开铅对心脏损害之谜：了解氧化应激与其他多因素机制之间错综复杂的关系。

IF 4.8 3区医学 Q1 PHARMACOLOGY & PHARMACY

Toxicology

Pub Date : 2024-10-29 DOI: 10.1016/j.tox.2024.153984

Anjali Rajpoot, Tanya Aggarwal, Veena Sharma

Lead (Pb) exposure remains a pressing concern in the realm of public health, with a mounting body of evidence underscoring its adverse impact on cardiovascular well-being. The exposure to Lead instigates the production of reactive oxygen species (ROS), leading to consequential cellular and physiological damage and a perturbation in redox equilibrium. The resultant oxidative stress, induced by ROS, disrupts endothelial functionality, propagates inflammatory processes, and initiates vascular remodeling, collectively contributing to the advancement of cardiovascular diseases (CVDs). The objective of this current review is to comprehensively expound upon the intricate mechanisms through which Lead induced toxicity affects cardiac cells. Additionally, it briefly addresses the ramifications of Lead exposure on the development of three interconnected cardiovascular conditions: atherosclerosis, hypertension, and myocardial infarction. Furthermore, the discourse delves into the specific repercussions of Lead exposure on lipid metabolism, blood pressure regulation, and cardiac performance, culminating in the initiation and progression of atherosclerotic plaque formation, elevated blood pressure, and an augmented risk of myocardial infarction. By understanding these intricate mechanisms, targeted interventions may be devised to counteract the deleterious effects of Lead on cardiovascular health. Thus, this review offers novel avenues for preventive and therapeutic strategies, ultimately serving to alleviate the burden of cardiovascular diseases associated with Lead toxicity.

铅（Pb）暴露仍然是公共卫生领域的一个紧迫问题，越来越多的证据表明铅对心血管健康有不利影响。接触铅会产生活性氧（ROS），导致细胞和生理损伤以及氧化还原平衡紊乱。由 ROS 引发的氧化应激会破坏内皮功能、传播炎症过程并引发血管重塑，从而共同导致心血管疾病（CVDs）的恶化。本综述旨在全面阐述铅诱导的毒性影响心脏细胞的复杂机制。此外，它还简要论述了铅暴露对动脉粥样硬化、高血压和心肌梗塞这三种相互关联的心血管疾病发展的影响。此外，论文还深入探讨了铅暴露对脂质代谢、血压调节和心脏功能的具体影响，最终导致动脉粥样硬化斑块形成、血压升高和心肌梗死风险增加。通过了解这些错综复杂的机制，可以设计出有针对性的干预措施来抵消铅对心血管健康的有害影响。因此，本综述为预防和治疗策略提供了新的途径，最终有助于减轻与铅毒性相关的心血管疾病负担。

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引用次数: 0

E-waste in the environment: Unveiling the sources, carcinogenic links, and sustainable management strategies 环境中的电子废物：揭示来源、致癌联系和可持续管理战略。

IF 4.8 3区医学 Q1 PHARMACOLOGY & PHARMACY

Toxicology

Pub Date : 2024-10-26 DOI: 10.1016/j.tox.2024.153981

Md Abdullah , Satadal Adhikary , Suchandra Bhattacharya , Sudharani Hazra , Abhratanu Ganguly , Sayantani Nanda , Prem Rajak

E-waste refers to the electrical and electronic equipment discarded without the intent of reuse or at the end of its functional lifespan. In 2022, approximately 62 billion kg of e-waste, equivalent to 7.8 kg per capita, was generated globally. With an alarming annual growth of approximately 2 million metric tonnes, e-waste production may exceed 82 billion kg by 2030. Improper disposal of e-waste can be detrimental to human health and the entire biosphere. E-waste encompasses a wide range of materials, including heavy metals, Polychlorinated Biphenyls (PCBs), Per- and Polyfluoroalkyl Substances (PFAS), Polycyclic Aromatic Hydrocarbons (PAHs), Polychlorinated Dibenzo-dioxins and -furans (PCDD/Fs), Polybrominated Diphenyl Ethers (PBDEs), and radioactive elements. E-waste, when disposed inappropriately can directly contaminate the aquatic and terrestrial environment, leading to human exposure through ingestion, inhalation, dermal absorption, and trans-placental transfer. These detrimental contaminants can directly enter the human body from the environment and may fuel carcinogenesis by modulating cell cycle proteins, redox homeostasis, and mutations. Heavy metals such as cadmium, mercury, arsenic, lead, chromium, and nickel, along with organic pollutants like PAHs, PCBs, PBDEs, PFAS, and radioactive elements, play a crucial role in inducing malignancy. Effective collection, sorting, proper recycling, and appropriate disposal techniques are essential to reduce environmental contamination with e-waste-derived chemicals. Hence, this comprehensive review aims to unravel the global environmental burden of e-waste and its links to carcinogenesis in humans. Furthermore, it provides an inclusive discussion on potential treatment approaches to minimize environmental e-waste contamination.

电子废物指的是在没有再利用意图的情况下选择丢弃或在其功能寿命结束时丢弃的电气和电子设备。2022 年，全球产生的电子垃圾约为 620 亿公斤，相当于人均 7.8 公斤。随着每年约 200 万公吨的惊人增长，到 2030 年，电子废物产量可能超过 820 亿公斤。电子垃圾的不当处置会损害人类健康和整个生物圈。电子垃圾包含多种化学物质，包括重金属、多氯联苯 (PCB)、全氟和多氟烷基物质 (PFAS)、多环芳香烃 (PAH)、多氯二苯并对二恶英和呋喃 (PCDD/Fs)、多溴联苯醚 (PBDE) 和放射性元素。电子废物设备的不当处置会直接污染水生和陆地环境，导致人类通过摄入、吸入、皮肤吸收和经胎盘转移等方式接触这些污染物。这些污染物可从环境中直接进入人体，通过调节细胞周期蛋白、诱导氧化应激和突变，有可能助长癌变。镉、汞、砷、铅、铬和镍等重金属，以及多环芳烃、多氯联苯、多溴联苯醚、全氟醚和放射性元素等有机污染物，在诱发人类恶性肿瘤方面发挥着至关重要的作用。有效的收集、分类、适当的回收和适当的处置技术对于减少电子废物衍生化学物质对环境的污染至关重要。因此，本综述旨在揭示电子废物对全球环境造成的负担及其与人类致癌的联系。此外，它还对潜在的处理方法进行了全面讨论，以最大限度地减少电子废物对环境的污染。

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引用次数: 0

Hematological, cardiovascular and oxidative DNA damage markers associated with heavy metal exposure in electronic waste (e-waste) workers of Bangladesh 与孟加拉国电子废物工人接触重金属有关的血液学、心血管和 DNA 氧化损伤指标。

IF 4.8 3区医学 Q1 PHARMACOLOGY & PHARMACY

Toxicology

Pub Date : 2024-10-24 DOI: 10.1016/j.tox.2024.153978

Sarker Masud Parvez , M Mamun Huda , Mahbubur Rahman , Farjana Jahan , Masatake Fujimura , Shaikh Sharif Hasan , Nirupam Aich , Abul Hares , Zahir Islam , Rubhana Raqib , Luke D Knibbs , Peter D Sly

Electronic waste (e-waste) contains hazardous elements such as lead (Pb), cadmium (Cd), mercury (Hg), and other toxic elements that pose significant health risks to the population directly exposed. We recruited 199 e-waste recycling workers and 104 non-exposed workers in Bangladesh and analyzed heavy metals in blood and hair, as well as hematological and cardiovascular parameters including, blood lipids and blood pressure. We fitted quantile regression models at 0.5 quantile to evaluate the impact of blood Pb, Cd, and total hair Hg (THg) on hematological and cardiovascular parameters and the role of oxidative DNA damage (8-OHdG as a biomarker) in mediatin the relationship between exposures and outcomes. Exposed workers had elevated median blood Pb (11.89 vs. 3.63 µg/dL), moderate blood Cd (1.04 vs. 0.99 µg/L), and lower level of THg (0.38 vs. 0.57 ppm) in hair than non-exposed workers. Adjusted estimates showed that Pb was positively associated with red blood cell (RBC), eosinophil count, eosinophil percentage; and negatively associated with mean platelet volume (MPV), platelet large cell ratio (P-LCR) and platelet volume distribution width (PDW) (all p≤0.05). Cd was only associated with 0.57 units increase in red blood cell distribution width (RDW) percentage (95 % CI: 0.18, 0.95). In cardiovascular outcomes, Pb was associated with 1.42 units decrease in triglyceride, 1.58 units increase in low-density lipoprotein (LDL), 0.07 units increase in LDL/HDL and 0.49 units increase in systolic blood pressure (all p≤0.05). No associations were observed between THg and hematological or cardiovascular parameters. Urinary 8-OHdG concentrations were lower, and it did not mediate exposure-outcome relationships (all p≥0.05). Our data imply that e-waste exposure impairs hematological parameters, blood lipids, and blood pressure secondary to elevated Pb levels and poses a threat to exposed individuals. As such, continuous monitoring in longitudinal studies is warranted to assess the dose-response relationship and identify effective control measures.

电子废物（e-waste）中含有有害元素，如铅（Pb）、镉（Cd）、汞（Hg）和其他有毒元素，对直接接触这些元素的人群构成重大健康风险。我们在孟加拉国招募了 199 名电子垃圾回收工人和 104 名未接触电子垃圾的工人，分析了他们血液和头发中的重金属含量，以及血液和心血管参数，包括血脂和血压。我们建立了 0.5 量级的量级回归模型，以评估血液中铅、镉和毛发中总汞 (THg) 对血液学和心血管参数的影响，以及氧化 DNA 损伤（8-OHdG 作为生物标志物）在调节暴露与结果之间关系中的作用。与非暴露工人相比，暴露工人的血液中位数铅升高（11.89µg/dL 对 3.63µg/dL），血液中位数镉升高（1.04µg/L 对 0.99µg/L），头发中的四氢大麻酚水平较低（0.38ppm 对 0.57ppm）。调整后的估计值显示，铅与红细胞（RBC）、嗜酸性粒细胞计数、嗜酸性粒细胞百分比呈正相关；与平均血小板体积（MPV）、血小板大细胞比率（P-LCR）和血小板体积分布宽度（PDW）呈负相关（所有 p 均小于 0.05）。镉仅与红细胞分布宽度（RDW）百分比增加 0.57 个单位有关（95% CI：0.18，0.95）。在心血管结果方面，铅与甘油三酯降低 1.42 个单位、低密度脂蛋白（LDL）升高 1.58 个单位、低密度脂蛋白/高密度脂蛋白升高 0.07 个单位和收缩压升高 0.49 个单位有关（均 p≤0.05）。没有观察到 THg 与血液学或心血管参数之间有任何关联。尿液中 8-OHdG 的浓度较低，但它并不介导接触与结果之间的关系（所有 p 均≥0.05）。我们的数据表明，暴露于电子废物会因铅含量升高而损害血液参数、血脂和血压，并对暴露者构成威胁。因此，有必要在纵向研究中进行持续监测，以评估剂量-反应关系并确定有效的控制措施。

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引用次数: 0

Prenatal exposure to di-n-butyl phthalate promotes RIPK1-regulated necroptosis of uroepithelial cells and induces hypospadias through the epithelial-mesenchymal transition process in newborn male rats 产前暴露于邻苯二甲酸二正丁酯会促进 RIPK1 调节的尿路上皮细胞坏死，并通过上皮-间质转化过程诱发新生雄性大鼠尿道下裂。

IF 4.8 3区医学 Q1 PHARMACOLOGY & PHARMACY

Toxicology

Pub Date : 2024-10-24 DOI: 10.1016/j.tox.2024.153982

Lei Wu , Zhiwen Xie , Tiewen Li , Xincan Chen , Juntao Jiang , Fei Shi , Yongqing Zhang , Xinyu Xu , Shujie Xia , Wenlan Sun

Maternal exposure to di-n-butyl phthalate (DBP) has been linked to the induction of hypospadias; however, the underlying mechanism remains unclear. Necroptosis is reported to be implicated in developmental malformations. This study aimed to investigate the underlying mechanism of necroptosis in the development of hypospadias. DBP was dissolved in corn oil, and pregnant rats were administered a precisely measured dose of DBP (750 mg/kg/day) via gastric intubation from gestation day 14–18. Control rats received only corn oil. The day of birth was considered postnatal day (PND) 1. Male hypospadias rats were identified on PND 7. Genital tubercle tissues were collected and stored at −80°C for subsequent PCR analysis, cryopreserved in liquid nitrogen for western blot, or fixed in formalin for immunohistochemistry (IHC) staining. IHC staining and western blot analysis revealed increased expression of RIPK1 and necroptosis markers in genital tubercle (GT) tissue compared to the control group. Additionally, higher levels of EMT and impaired androgen receptor expression were observed in GT tissue. Exposure to increased DBP concentrations in rat primary uroepithelial cells (PUCs) led to elevated ROS production. Necroptosis markers and EMT expression levels were upregulated in PUCs following DBP incubation. Notably, treatment with DBP combined with necrostatin-1, a necroptosis inhibitor, reduced the expression of EMT markers and ROS production compared to DBP treatment alone. In vitro studies further revealed that DBP-induced necroptosis promoted the degradation of E-cadherin through the ubiquitin-proteasome pathway in PUCs. Our findings suggest that maternal exposure to DBP promotes necroptosis in uroepithelial cells by elevating ROS level and EMT status. Thus, necroptosis may play an essential role in the development of hypospadias.

母体接触邻苯二甲酸二正丁酯（DBP）与尿道下裂的诱发有关，但其根本机制仍不清楚。据报道，坏死与发育畸形有关。本研究旨在探究尿道下裂发生的坏死机制。将 DBP 溶解在玉米油中，从妊娠第 14 天到第 18 天，通过插胃给妊娠大鼠注射精确计量的 DBP 剂量（750 毫克/千克/天）。对照组大鼠只摄入玉米油。雄性尿道下裂大鼠在出生后第 7 天进行鉴定。收集生殖器结节组织并保存在 -80°C 温度下，用于随后的 PCR 分析；在液氮中冷冻保存，用于 Western 印迹；或在福尔马林中固定，用于免疫组织化学 (IHC) 染色。IHC染色和Western印迹分析显示，与对照组相比，生殖器结节（GT）组织中RIPK1和坏死标志物的表达增加。此外，在 GT 组织中观察到更高水平的 EMT 和受损的雄激素受体表达。大鼠原发性尿路上皮细胞（PUCs）暴露于浓度增加的 DBP 会导致 ROS 生成增加。在 DBP 培养后，PUC 中坏死标志物和 EMT 表达水平上调。值得注意的是，与单独使用 DBP 处理相比，DBP 与坏死抑制剂 necrostatin-1 结合使用可减少 EMT 标记物的表达和 ROS 的产生。体外研究进一步发现，DBP 诱导的坏死促进了 E-cadherin 通过泛素-蛋白酶体途径在 PUC 中降解。我们的研究结果表明，母体暴露于 DBP 会通过提高 ROS 水平和 EMT 状态来促进尿路上皮细胞的坏死。因此，坏死可能在尿道下裂的发展过程中扮演着重要角色。

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引用次数: 0