Inhalation Toxicology最新文献

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Co-exposure of peptidoglycan and heat-inactivated Asian sand dust exacerbates ovalbumin-induced allergic airway inflammation in mice 肽聚糖和热灭活的亚洲沙尘的共同暴露加剧了卵清蛋白诱导的小鼠过敏性气道炎症
IF 2.1 4区 医学
Inhalation Toxicology Pub Date : 2022-06-13 DOI: 10.1080/08958378.2022.2086650
K. Sadakane, T. Ichinose, T. Maki, M. Nishikawa
{"title":"Co-exposure of peptidoglycan and heat-inactivated Asian sand dust exacerbates ovalbumin-induced allergic airway inflammation in mice","authors":"K. Sadakane, T. Ichinose, T. Maki, M. Nishikawa","doi":"10.1080/08958378.2022.2086650","DOIUrl":"https://doi.org/10.1080/08958378.2022.2086650","url":null,"abstract":"Abstract Aims Asian sand dust (ASD) comprises soil particles, microorganisms, and various chemical components. We examined whether peptidoglycan (PGN), a structural cell wall component of Gram-positive bacteria, exacerbates ASD-induced allergic airway inflammation in mice. Methods The ASD (median diameter ∼4 µm) used was a certified reference material from the National Institute for Environmental Studies in Japan, derived from Gobi Desert surface soil collected in 2011. BALB/c mice were intratracheally exposed to PGN, heat-inactivated ASD (H-ASD), and ovalbumin (OVA), individually and in combination. Twenty-four hours after the final intratracheal administration, bronchoalveolar lavage fluid (BALF) and serum samples were collected. Inflammatory cell count, cytokine levels in the BALF, OVA-specific immunoglobulin levels in the serum, and pathological changes in the lungs were analyzed. Results and Discussion After OVA + PGN + H-ASD treatment, the number of eosinophils, neutrophils, and macrophages in the BALF and of eosinophils in the lung tissue was significantly higher than that after OVA + PGN or OVA + H-ASD treatment. Moreover, levels of chemokines and cytokines associated with eosinophil recruitment and activation were significantly higher in the BALF of this group than in that of the OVA + PGN group, and tended to be higher than those in the OVA + H-ASD group. Pathological changes in the lungs were most severe in mice treated with OVA + PGN + H-ASD. Conclusions Our results indicate that PGN is involved in the exacerbation of ASD-induced allergic airway inflammation in mice. Thus, inhalation of ASD containing Gram-positive bacteria may trigger allergic bronchial asthma.","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":"34 1","pages":"231 - 243"},"PeriodicalIF":2.1,"publicationDate":"2022-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43858169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Liver transcriptome analysis reveals biological pathways and transcription factors in response to high ammonia exposure 肝脏转录组分析揭示了高氨暴露的生物学途径和转录因子
IF 2.1 4区 医学
Inhalation Toxicology Pub Date : 2022-06-01 DOI: 10.1080/08958378.2022.2083275
Daojie Li, Shu-Wei Chen, Chun Liu, Baoxin Wei, Xiaoping Li
{"title":"Liver transcriptome analysis reveals biological pathways and transcription factors in response to high ammonia exposure","authors":"Daojie Li, Shu-Wei Chen, Chun Liu, Baoxin Wei, Xiaoping Li","doi":"10.1080/08958378.2022.2083275","DOIUrl":"https://doi.org/10.1080/08958378.2022.2083275","url":null,"abstract":"Abstract Aim: Ammonia is a toxic gas that not only causes environmental pollution, but also is harmful to human health after inhalation. Liver is an important detoxification organ that can convert external or metabolized toxic substances into nontoxic substances. However, the toxic effects of ammonia exposure on livers have not been well studied. Method: In this study, pigs were used as an animal model and were exposed to 80 ppm ammonia (8 h during 12 days), and then, RNA-seq were conducted to explore the key genes in response to high ammonia exposure in livers. Result: Gene set enrichment analysis (GSEA) showed that the genes associated with hypoxia, inflammatory response, and apoptosis were up-regulated in the ammonia group, but the genes associated with DNA replication, linoleic acid metabolism, and glycolysis were down-regulated. Totally, 556 differentially expressed genes (DEGs) including 54 genes that encode the transcription factors (TFs) were identified between the exposure and control groups. GO and KEGG pathway analysis suggested that these DEGs were involved in inflammatory response, oxidative stress, apoptosis, immune, and cell cycle. Furthermore, the TF-target interaction analysis showed that FOS, HIF-1α, JUNB, ATF3, REL, and KLF4 were important TFs in regulating the hepatic gene expression in response to high ammonia exposure. Conclusion: Altogether, our findings not only presented a comprehensive mRNA transcriptome profile of liver after high ammonia exposure, but also found some key genes and TFs that could be used to investigate the toxicity mechanism of high ammonia on livers.","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":"34 1","pages":"219 - 229"},"PeriodicalIF":2.1,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48787087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
A filter-based system mimicking the particle deposition and penetration in human respiratory system for secondhand smoke generation and characterization 一种基于过滤器的系统,模拟人类呼吸系统中的颗粒沉积和渗透,用于二手烟的产生和表征
IF 2.1 4区 医学
Inhalation Toxicology Pub Date : 2022-05-18 DOI: 10.1080/08958378.2022.2075493
Weixing Hao, K. F. Kapiamba, Varuni Abhayaratne, S. Usman, Yue-Wern Huang, Yang Wang
{"title":"A filter-based system mimicking the particle deposition and penetration in human respiratory system for secondhand smoke generation and characterization","authors":"Weixing Hao, K. F. Kapiamba, Varuni Abhayaratne, S. Usman, Yue-Wern Huang, Yang Wang","doi":"10.1080/08958378.2022.2075493","DOIUrl":"https://doi.org/10.1080/08958378.2022.2075493","url":null,"abstract":"Abstract Introduction Secondhand smoke endangers both the environment and the health of nonsmokers. Due to the scarcity of repeatable data generated by human subjects, a system capable of generating representative secondhand smoke is essential for studying smoke properties. This work presents the design and validation of a filter-based system that could mimic the particle deposition and penetration in human respiratory system for secondhand smoke generation and characterization. Methods Guided by our study on characterizing size-dependent filtration efficiency of common materials, we identified three filter media that generate similar particle deposition efficiencies compared to different regions of the human respiratory system over a wide submicron size range. We demonstrated the performance of the proposed filter-based system using various operating conditions. Additionally, we compared the properties of secondhand smoke particles to those of primary smoke particles. Results The difference in aerosol deposition efficiencies between the filter-based system and the International Commission on Radiological Protection (ICRP) model was less than 10% in the size range of 30 to 500 nm. High concentrations of metals were detected in the secondhand smoke. The contents of Ni and Cr generated from the secondhand electronic cigarettes are at least 20 and 5 times above the regulated daily maximum intake amount. Conclusion Given the agreement in aerosol respiratory deposition between the filter-based system and the ICRP model, such a system can facilitate laboratory studies of secondhand smoke due to its simple structure, high repeatability, and ease of control while remaining free of human subjects.","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":"34 1","pages":"189 - 199"},"PeriodicalIF":2.1,"publicationDate":"2022-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47313779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 2
Successful treatment of pulmonary injury due to nitrogen oxide exposure with extracorporeal membrane oxygenation: a report of two cases and literature review 体外膜氧合成功治疗氧化氮暴露肺损伤2例报告并文献复习
IF 2.1 4区 医学
Inhalation Toxicology Pub Date : 2022-05-03 DOI: 10.1080/08958378.2022.2070690
Jian Liu, Yong-Quan Dong, Xuejie Li, Weifang Wu
{"title":"Successful treatment of pulmonary injury due to nitrogen oxide exposure with extracorporeal membrane oxygenation: a report of two cases and literature review","authors":"Jian Liu, Yong-Quan Dong, Xuejie Li, Weifang Wu","doi":"10.1080/08958378.2022.2070690","DOIUrl":"https://doi.org/10.1080/08958378.2022.2070690","url":null,"abstract":"Abstract Background: Severe nitrogen oxide poisoning can lead to life-threatening pulmonary injury. Methods: we report two cases of severe nitrogen-oxide-induced hypoxia treated with veno-venous extracorporeal membrane oxygenation (ECMO). After exposure, the conditions of both patients continued to deteriorate despite maximal mechanical ventilation with a fraction of inspired oxygen of 100%; therefore, we started veno-venous ECMO. The times from presentation to the initiation of ECMO in the two patients were 1 and 2 days. The hypoxemia and respiratory failure improved quickly after ECMO support. Results: The patients were discharged without complications. The durations of ECMO for the two patients were 5 and 6 days. Conclusion: This report describes how early ECMO support was used to treat potentially fatal pulmonary injury after exposure to nitrogen oxide. The duration of the ECMO run is a critical determinant of patient survival.","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":"34 1","pages":"171 - 174"},"PeriodicalIF":2.1,"publicationDate":"2022-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43256212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A controlled chamber study of effects of exposure to diesel exhaust particles and noise on heart rate variability and endothelial function 暴露于柴油废气颗粒物和噪声对心率变异性和内皮功能影响的对照室研究
IF 2.1 4区 医学
Inhalation Toxicology Pub Date : 2022-04-27 DOI: 10.1080/08958378.2022.2065388
L. Stockfelt, Yiyi Xu, A. Gudmundsson, J. Rissler, C. Isaxon, J. Brunskog, J. Pagels, P. Nilsson, M. Berglund, L. Barregard, M. Bohgard, M. Albin, I. Hagerman, A. Wierzbicka
{"title":"A controlled chamber study of effects of exposure to diesel exhaust particles and noise on heart rate variability and endothelial function","authors":"L. Stockfelt, Yiyi Xu, A. Gudmundsson, J. Rissler, C. Isaxon, J. Brunskog, J. Pagels, P. Nilsson, M. Berglund, L. Barregard, M. Bohgard, M. Albin, I. Hagerman, A. Wierzbicka","doi":"10.1080/08958378.2022.2065388","DOIUrl":"https://doi.org/10.1080/08958378.2022.2065388","url":null,"abstract":"Abstract Background Adverse cardiovascular effects are associated with both diesel exhaust and road traffic noise, but these exposures are hard to disentangle epidemiologically. We used an experimental setup to evaluate the impact of diesel exhaust particles and traffic noise, alone and combined, on intermediary outcomes related to the autonomic nervous system and increased cardiovascular risk. Methods In a controlled chamber 18 healthy adults were exposed to four scenarios in a randomized cross-over fashion. Each exposure scenario consisted of either filtered (clean) air or diesel engine exhaust (particle mass concentrations around 300 µg/m3), and either low (46 dB(A)) or high (75 dB(A)) levels of traffic noise for 3 h at rest. ECG was recorded for 10-min periods before and during each exposure type, and frequency-domain heart rate variability (HRV) computed. Endothelial dysfunction and arterial stiffness were assessed after each exposure using EndoPAT 2000. Results Compared to control exposure, HRV in the high frequency band decreased during exposure to diesel exhaust, both alone and combined with noise, but not during noise exposure only. These differences were more pronounced in women. We observed no synergistic effects of combined exposure, and no significant differences between exposure scenarios for other HRV indices, endothelial function or arterial stiffness. Conclusion Three-hour exposure to diesel exhaust, but not noise, was associated with decreased HRV in the high frequency band. This indicates activation of irritant receptor-mediated autonomic reflexes, a possible mechanism for the cardiovascular risks of diesel exposure. There was no effect on endothelial dysfunction or arterial stiffness after exposure.","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":"34 1","pages":"159 - 170"},"PeriodicalIF":2.1,"publicationDate":"2022-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42767307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Ammonia exposure by intratracheal instillation causes severe and deteriorating lung injury and vascular effects in mice 气管内滴注氨暴露导致小鼠严重和恶化的肺损伤和血管影响
IF 2.1 4区 医学
Inhalation Toxicology Pub Date : 2022-04-22 DOI: 10.1080/08958378.2022.2064566
L. Elfsmark, L. Ågren, C. Akfur, S. Jonasson
{"title":"Ammonia exposure by intratracheal instillation causes severe and deteriorating lung injury and vascular effects in mice","authors":"L. Elfsmark, L. Ågren, C. Akfur, S. Jonasson","doi":"10.1080/08958378.2022.2064566","DOIUrl":"https://doi.org/10.1080/08958378.2022.2064566","url":null,"abstract":"Abstract Objective Ammonia (NH3) is a corrosive alkaline gas that can cause life-threatening injuries by inhalation. The aim was to establish a disease model for NH3-induced injuries similar to acute lung injury (ALI) described in exposed humans and investigate the progression of lung damage, respiratory dysfunction and evaluate biomarkers for ALI and inflammation over time. Methods Female BALB/c mice were exposed to an NH3 dose of 91.0 mg/kg·bw using intratracheal instillation and the pathological changes were followed for up to 7 days. Results NH3 instillation resulted in the loss of body weight along with a significant increase in pro-inflammatory mediators in both bronchoalveolar lavage fluid (e.g. IL-1β, IL-6, KC, MMP-9, SP-D) and blood (e.g. IL-6, Fibrinogen, PAI-1, PF4/CXCL4, SP-D), neutrophilic lung inflammation, alveolar damage, increased peripheral airway resistance and methacholine-induced airway hyperresponsiveness compared to controls at 20 h. On day 7 after exposure, deteriorating pathological changes such as increased macrophage lung infiltration, heart weights, lung hemorrhages and coagulation abnormalities (elevated plasma levels of PAI-1, fibrinogen, endothelin and thrombomodulin) were observed but no increase in lung collagen. Some of the analyzed blood biomarkers (e.g. RAGE, IL-1β) were unaffected despite severe ALI and may not be significant for NH3-induced damages. Conclusions NH3 induces severe acute lung injuries that deteriorate over time and biomarkers in lungs and blood that are similar to those found in humans. Therefore, this model has potential use for developing diagnostic tools for NH3-induced ALI and for finding new therapeutic treatments, since no specific antidote has been identified yet.","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":"34 1","pages":"145 - 158"},"PeriodicalIF":2.1,"publicationDate":"2022-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46256945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A procedure to detect and identify specific chemicals of potential inhalation toxicity concern in aerosols 检测和识别气溶胶中潜在吸入毒性的特定化学物质的程序
IF 2.1 4区 医学
Inhalation Toxicology Pub Date : 2022-03-28 DOI: 10.1080/08958378.2022.2051646
Theodore P. Klupinski, R. Moyer, Po-Hsu Allen Chen, E. Strozier, Stephanie Buehler, D. Friedenberg, Bartosz Koszowski
{"title":"A procedure to detect and identify specific chemicals of potential inhalation toxicity concern in aerosols","authors":"Theodore P. Klupinski, R. Moyer, Po-Hsu Allen Chen, E. Strozier, Stephanie Buehler, D. Friedenberg, Bartosz Koszowski","doi":"10.1080/08958378.2022.2051646","DOIUrl":"https://doi.org/10.1080/08958378.2022.2051646","url":null,"abstract":"Abstract Objective Understanding the potential inhalation toxicity of poorly characterized aerosols is challenging both because aerosols may contain numerous chemicals and because it is difficult to predict which chemicals may present significant inhalation toxicity concerns at the observed levels. We have developed a novel systematic procedure to address these challenges through non-targeted chemical analysis by two-dimensional gas chromatography–time-of-flight mass spectrometry (GC × GC-TOFMS) and assessment of the results using publicly available toxicity data to prioritize the tentatively identified detected chemicals according to potential inhalation toxicity. Materials and Methods The procedure involves non-targeted chemical analysis of aerosol samples utilizing GC × GC-TOFMS, which is selected because it is an effective technique for detecting chemicals in complex samples and assigning tentative identities according to the mass spectra. For data evaluation, existing toxicity data (e.g. from the U.S. Environmental Protection Agency CompTox Chemicals Dashboard) are used to calculate multiple toxicity metrics that can be compared among the tentatively identified chemicals. These metrics include hazard quotient, incremental lifetime cancer risk, and metrics analogous to hazard quotient that we designated as exposure–(toxicology endpoint) ratios. Results and Discussion We demonstrated the utility of our procedure by detecting, identifying, and prioritizing specific chemicals of potential inhalation toxicity concern in the mainstream smoke generated from the machine-smoking of marijuana blunts. Conclusion By designing a systematic approach for detecting and identifying numerous chemicals in complex aerosol samples and prioritizing the chemicals in relation to different inhalation toxicology endpoints, we have developed an effective approach to elucidate the potential inhalation toxicity of aerosols.","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":"34 1","pages":"120 - 134"},"PeriodicalIF":2.1,"publicationDate":"2022-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41527224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Updated Italian cohort data continues to confirm lack of mesothelioma risk in pooled cohort of international cosmetic talc miners and millers 最新的意大利队列数据继续证实,国际化妆品滑石矿矿工和磨粉工人的队列中没有间皮瘤风险
IF 2.1 4区 医学
Inhalation Toxicology Pub Date : 2022-03-26 DOI: 10.1080/08958378.2022.2053251
A. Ierardi, Elizabeth A. Best, G. Marsh
{"title":"Updated Italian cohort data continues to confirm lack of mesothelioma risk in pooled cohort of international cosmetic talc miners and millers","authors":"A. Ierardi, Elizabeth A. Best, G. Marsh","doi":"10.1080/08958378.2022.2053251","DOIUrl":"https://doi.org/10.1080/08958378.2022.2053251","url":null,"abstract":"Abstract Objectives To assess potential mesothelioma risk following inhalation of cosmetic talc, we updated previous iterations of a pooled cohort analysis, post-study statistical power analysis, and confidence interval function analysis for a pooled cohort of international cosmetic talc miners/millers given new Italian cohort data. Methods Five cohorts of cosmetic talc miners/millers were pooled. Expected numbers of mesotheliomas for each cohort were reported by the original authors. We based our post-study statistical power analysis on an a priori one-sided significance level of 0.05, and exact Poisson and approximate distribution probabilities. To evaluate the confidence interval function for the observed pooled mesothelioma standardized mortality ratios (SMRs), we calculated the probability for the upper 100(1–2α)% confidence limit that equals various SMRs of interest. Results The pooled cohorts generated a total observation time of 135,524.38 person-years. Overall, 4.14 mesotheliomas were expected (mid-value estimate), though only one case of mesothelioma has been confirmed in the pooled cohort to date. We calculated 71% and 87% post-study power to detect a 2.5-fold or greater and a 3.0-fold or greater increase in mesothelioma, respectively. Our complimentary confidence interval function analysis demonstrated that the probability that the true mesothelioma SMR for the pooled cohort was at or above 2.0 or at or above 3.0 was 0.00235 and 0.00005, respectively. Conclusions Based on the updated results of our various analyses, the current epidemiological evidence from cosmetic talc miner/miller cohort studies continues to not support the hypothesis that the inhalation of cosmetic talc is associated with an increased risk of mesothelioma.","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":"34 1","pages":"135 - 144"},"PeriodicalIF":2.1,"publicationDate":"2022-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44772784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 6
Comparative pulmonary toxicities of lunar dusts and terrestrial dusts (TiO2 & SiO2) in rats and an assessment of the impact of particle-generated oxidants on the dusts’ toxicities 月球尘埃和陆地尘埃(TiO2和SiO2)对大鼠的肺部毒性比较以及颗粒产生的氧化剂对尘埃毒性影响的评估
IF 2.1 4区 医学
Inhalation Toxicology Pub Date : 2022-03-16 DOI: 10.1080/08958378.2022.2038736
C. Lam, V. Castranova, P. Zeidler-Erdely, R. Renne, Robert Hunter, R. McCluskey, R. R. Scully, W. T. Wallace, Ye Zhang, Valerie E. Ryder, B. Cooper, David McKay, R. McClellan, K. Driscoll, D. Gardner, M. Barger, T. Meighan, J. James
{"title":"Comparative pulmonary toxicities of lunar dusts and terrestrial dusts (TiO2 & SiO2) in rats and an assessment of the impact of particle-generated oxidants on the dusts’ toxicities","authors":"C. Lam, V. Castranova, P. Zeidler-Erdely, R. Renne, Robert Hunter, R. McCluskey, R. R. Scully, W. T. Wallace, Ye Zhang, Valerie E. Ryder, B. Cooper, David McKay, R. McClellan, K. Driscoll, D. Gardner, M. Barger, T. Meighan, J. James","doi":"10.1080/08958378.2022.2038736","DOIUrl":"https://doi.org/10.1080/08958378.2022.2038736","url":null,"abstract":"Abstract Humans will set foot on the Moon again soon. The lunar dust (LD) is potentially reactive and could pose an inhalation hazard to lunar explorers. We elucidated LD toxicity and investigated the toxicological impact of particle surface reactivity (SR) using three LDs, quartz, and TiO2. We first isolated the respirable-size-fraction of an Apollo-14 regolith and ground two coarser samples to produce fine LDs with increased SR. SR measurements of these five respirable-sized dusts, determined by their in-vitro ability to generate hydroxyl radicals (•OH), showed that ground LDs > unground LD ≥ TiO2 ≥ quartz. Rats were each intratracheally instilled with 0, 1, 2.5, or 7.5 mg of a test dust. Toxicity biomarkers and histopathology were assessed up to 13 weeks after the bolus instillation. All dusts caused dose-dependent-increases in pulmonary lesions and toxicity biomarkers. The three LDs, which possessed mineral compositions/properties similar to Arizona volcanic ash, were moderately toxic. Despite a 14-fold •OH difference among these three LDs, their toxicities were indistinguishable. Quartz produced the lowest •OH amount but showed the greatest toxicity. Our results showed no correlation between the toxicity of mineral dusts and their ability to generate free radicals. We also showed that the amounts of oxidants per neutrophil increased with doses, time and the cytotoxicity of the dusts in the lung, which supports our postulation that dust-elicited neutrophilia is the major persistent source of oxidative stress. These results and the discussion of the crucial roles of the short-lived, continuously replenished neutrophils in dust-induced pathogenesis are presented.","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":"34 1","pages":"51 - 67"},"PeriodicalIF":2.1,"publicationDate":"2022-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42816696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 3
Inhalation of PM2.5 from diesel exhaust promote impairment of mitochondrial bioenergetics and dysregulate mitochondrial quality in rat heart: implications in isoproterenol-induced myocardial infarction model 在异丙肾上腺素诱导的心肌梗死模型中,吸入柴油机尾气PM2.5可促进大鼠心脏线粒体生物能量学损伤和线粒体质量失调
IF 2.1 4区 医学
Inhalation Toxicology Pub Date : 2022-03-15 DOI: 10.1080/08958378.2022.2049931
B. Sivakumar, G. Kurian
{"title":"Inhalation of PM2.5 from diesel exhaust promote impairment of mitochondrial bioenergetics and dysregulate mitochondrial quality in rat heart: implications in isoproterenol-induced myocardial infarction model","authors":"B. Sivakumar, G. Kurian","doi":"10.1080/08958378.2022.2049931","DOIUrl":"https://doi.org/10.1080/08958378.2022.2049931","url":null,"abstract":"Abstract Aim: Ambient exposure of PM2.5 from diesel exhaust (termed as diesel particulate matter [DPM]) can induce cardiotoxicity that can be manifested into myocardial ischemia/infarction, where the survival depends on mitochondrial function. The mechanism for DPM-induced mitochondrial dysfunction is yet to be elucidated and the consequential impact of impaired mitochondria on the severity of myocardial infarction (MI) has not been established. Materials and methods: Female Wistar rats were exposed to DPM (0.5 mg/ml) for 3 h daily (to achieve a PM2.5 concentration of 250 µg/m3) for 21 d trailed by an induction of MI using isoproterenol (ISO). Conclusion: DPM exposure altered the basal ECG pattern and increased heart weight (HW) to body weight (BW) ratio from control. Loss of mitochondrial quality in the cardiac tissue was observed in DPM exposed animals, measured via declined ETC enzyme activity, reduced ATP levels, high oxidative stress, low mitochondrial copy number, and low expression of the mitochondrial genes involved in mitophagy (PINK and PARKIN) and mitochondrial fusion (MFN-1). Subsequent induction of MI in DPM exposed animals (DPM + ISO) further deteriorated the normal sinus rhythm, accompanied by elevated plasma CK and LDH level, increased myocardial caspase activity, downregulation of Peroxisome proliferator-activated receptor-gamma coactivator (PGC1-α), transcription factor A (TFAM), DNA polymerase subunit gamma (POLG), and other mitochondrial quality control genes. Based on these results, we conclude that DPM alters the electrophysiology and ultrastructure of the heart that aggravates the MI-induced cardiotoxicity, where the diminished mitochondrial quality can be the potential contributor.","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":"34 1","pages":"107 - 119"},"PeriodicalIF":2.1,"publicationDate":"2022-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43840208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 2
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