Pub Date : 2024-10-08DOI: 10.1186/s12989-024-00594-6
David G Luglio, Kayla Rae Farrell, Terry Gordon
Background: Subway systems are becoming increasingly common worldwide transporting large populations in major cities. PM2.5 concentrations have been demonstrated to be exceptionally high when underground, however. Studies on the impact of subway PM exposure on cardiopulmonary health in the United States are limited.
Methods: Healthy volunteers in New York City were exposed to a 2-h visit on the 9th Street Station platform on the Port Authority Trans-Hudson train system. Blood pressure, heart rate variability (HRV), spirometry, and forced impulse oscillometry were measured, and urine, blood spot, and nasal swab biosamples were collected for cytokine analysis at the end of the 2-h exposure period. These endpoints were compared against individual control measurements collected after 2-h in a "clean" control space. In addition to paired comparisons, mixed effects models with subject as a random effect were employed to investigate the effect of the PM2.5 concentrations and visit type (i.e., subway vs. control).
Results: Mean PM2.5 concentrations on the platform and during the control visit were 293.6 ± 65.7 (SD) and 4.6 ± 1.9 µg/m3, respectively. There was no change in any of the health metrics, but there was a non-significant trend for SDNN to be lower after subway exposure compared to control exposure. Total symptomatic scores did increase post-subway exposure compared to reported values prior to exposure or after the control visit. No significant changes in cytokine concentrations in any specimen type were observed. Mixed-effects models mostly corroborated these paired comparisons.
Conclusions: Acute exposures to PM on a subway platform do not cause measurable cardiopulmonary effects apart from reductions in HRV and increases in symptoms in healthy volunteers. These findings match other studies that found little to no changes in lung function and blood pressure after exposure in underground subway stations. Future work should still target potentially more vulnerable populations, such as individuals with asthma or those who spend increased time underground on the subway such as transit workers.
{"title":"A pilot study of the cardiopulmonary effects in healthy volunteers after exposure to high levels of PM<sub>2.5</sub> in a New York City subway station.","authors":"David G Luglio, Kayla Rae Farrell, Terry Gordon","doi":"10.1186/s12989-024-00594-6","DOIUrl":"10.1186/s12989-024-00594-6","url":null,"abstract":"<p><strong>Background: </strong>Subway systems are becoming increasingly common worldwide transporting large populations in major cities. PM<sub>2.5</sub> concentrations have been demonstrated to be exceptionally high when underground, however. Studies on the impact of subway PM exposure on cardiopulmonary health in the United States are limited.</p><p><strong>Methods: </strong>Healthy volunteers in New York City were exposed to a 2-h visit on the 9th Street Station platform on the Port Authority Trans-Hudson train system. Blood pressure, heart rate variability (HRV), spirometry, and forced impulse oscillometry were measured, and urine, blood spot, and nasal swab biosamples were collected for cytokine analysis at the end of the 2-h exposure period. These endpoints were compared against individual control measurements collected after 2-h in a \"clean\" control space. In addition to paired comparisons, mixed effects models with subject as a random effect were employed to investigate the effect of the PM<sub>2.5</sub> concentrations and visit type (i.e., subway vs. control).</p><p><strong>Results: </strong>Mean PM<sub>2.5</sub> concentrations on the platform and during the control visit were 293.6 ± 65.7 (SD) and 4.6 ± 1.9 µg/m<sup>3</sup>, respectively. There was no change in any of the health metrics, but there was a non-significant trend for SDNN to be lower after subway exposure compared to control exposure. Total symptomatic scores did increase post-subway exposure compared to reported values prior to exposure or after the control visit. No significant changes in cytokine concentrations in any specimen type were observed. Mixed-effects models mostly corroborated these paired comparisons.</p><p><strong>Conclusions: </strong>Acute exposures to PM on a subway platform do not cause measurable cardiopulmonary effects apart from reductions in HRV and increases in symptoms in healthy volunteers. These findings match other studies that found little to no changes in lung function and blood pressure after exposure in underground subway stations. Future work should still target potentially more vulnerable populations, such as individuals with asthma or those who spend increased time underground on the subway such as transit workers.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":"21 1","pages":"42"},"PeriodicalIF":7.2,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11460011/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142392369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-29DOI: 10.1186/s12989-024-00601-w
Kayla Nguyen-Alley, Sarah Daniel, Danielle T Phillippi, Tyler D Armstrong, Bailee Johnson, Winston Ihemeremadu, Amie K Lund
Background: Both exposure to air pollutants and obesity are associated with increased incidence and severity of COVID-19 infection; however, the mechanistic pathways involved are not well-characterized. After being primed by the transmembrane protease serine 2 (TMPRSS2) or furin protease, SARS-CoV-2 uses the angiotensin-converting enzyme (ACE)-2 receptor to enter respiratory epithelial cells. The androgen receptor (AR) is known to regulate both TMPRSS2 and ACE2 expression, and neuropilin-1 (NRP1) is a proposed coreceptor for SARS-CoV-2; thus, altered expression of these factors may promote susceptibility to infection. As such, this study investigated the hypothesis that inhalational exposure to traffic-generated particulate matter (diesel exhaust particulate; DEP) increases the expression of those pathways that mediate SARS-CoV-2 infection and susceptibility, which is exacerbated by the consumption of a high-fat (HF) diet.
Methods: Four- to six-week-old male C57BL/6 mice fed either regular chow or a HF diet (HF, 45% kcal from fat) were randomly assigned to be exposed via oropharyngeal aspiration to 35 µg DEP suspended in 35 µl 0.9% sterile saline or sterile saline only (control) twice a week for 30 days. Furthermore, as previous studies have shown that probiotic treatment can protect against exposure-related inflammatory outcomes in the lungs, a subset of study animals fed a HF diet were concurrently treated with 0.3 g/day Winclove Ecologic® Barrier probiotics in their drinking water throughout the study.
Results: Our results revealed that the expression of ACE2 protein increased with DEP exposure and that TMPRSS2, AR, NRP1, and furin protein expression increased with DEP exposure in conjunction with a HF diet. These DEP ± HF diet-mediated increases in expression were mitigated with probiotic treatment.
Conclusion: These findings suggest that inhalational exposure to air pollutants in conjunction with the consumption of a HF diet contributes to a more susceptible lung environment to SARS-CoV-2 infection and that probiotic treatment could be beneficial as a preventative measure.
{"title":"Diesel exhaust particle inhalation in conjunction with high-fat diet consumption alters the expression of pulmonary SARS-COV-2 infection pathways, which is mitigated by probiotic treatment in C57BL/6 male mice.","authors":"Kayla Nguyen-Alley, Sarah Daniel, Danielle T Phillippi, Tyler D Armstrong, Bailee Johnson, Winston Ihemeremadu, Amie K Lund","doi":"10.1186/s12989-024-00601-w","DOIUrl":"https://doi.org/10.1186/s12989-024-00601-w","url":null,"abstract":"<p><strong>Background: </strong>Both exposure to air pollutants and obesity are associated with increased incidence and severity of COVID-19 infection; however, the mechanistic pathways involved are not well-characterized. After being primed by the transmembrane protease serine 2 (TMPRSS2) or furin protease, SARS-CoV-2 uses the angiotensin-converting enzyme (ACE)-2 receptor to enter respiratory epithelial cells. The androgen receptor (AR) is known to regulate both TMPRSS2 and ACE2 expression, and neuropilin-1 (NRP1) is a proposed coreceptor for SARS-CoV-2; thus, altered expression of these factors may promote susceptibility to infection. As such, this study investigated the hypothesis that inhalational exposure to traffic-generated particulate matter (diesel exhaust particulate; DEP) increases the expression of those pathways that mediate SARS-CoV-2 infection and susceptibility, which is exacerbated by the consumption of a high-fat (HF) diet.</p><p><strong>Methods: </strong>Four- to six-week-old male C57BL/6 mice fed either regular chow or a HF diet (HF, 45% kcal from fat) were randomly assigned to be exposed via oropharyngeal aspiration to 35 µg DEP suspended in 35 µl 0.9% sterile saline or sterile saline only (control) twice a week for 30 days. Furthermore, as previous studies have shown that probiotic treatment can protect against exposure-related inflammatory outcomes in the lungs, a subset of study animals fed a HF diet were concurrently treated with 0.3 g/day Winclove Ecologic<sup>®</sup> Barrier probiotics in their drinking water throughout the study.</p><p><strong>Results: </strong>Our results revealed that the expression of ACE2 protein increased with DEP exposure and that TMPRSS2, AR, NRP1, and furin protein expression increased with DEP exposure in conjunction with a HF diet. These DEP ± HF diet-mediated increases in expression were mitigated with probiotic treatment.</p><p><strong>Conclusion: </strong>These findings suggest that inhalational exposure to air pollutants in conjunction with the consumption of a HF diet contributes to a more susceptible lung environment to SARS-CoV-2 infection and that probiotic treatment could be beneficial as a preventative measure.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":"21 1","pages":"40"},"PeriodicalIF":7.2,"publicationDate":"2024-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11439268/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142351663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-27DOI: 10.1186/s12989-024-00599-1
Todd Gouin, Robert Ellis-Hutchings, Mark Pemberton, Bianca Wilhelmus
<p><strong>Background: </strong>There has been an exponential increase in the number of studies reporting on the toxicological effects associated with exposure to nano and microplastic particles (NMPs). The majority of these studies, however, have used monodispersed polystyrene microspheres (PSMs) as 'model' particles. Here we review the differences between the manufacture and resulting physicochemical properties of polystyrene used in commerce and the PSMs most commonly used in toxicity studies.</p><p><strong>Main body: </strong>In general, we demonstrate that significant complexity exists as to the properties of polystyrene particles. Differences in chemical composition, size, shape, surface functionalities and other aspects raise doubt as to whether PSMs are fit-for-purpose for the study of potential adverse effects of naturally occurring NMPs. A realistic assessment of potential health implications of the exposure to environmental NMPs requires better characterisation of the particles, a robust mechanistic understanding of their interactions and effects in biological systems as well as standardised protocols to generate relevant model particles. It is proposed that multidisciplinary engagement is necessary for the development of a timely and effective strategy towards this end. We suggest a holistic framework, which must be supported by a multidisciplinary group of experts to work towards either providing access to a suite of environmentally relevant NMPs and/or developing guidance with respect to best practices that can be adopted by research groups to generate and reliably use NMPs. It is emphasized that there is a need for this group to agree to a consensus regarding what might best represent a model NMP that is consistent with environmental exposure for human health, and which can be used to support a variety of ongoing research needs, including those associated with exposure and hazard assessment, mechanistic toxicity studies, toxicokinetics and guidance regarding the prioritization of plastic and NMPs that likely represent the greatest risk to human health. It is important to acknowledge, however, that establishing a multidisciplinary group, or an expert community of practice, represents a non-trivial recommendation, and will require significant resources in terms of expertise and funding.</p><p><strong>Conclusion: </strong>There is currently an opportunity to bring together a multidisciplinary group of experts, including polymer chemists, material scientists, mechanical engineers, exposure and life-cycle assessment scientists, toxicologists, microbiologists and analytical chemists, to provide leadership and guidance regarding a consensus on defining what best represents environmentally relevant NMPs. We suggest that given the various complex issues surrounding the environmental and human health implications that exposure to NMPs represents, that a multidisciplinary group of experts are thus critical towards helping to progress the harm
{"title":"Addressing the relevance of polystyrene nano- and microplastic particles used to support exposure, toxicity and risk assessment: implications and recommendations.","authors":"Todd Gouin, Robert Ellis-Hutchings, Mark Pemberton, Bianca Wilhelmus","doi":"10.1186/s12989-024-00599-1","DOIUrl":"https://doi.org/10.1186/s12989-024-00599-1","url":null,"abstract":"<p><strong>Background: </strong>There has been an exponential increase in the number of studies reporting on the toxicological effects associated with exposure to nano and microplastic particles (NMPs). The majority of these studies, however, have used monodispersed polystyrene microspheres (PSMs) as 'model' particles. Here we review the differences between the manufacture and resulting physicochemical properties of polystyrene used in commerce and the PSMs most commonly used in toxicity studies.</p><p><strong>Main body: </strong>In general, we demonstrate that significant complexity exists as to the properties of polystyrene particles. Differences in chemical composition, size, shape, surface functionalities and other aspects raise doubt as to whether PSMs are fit-for-purpose for the study of potential adverse effects of naturally occurring NMPs. A realistic assessment of potential health implications of the exposure to environmental NMPs requires better characterisation of the particles, a robust mechanistic understanding of their interactions and effects in biological systems as well as standardised protocols to generate relevant model particles. It is proposed that multidisciplinary engagement is necessary for the development of a timely and effective strategy towards this end. We suggest a holistic framework, which must be supported by a multidisciplinary group of experts to work towards either providing access to a suite of environmentally relevant NMPs and/or developing guidance with respect to best practices that can be adopted by research groups to generate and reliably use NMPs. It is emphasized that there is a need for this group to agree to a consensus regarding what might best represent a model NMP that is consistent with environmental exposure for human health, and which can be used to support a variety of ongoing research needs, including those associated with exposure and hazard assessment, mechanistic toxicity studies, toxicokinetics and guidance regarding the prioritization of plastic and NMPs that likely represent the greatest risk to human health. It is important to acknowledge, however, that establishing a multidisciplinary group, or an expert community of practice, represents a non-trivial recommendation, and will require significant resources in terms of expertise and funding.</p><p><strong>Conclusion: </strong>There is currently an opportunity to bring together a multidisciplinary group of experts, including polymer chemists, material scientists, mechanical engineers, exposure and life-cycle assessment scientists, toxicologists, microbiologists and analytical chemists, to provide leadership and guidance regarding a consensus on defining what best represents environmentally relevant NMPs. We suggest that given the various complex issues surrounding the environmental and human health implications that exposure to NMPs represents, that a multidisciplinary group of experts are thus critical towards helping to progress the harm","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":"21 1","pages":"39"},"PeriodicalIF":7.2,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11429038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142351662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-19DOI: 10.1186/s12989-024-00600-x
Svenja Offer, Sebastiano Di Bucchianico, Hendryk Czech, Michal Pardo, Jana Pantzke, Christoph Bisig, Eric Schneider, Stefanie Bauer, Elias J. Zimmermann, Sebastian Oeder, Elena Hartner, Thomas Gröger, Rasha Alsaleh, Christian Kersch, Till Ziehm, Thorsten Hohaus, Christopher P. Rüger, Simone Schmitz-Spanke, Jürgen Schnelle-Kreis, Martin Sklorz, Astrid Kiendler-Scharr, Yinon Rudich, Ralf Zimmermann
The formation of secondary organic aerosols (SOA) by atmospheric oxidation reactions substantially contributes to the burden of fine particulate matter (PM2.5), which has been associated with adverse health effects (e.g., cardiovascular diseases). However, the molecular and cellular effects of atmospheric aging on aerosol toxicity have not been fully elucidated, especially in model systems that enable cell-to-cell signaling. In this study, we aimed to elucidate the complexity of atmospheric aerosol toxicology by exposing a coculture model system consisting of an alveolar (A549) and an endothelial (EA.hy926) cell line seeded in a 3D orientation at the air‒liquid interface for 4 h to model aerosols. Simulation of atmospheric aging was performed on volatile biogenic (β-pinene) or anthropogenic (naphthalene) precursors of SOA condensing on soot particles. The similar physical properties for both SOA, but distinct differences in chemical composition (e.g., aromatic compounds, oxidation state, unsaturated carbonyls) enabled to determine specifically induced toxic effects of SOA. In A549 cells, exposure to naphthalene-derived SOA induced stress-related airway remodeling and an early type I immune response to a greater extent. Transcriptomic analysis of EA.hy926 cells not directly exposed to aerosol and integration with metabolome data indicated generalized systemic effects resulting from the activation of early response genes and the involvement of cardiovascular disease (CVD) -related pathways, such as the intracellular signal transduction pathway (PI3K/AKT) and pathways associated with endothelial dysfunction (iNOS; PDGF). Greater induction following anthropogenic SOA exposure might be causative for the observed secondary genotoxicity. Our findings revealed that the specific effects of SOA on directly exposed epithelial cells are highly dependent on the chemical identity, whereas non directly exposed endothelial cells exhibit more generalized systemic effects with the activation of early stress response genes and the involvement of CVD-related pathways. However, a greater correlation was made between the exposure to the anthropogenic SOA compared to the biogenic SOA. In summary, our study highlights the importance of chemical aerosol composition and the use of cell systems with cell-to-cell interplay on toxicological outcomes.
大气氧化反应形成的二次有机气溶胶（SOA）大大加重了细颗粒物（PM2.5）的负担，而细颗粒物与不良健康影响（如心血管疾病）有关。然而，大气老化对气溶胶毒性的分子和细胞影响尚未完全阐明，尤其是在能够进行细胞间信号传递的模型系统中。在本研究中，我们将肺泡细胞系（A549）和内皮细胞系（EA.hy926）以三维方向播种在空气-液体界面上，并将其暴露在气溶胶模型中 4 小时，旨在阐明大气气溶胶毒理学的复杂性。对凝结在烟尘颗粒上的挥发性生物 SOA（β-蒎烯）或人为 SOA（萘）前体进行了大气老化模拟。这两种 SOA 的物理特性相似，但化学成分（如芳香族化合物、氧化态、不饱和羰基）却有明显差异，因此能够确定 SOA 的特定诱导毒性效应。在 A549 细胞中，暴露于萘衍生的 SOA 会在更大程度上诱导应激相关的气道重塑和早期 I 型免疫反应。对未直接暴露于气溶胶的 EA.hy926 细胞进行的转录组分析以及与代谢组数据的整合表明，早期反应基因的激活和心血管疾病（CVD）相关通路（如细胞内信号转导通路（PI3K/AKT）和与内皮功能障碍相关的通路（iNOS；PDGF））的参与导致了普遍的全身效应。人为暴露于 SOA 后产生的更大诱导作用可能是观察到的继发性基因毒性的原因。我们的研究结果表明，SOA 对直接暴露的上皮细胞的特异性影响高度依赖于化学特性，而非直接暴露的内皮细胞则表现出更普遍的系统性影响，早期应激反应基因被激活，心血管疾病相关通路参与其中。不过，与生物源 SOA 相比，人为 SOA 暴露之间的相关性更大。总之，我们的研究强调了化学气溶胶成分以及使用细胞间相互作用的细胞系统对毒理学结果的重要性。
{"title":"The chemical composition of secondary organic aerosols regulates transcriptomic and metabolomic signaling in an epithelial-endothelial in vitro coculture","authors":"Svenja Offer, Sebastiano Di Bucchianico, Hendryk Czech, Michal Pardo, Jana Pantzke, Christoph Bisig, Eric Schneider, Stefanie Bauer, Elias J. Zimmermann, Sebastian Oeder, Elena Hartner, Thomas Gröger, Rasha Alsaleh, Christian Kersch, Till Ziehm, Thorsten Hohaus, Christopher P. Rüger, Simone Schmitz-Spanke, Jürgen Schnelle-Kreis, Martin Sklorz, Astrid Kiendler-Scharr, Yinon Rudich, Ralf Zimmermann","doi":"10.1186/s12989-024-00600-x","DOIUrl":"https://doi.org/10.1186/s12989-024-00600-x","url":null,"abstract":"The formation of secondary organic aerosols (SOA) by atmospheric oxidation reactions substantially contributes to the burden of fine particulate matter (PM2.5), which has been associated with adverse health effects (e.g., cardiovascular diseases). However, the molecular and cellular effects of atmospheric aging on aerosol toxicity have not been fully elucidated, especially in model systems that enable cell-to-cell signaling. In this study, we aimed to elucidate the complexity of atmospheric aerosol toxicology by exposing a coculture model system consisting of an alveolar (A549) and an endothelial (EA.hy926) cell line seeded in a 3D orientation at the air‒liquid interface for 4 h to model aerosols. Simulation of atmospheric aging was performed on volatile biogenic (β-pinene) or anthropogenic (naphthalene) precursors of SOA condensing on soot particles. The similar physical properties for both SOA, but distinct differences in chemical composition (e.g., aromatic compounds, oxidation state, unsaturated carbonyls) enabled to determine specifically induced toxic effects of SOA. In A549 cells, exposure to naphthalene-derived SOA induced stress-related airway remodeling and an early type I immune response to a greater extent. Transcriptomic analysis of EA.hy926 cells not directly exposed to aerosol and integration with metabolome data indicated generalized systemic effects resulting from the activation of early response genes and the involvement of cardiovascular disease (CVD) -related pathways, such as the intracellular signal transduction pathway (PI3K/AKT) and pathways associated with endothelial dysfunction (iNOS; PDGF). Greater induction following anthropogenic SOA exposure might be causative for the observed secondary genotoxicity. Our findings revealed that the specific effects of SOA on directly exposed epithelial cells are highly dependent on the chemical identity, whereas non directly exposed endothelial cells exhibit more generalized systemic effects with the activation of early stress response genes and the involvement of CVD-related pathways. However, a greater correlation was made between the exposure to the anthropogenic SOA compared to the biogenic SOA. In summary, our study highlights the importance of chemical aerosol composition and the use of cell systems with cell-to-cell interplay on toxicological outcomes. ","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":"11 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142259929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-18DOI: 10.1186/s12989-024-00598-2
Jiaxin Shang, Jun Yan, He Lou, Rongshang Shou, Yingqi Zhan, Xiaoyan Lu, Xiaohui Fan
Following the announcement by the European Food Safety Authority that the food additive titanium dioxide (E 171) is unsafe for human consumption, and the subsequent ban by the European Commission, concerns have intensified over the potential risks E 171 poses to human vital organs. The liver is the main organ for food-grade nanoparticle metabolism. It is increasingly being found that epigenetic changes may play an important role in nanomaterial-induced hepatotoxicity. However, the profound effects of E 171 on the liver, especially at the epigenetic level, remain largely unknown. Mice were exposed orally to human-relevant doses of two types of E 171 mixed in diet for 28 and/or 84 days. Conventional toxicology and global DNA methylation analyses were performed to assess E 171-induced hepatotoxicity and epigenetic changes. Whole genome bisulfite sequencing and further ferroptosis protein detection were used to reveal E 171-induced changes in liver methylation profiles and toxic mechanisms. Exposed to E 171 for 28 and/or 84 days resulted in reduced global DNA methylation and hydroxymethylation in the liver of mice. E 171 exposure for 84 days elicited inflammation and damage in the mouse liver, whereas 28-day exposure did not. Whole-genome DNA methylation sequencing disclosed substantial methylation alterations at the CG and non-CG sites of the liver DNA in mice exposed to E 171 for 84 days. Mechanistic analysis of the DNA methylation alterations indicated that ferroptosis contributed to the liver toxicity induced by E 171. E 171-induced DNA methylation changes triggered NCOA4-mediated ferritinophagy, attenuated the protein levels of GPX4, FTH1, and FTL in the liver, and thereby caused ferroptosis. Long-term oral exposure to E 171 triggers hepatotoxicity and induces methylation changes in both CG and non-CG sites of liver DNA. These epigenetic alterations activate ferroptosis in the liver through NCOA4-mediated ferritinophagy, highlighting the role of DNA methylation and ferroptosis in the potential toxicity caused by E 171 in vivo.
继欧洲食品安全局宣布食品添加剂二氧化钛（E 171）对人类食用不安全，以及欧盟委员会随后颁布禁令之后，人们对 E 171 对人体重要器官构成的潜在风险的担忧进一步加剧。肝脏是食品级纳米粒子代谢的主要器官。越来越多的研究发现，表观遗传变化可能在纳米材料诱导的肝毒性中发挥重要作用。然而，E 171 对肝脏的深远影响，尤其是在表观遗传学水平上的影响，在很大程度上仍然未知。小鼠口服暴露于与人类相关剂量的两种混合在食物中的 E 171，为期 28 天和/或 84 天。进行常规毒理学和全 DNA 甲基化分析，以评估 E 171 诱导的肝毒性和表观遗传学变化。全基因组亚硫酸氢盐测序和进一步的铁突变蛋白检测用于揭示 E 171 诱导的肝脏甲基化特征变化和毒性机制。暴露于 E 171 28 天和/或 84 天会导致小鼠肝脏中 DNA 甲基化和羟甲基化的整体降低。接触 E 171 84 天会引起小鼠肝脏炎症和损伤，而接触 28 天则不会。全基因组 DNA 甲基化测序显示，暴露于 E 171 84 天的小鼠肝脏 DNA 的 CG 和非 CG 位点发生了重大的甲基化改变。对 DNA 甲基化改变的机理分析表明，铁突变是 E 171 诱导肝脏毒性的原因之一。E 171 诱导的 DNA 甲基化变化引发了 NCOA4 介导的铁蛋白吞噬作用，降低了肝脏中 GPX4、FTH1 和 FTL 的蛋白水平，从而导致了铁变态反应。长期口服 E 171 会引发肝中毒，并诱导肝脏 DNA 的 CG 和非 CG 位点发生甲基化变化。这些表观遗传学改变通过 NCOA4 介导的嗜铁蛋白激活了肝脏中的嗜铁细胞增多症，突出了 DNA 甲基化和嗜铁细胞增多症在 E 171 在体内引起的潜在毒性中的作用。
{"title":"Genome-wide DNA methylation sequencing reveals the involvement of ferroptosis in hepatotoxicity induced by dietary exposure to food-grade titanium dioxide","authors":"Jiaxin Shang, Jun Yan, He Lou, Rongshang Shou, Yingqi Zhan, Xiaoyan Lu, Xiaohui Fan","doi":"10.1186/s12989-024-00598-2","DOIUrl":"https://doi.org/10.1186/s12989-024-00598-2","url":null,"abstract":"Following the announcement by the European Food Safety Authority that the food additive titanium dioxide (E 171) is unsafe for human consumption, and the subsequent ban by the European Commission, concerns have intensified over the potential risks E 171 poses to human vital organs. The liver is the main organ for food-grade nanoparticle metabolism. It is increasingly being found that epigenetic changes may play an important role in nanomaterial-induced hepatotoxicity. However, the profound effects of E 171 on the liver, especially at the epigenetic level, remain largely unknown. Mice were exposed orally to human-relevant doses of two types of E 171 mixed in diet for 28 and/or 84 days. Conventional toxicology and global DNA methylation analyses were performed to assess E 171-induced hepatotoxicity and epigenetic changes. Whole genome bisulfite sequencing and further ferroptosis protein detection were used to reveal E 171-induced changes in liver methylation profiles and toxic mechanisms. Exposed to E 171 for 28 and/or 84 days resulted in reduced global DNA methylation and hydroxymethylation in the liver of mice. E 171 exposure for 84 days elicited inflammation and damage in the mouse liver, whereas 28-day exposure did not. Whole-genome DNA methylation sequencing disclosed substantial methylation alterations at the CG and non-CG sites of the liver DNA in mice exposed to E 171 for 84 days. Mechanistic analysis of the DNA methylation alterations indicated that ferroptosis contributed to the liver toxicity induced by E 171. E 171-induced DNA methylation changes triggered NCOA4-mediated ferritinophagy, attenuated the protein levels of GPX4, FTH1, and FTL in the liver, and thereby caused ferroptosis. Long-term oral exposure to E 171 triggers hepatotoxicity and induces methylation changes in both CG and non-CG sites of liver DNA. These epigenetic alterations activate ferroptosis in the liver through NCOA4-mediated ferritinophagy, highlighting the role of DNA methylation and ferroptosis in the potential toxicity caused by E 171 in vivo.","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":"214 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142259927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Microplastics (MPs), a brand-new class of worldwide environmental pollutant, have received a lot of attention. MPs are consumed by both humans and animals through water, food chain and other ways, which may cause potential health risks. However, the effects of MPs on embryonic development, especially placental function, and its related mechanisms still need to be further studied. We investigated the impact on fetal development and placental physiological function of pregnant mice by consecutive gavages of MPs at 0, 25, 50, 100 mg/kg body weight during gestational days (GDs 0–14). The results showed that continuous exposure to high concentrations of MP significantly reduced daily weight gain and impaired reproductive performance of pregnant mice. In addition, MPs could significantly induce oxidative stress and placental dysfunction in pregnant mice. On the other hand, MPs exposure significantly decreased placental barrier function and induced placental inflammation. Specifically, MPs treatment significantly reduced the expression of tight junction proteins in placentas, accompanied by inflammatory cell infiltration and increased mRNA levels of pro-inflammatory cytokines and chemokines in placentas. Finally, we found that MPs induced placental apoptosis and endoplasmic reticulum (ER) stress through the GRP78/IRE1α/JNK axis, leading to placental dysfunction and decreased reproductive performance in pregnant mice. We revealed for the first time that the effects of MPs on placental dysfunction in pregnant animals. Blocking the targets of MPs mediated ER stress will provide potential therapeutic ideas for the toxic effects of MPs on maternal pregnancy.
{"title":"Microplastics caused embryonic growth retardation and placental dysfunction in pregnant mice by activating GRP78/IRE1α/JNK axis induced apoptosis and endoplasmic reticulum stress","authors":"Jun Bai, Yuzeng Wang, Siwei Deng, Ying Yang, Sheng Chen, Zhenlong Wu","doi":"10.1186/s12989-024-00595-5","DOIUrl":"https://doi.org/10.1186/s12989-024-00595-5","url":null,"abstract":"Microplastics (MPs), a brand-new class of worldwide environmental pollutant, have received a lot of attention. MPs are consumed by both humans and animals through water, food chain and other ways, which may cause potential health risks. However, the effects of MPs on embryonic development, especially placental function, and its related mechanisms still need to be further studied. We investigated the impact on fetal development and placental physiological function of pregnant mice by consecutive gavages of MPs at 0, 25, 50, 100 mg/kg body weight during gestational days (GDs 0–14). The results showed that continuous exposure to high concentrations of MP significantly reduced daily weight gain and impaired reproductive performance of pregnant mice. In addition, MPs could significantly induce oxidative stress and placental dysfunction in pregnant mice. On the other hand, MPs exposure significantly decreased placental barrier function and induced placental inflammation. Specifically, MPs treatment significantly reduced the expression of tight junction proteins in placentas, accompanied by inflammatory cell infiltration and increased mRNA levels of pro-inflammatory cytokines and chemokines in placentas. Finally, we found that MPs induced placental apoptosis and endoplasmic reticulum (ER) stress through the GRP78/IRE1α/JNK axis, leading to placental dysfunction and decreased reproductive performance in pregnant mice. We revealed for the first time that the effects of MPs on placental dysfunction in pregnant animals. Blocking the targets of MPs mediated ER stress will provide potential therapeutic ideas for the toxic effects of MPs on maternal pregnancy.","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":"58 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142192870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Atmospheric particulate matter (PM) exposure-induced neuroinflammation is critical in mediating nervous system impairment. However, effective intervention is yet to be developed. In this study, we examine the effect of β-nicotinamide mononucleotide (NMN) supplementation on nervous system damage upon PM exposure and the mechanism of spatial regulation of lipid metabolism. 120 C57BL/6 male mice were exposed to real ambient PM for 11 days (subacute) or 16 weeks (sub-chronic). NMN supplementation boosted the level of nicotinamide adenine dinucleotide (NAD+) in the mouse brain by 2.04 times. This augmentation effectively reduced neuroinflammation, as evidenced by a marked decrease in activated microglia levels across various brain regions, ranging from 29.29 to 85.96%. Whole brain lipidomics analysis revealed that NMN intervention resulted in an less increased levels of ceramide (Cer) and lysophospholipid in the brain following subacute PM exposure, and reversed triglyceride (TG) and glycerophospholipids (GP) following sub-chronic PM exposure, which conferred mice with anti-neuroinflammation response, improved immune function, and enhanced membrane stability. In addition, we demonstrated that the hippocampus and hypothalamus might be the most sensitive brain regions in response to PM exposure and NMN supplementation. Particularly, the alteration of TG (60:10, 56:2, 60:7), diacylglycerol (DG, 42:6), and lysophosphatidylcholine (LPC, 18:3) are the most profound, which correlated with the changes in functional annotation and perturbation of pathways including oxidative stress, inflammation, and membrane instability unveiled by spatial transcriptomic analysis. This study demonstrates that NMN intervention effectively reduces neuroinflammation in the hippocampus and hypothalamus after PM exposure by modulating spatial lipid metabolism. Strategies targeting the improvement of lipid homeostasis may provide significant protection against brain injury associated with air pollutant exposure.
{"title":"Spatial regulation of NMN supplementation on brain lipid metabolism upon subacute and sub-chronic PM exposure in C57BL/6 mice","authors":"Yue Jiang, Fang Li, Lizhu Ye, Rui Zhang, Shen Chen, Hui Peng, Haiyan Zhang, Daochuan Li, Liping Chen, Xiaowen Zeng, Guanghui Dong, Wei Xu, Chunyang Liao, Rong Zhang, Qian Luo, Wen Chen","doi":"10.1186/s12989-024-00597-3","DOIUrl":"https://doi.org/10.1186/s12989-024-00597-3","url":null,"abstract":"Atmospheric particulate matter (PM) exposure-induced neuroinflammation is critical in mediating nervous system impairment. However, effective intervention is yet to be developed. In this study, we examine the effect of β-nicotinamide mononucleotide (NMN) supplementation on nervous system damage upon PM exposure and the mechanism of spatial regulation of lipid metabolism. 120 C57BL/6 male mice were exposed to real ambient PM for 11 days (subacute) or 16 weeks (sub-chronic). NMN supplementation boosted the level of nicotinamide adenine dinucleotide (NAD+) in the mouse brain by 2.04 times. This augmentation effectively reduced neuroinflammation, as evidenced by a marked decrease in activated microglia levels across various brain regions, ranging from 29.29 to 85.96%. Whole brain lipidomics analysis revealed that NMN intervention resulted in an less increased levels of ceramide (Cer) and lysophospholipid in the brain following subacute PM exposure, and reversed triglyceride (TG) and glycerophospholipids (GP) following sub-chronic PM exposure, which conferred mice with anti-neuroinflammation response, improved immune function, and enhanced membrane stability. In addition, we demonstrated that the hippocampus and hypothalamus might be the most sensitive brain regions in response to PM exposure and NMN supplementation. Particularly, the alteration of TG (60:10, 56:2, 60:7), diacylglycerol (DG, 42:6), and lysophosphatidylcholine (LPC, 18:3) are the most profound, which correlated with the changes in functional annotation and perturbation of pathways including oxidative stress, inflammation, and membrane instability unveiled by spatial transcriptomic analysis. This study demonstrates that NMN intervention effectively reduces neuroinflammation in the hippocampus and hypothalamus after PM exposure by modulating spatial lipid metabolism. Strategies targeting the improvement of lipid homeostasis may provide significant protection against brain injury associated with air pollutant exposure.","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":"2012 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142192871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-21DOI: 10.1186/s12989-024-00596-4
Yunxiao Yang, Feng Zhang, Zhili Jiang, Zhiyong Du, Sheng Liu, Ming Zhang, Yanyan Jin, Yanwen Qin, Xiubin Yang, Chenggang Wang, Hai Gao
Background: Microplastics, widely present in the environment, are implicated in disease pathogenesis through oxidative stress and immune modulation. Prevailing research, primarily based on animal and cell studies, falls short in elucidating microplastics' impact on human cardiovascular health. This cross-sectional study detected blood microplastic concentrations in patients presenting with chest pain using pyrolysis-gas chromatography/mass spectrometry and evaluating inflammatory and immune markers through flow cytometry, to explore the potential effects of microplastic on acute coronary syndrome.
Results: The study included 101 participants, comprising 19 controls and 82 acute coronary syndrome cases. Notably, acute coronary syndrome patients exhibited elevated microplastic concentrations, with those suffering from acute myocardial infarction presenting higher loads compared to those with unstable angina. Furthermore, patients at intermediate to high risk of coronary artery disease displayed significantly higher microplastic accumulations than their low-risk counterparts. A significant relationship was observed between increased microplastic levels and enhanced IL-6 and IL-12p70 contents, alongside elevated B lymphocyte and natural killer cell counts.
Conclusion: These results suggest an association between microplastics and both vascular pathology complexity and immunoinflammatory response in acute coronary syndrome, underscoring the critical need for targeted research to delineate the mechanisms of this association.
Highlights: 1 Blood microplastic levels escalate from angiographic patency, to angina patients, peaking in myocardial infarction patients. 2 Microplastics in acute coronary syndrome patients are predominantly PE, followed by PVC, PS, and PP. 3 Microplastics may induce immune cell-associated inflammatory responses in acute coronary syndrome patients.
{"title":"Microplastics are associated with elevated atherosclerotic risk and increased vascular complexity in acute coronary syndrome patients.","authors":"Yunxiao Yang, Feng Zhang, Zhili Jiang, Zhiyong Du, Sheng Liu, Ming Zhang, Yanyan Jin, Yanwen Qin, Xiubin Yang, Chenggang Wang, Hai Gao","doi":"10.1186/s12989-024-00596-4","DOIUrl":"10.1186/s12989-024-00596-4","url":null,"abstract":"<p><strong>Background: </strong>Microplastics, widely present in the environment, are implicated in disease pathogenesis through oxidative stress and immune modulation. Prevailing research, primarily based on animal and cell studies, falls short in elucidating microplastics' impact on human cardiovascular health. This cross-sectional study detected blood microplastic concentrations in patients presenting with chest pain using pyrolysis-gas chromatography/mass spectrometry and evaluating inflammatory and immune markers through flow cytometry, to explore the potential effects of microplastic on acute coronary syndrome.</p><p><strong>Results: </strong>The study included 101 participants, comprising 19 controls and 82 acute coronary syndrome cases. Notably, acute coronary syndrome patients exhibited elevated microplastic concentrations, with those suffering from acute myocardial infarction presenting higher loads compared to those with unstable angina. Furthermore, patients at intermediate to high risk of coronary artery disease displayed significantly higher microplastic accumulations than their low-risk counterparts. A significant relationship was observed between increased microplastic levels and enhanced IL-6 and IL-12p70 contents, alongside elevated B lymphocyte and natural killer cell counts.</p><p><strong>Conclusion: </strong>These results suggest an association between microplastics and both vascular pathology complexity and immunoinflammatory response in acute coronary syndrome, underscoring the critical need for targeted research to delineate the mechanisms of this association.</p><p><strong>Highlights: </strong>1 Blood microplastic levels escalate from angiographic patency, to angina patients, peaking in myocardial infarction patients. 2 Microplastics in acute coronary syndrome patients are predominantly PE, followed by PVC, PS, and PP. 3 Microplastics may induce immune cell-associated inflammatory responses in acute coronary syndrome patients.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":"21 1","pages":"34"},"PeriodicalIF":7.2,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11337598/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142009236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-14DOI: 10.1186/s12989-024-00588-4
Ilse Gosens, Jordi Minnema, A John F Boere, Evert Duistermaat, Paul Fokkens, Janja Vidmar, Katrin Löschner, Bas Bokkers, Anna L Costa, Ruud J B Peters, Christiaan Delmaar, Flemming R Cassee
Background: Physiologically based kinetic models facilitate the safety assessment of inhaled engineered nanomaterials (ENMs). To develop these models, high quality datasets on well-characterized ENMs are needed. However, there are at present, several data gaps in the systemic availability of poorly soluble particles after inhalation. The aim of the present study was therefore to acquire two comparable datasets to parametrize a physiologically-based kinetic model.
Method: Rats were exposed to cerium dioxide (CeO2, 28.4 ± 10.4 nm) and titanium dioxide (TiO2, 21.6 ± 1.5 nm) ENMs in a single nose-only exposure to 20 mg/m3 or a repeated exposure of 2 × 5 days to 5 mg/m3. Different dose levels were obtained by varying the exposure time for 30 min, 2 or 6 h per day. The content of cerium or titanium in three compartments of the lung (tissue, epithelial lining fluid and freely moving cells), mediastinal lymph nodes, liver, spleen, kidney, blood and excreta was measured by Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) at various time points post-exposure. As biodistribution is best studied at sub-toxic dose levels, lactate dehydrogenase (LDH), total protein, total cell numbers and differential cell counts were determined in bronchoalveolar lavage fluid (BALF).
Results: Although similar lung deposited doses were obtained for both materials, exposure to CeO2 induced persistent inflammation indicated by neutrophil granulocytes influx and exhibited an increased lung elimination half-time, while exposure to TiO2 did not. The lavaged lung tissue contained the highest metal concentration compared to the lavage fluid and cells in the lavage fluid for both materials. Increased cerium concentrations above control levels in secondary organs such as lymph nodes, liver, spleen, kidney, urine and faeces were detected, while for titanium this was found in lymph nodes and liver after repeated exposure and in blood and faeces after a single exposure.
Conclusion: We have provided insight in the distribution kinetics of these two ENMs based on experimental data and modelling. The study design allows extrapolation at different dose-levels and study durations. Despite equal dose levels of both ENMs, we observed different distribution patterns, that, in part may be explained by subtle differences in biological responses in the lung.
{"title":"Biodistribution of cerium dioxide and titanium dioxide nanomaterials in rats after single and repeated inhalation exposures.","authors":"Ilse Gosens, Jordi Minnema, A John F Boere, Evert Duistermaat, Paul Fokkens, Janja Vidmar, Katrin Löschner, Bas Bokkers, Anna L Costa, Ruud J B Peters, Christiaan Delmaar, Flemming R Cassee","doi":"10.1186/s12989-024-00588-4","DOIUrl":"10.1186/s12989-024-00588-4","url":null,"abstract":"<p><strong>Background: </strong>Physiologically based kinetic models facilitate the safety assessment of inhaled engineered nanomaterials (ENMs). To develop these models, high quality datasets on well-characterized ENMs are needed. However, there are at present, several data gaps in the systemic availability of poorly soluble particles after inhalation. The aim of the present study was therefore to acquire two comparable datasets to parametrize a physiologically-based kinetic model.</p><p><strong>Method: </strong>Rats were exposed to cerium dioxide (CeO<sub>2</sub>, 28.4 ± 10.4 nm) and titanium dioxide (TiO<sub>2,</sub> 21.6 ± 1.5 nm) ENMs in a single nose-only exposure to 20 mg/m<sup>3</sup> or a repeated exposure of 2 × 5 days to 5 mg/m<sup>3</sup>. Different dose levels were obtained by varying the exposure time for 30 min, 2 or 6 h per day. The content of cerium or titanium in three compartments of the lung (tissue, epithelial lining fluid and freely moving cells), mediastinal lymph nodes, liver, spleen, kidney, blood and excreta was measured by Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) at various time points post-exposure. As biodistribution is best studied at sub-toxic dose levels, lactate dehydrogenase (LDH), total protein, total cell numbers and differential cell counts were determined in bronchoalveolar lavage fluid (BALF).</p><p><strong>Results: </strong>Although similar lung deposited doses were obtained for both materials, exposure to CeO<sub>2</sub> induced persistent inflammation indicated by neutrophil granulocytes influx and exhibited an increased lung elimination half-time, while exposure to TiO<sub>2</sub> did not. The lavaged lung tissue contained the highest metal concentration compared to the lavage fluid and cells in the lavage fluid for both materials. Increased cerium concentrations above control levels in secondary organs such as lymph nodes, liver, spleen, kidney, urine and faeces were detected, while for titanium this was found in lymph nodes and liver after repeated exposure and in blood and faeces after a single exposure.</p><p><strong>Conclusion: </strong>We have provided insight in the distribution kinetics of these two ENMs based on experimental data and modelling. The study design allows extrapolation at different dose-levels and study durations. Despite equal dose levels of both ENMs, we observed different distribution patterns, that, in part may be explained by subtle differences in biological responses in the lung.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":"21 1","pages":"33"},"PeriodicalIF":7.2,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11323389/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141982934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-12DOI: 10.1186/s12989-024-00591-9
Dong-Keun Lee, Gyuri Kim, Muthuchamy Maruthupandy, Kyuhong Lee, Wan-Seob Cho
Alveolar macrophages (AMs) have been predicted to affect the pulmonary clearance of nanomaterials; however, their qualitative and quantitative roles are poorly understood. In this study, carbon black nanoparticles (CBNPs) were instilled into the lungs of Wistar rats at 30, 100, and 300 µg/rat. The concentrations of particles in organs, including the lung, lung-associated lymph nodes (LALN), liver, spleen, and kidney, were evaluated at days 0 (immediately after instillation), 1, 7, 28, 60, and 90 post-instillation. The results indicated a multimodal pulmonary clearance pattern for CBNPs: slow clearance until day 28, fast clearance from days 28 to 60, and slow clearance from days 60 to 90. To determine the mechanism of this unique clearance pattern, CBNPs were instilled into AM-depleted rats using clodronate liposomes (CLO). At 28 days after instillation, the CBNP levels in the lungs treated with CLO showed about 31% higher reduction than in normal rats. In addition, the concentration of CBNPs in LALN treated with CLO significantly increased on day 28, whereas in normal rats, no detectable levels were observed. This result highlights that the prolonged retention of poorly soluble NPs in the lung until day 28 is mediated by the phagocytosis of AMs, and the fast clearance between days 28–60 is due to the turnover time of AMs, estimated around 1–2 months after birth. Similarly, new generations of AMs mediate the slow phase between days 60 and 90. However, further studies are needed to understand the multimodal clearance mechanism and the modulation of pulmonary clearance of poorly soluble NPs.
{"title":"Multimodal pulmonary clearance kinetics of carbon black nanoparticles deposited in the lungs of rats: the role of alveolar macrophages","authors":"Dong-Keun Lee, Gyuri Kim, Muthuchamy Maruthupandy, Kyuhong Lee, Wan-Seob Cho","doi":"10.1186/s12989-024-00591-9","DOIUrl":"https://doi.org/10.1186/s12989-024-00591-9","url":null,"abstract":"Alveolar macrophages (AMs) have been predicted to affect the pulmonary clearance of nanomaterials; however, their qualitative and quantitative roles are poorly understood. In this study, carbon black nanoparticles (CBNPs) were instilled into the lungs of Wistar rats at 30, 100, and 300 µg/rat. The concentrations of particles in organs, including the lung, lung-associated lymph nodes (LALN), liver, spleen, and kidney, were evaluated at days 0 (immediately after instillation), 1, 7, 28, 60, and 90 post-instillation. The results indicated a multimodal pulmonary clearance pattern for CBNPs: slow clearance until day 28, fast clearance from days 28 to 60, and slow clearance from days 60 to 90. To determine the mechanism of this unique clearance pattern, CBNPs were instilled into AM-depleted rats using clodronate liposomes (CLO). At 28 days after instillation, the CBNP levels in the lungs treated with CLO showed about 31% higher reduction than in normal rats. In addition, the concentration of CBNPs in LALN treated with CLO significantly increased on day 28, whereas in normal rats, no detectable levels were observed. This result highlights that the prolonged retention of poorly soluble NPs in the lung until day 28 is mediated by the phagocytosis of AMs, and the fast clearance between days 28–60 is due to the turnover time of AMs, estimated around 1–2 months after birth. Similarly, new generations of AMs mediate the slow phase between days 60 and 90. However, further studies are needed to understand the multimodal clearance mechanism and the modulation of pulmonary clearance of poorly soluble NPs.","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":"303 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141930748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号