Journal of Applied Toxicology最新文献

{"title":"A Rapid Quantitative Assessment Method for Liver Damage Effects of Compounds Based on Zebrafish Liver Partition Area Ratio.","authors":"Jing Yang, Jingcheng Zhao, Te Zheng, Jiashuo Zhou, Huiwen Zhang, Yun Zhang","doi":"10.1002/jat.4726","DOIUrl":"10.1002/jat.4726","url":null,"abstract":"<p><p>Total liver area is a traditional indicator in evaluating compound liver damage with zebrafish models. However, in some experiments, compounds changed zebrafish liver morphology but total liver area showed no significant difference, indicating it is inaccurate for evaluating compound effects on zebrafish liver damage. Therefore, in this study, transgenic zebrafish Tg(l-fabp:EGFP) labeled with liver cells using green fluorescent protein was used to evaluate compound effects on liver by the liver partition area ratio. The coefficient of variation of the total liver area and the liver partition area ratio of normal zebrafish at different development stages was calculated to determine the precision and dispersion of the liver partition area ratio. Three known hepatotoxic compounds (water extract of psoralea, alcohol, and α-naphthalene isothiocyanate) were used to treat zebrafish, and liver partition area ratio was calculated and verified by liver tissue pathological sections. The Pearson correlation coefficient was used to analyze the correlation between the liver partition area ratio, total liver area, and alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Results showed significant difference in liver partition area ratio between hepatotoxic compound treated group and control group, and it could accurately reflect liver morphology changes. There was a strong correlation between liver partition area ratio and ALT and AST level, whereas that between total liver area and ALT and AST level was low. Therefore, the change in zebrafish liver partition area ratio can be an evaluation indicator for rapid assessment of compound effects on zebrafish liver function damage, more sensitive and accurate than total liver area.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142668125","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}

{"title":"Association of Stress Defense System With Fine Particulate Matter Exposure: Mechanism Analysis and Application Prospects.","authors":"Tao Meng, Jing He, Qianru Huo, Yajie Wang, Qingchun Ren, Yihui Kang","doi":"10.1002/jat.4724","DOIUrl":"https://doi.org/10.1002/jat.4724","url":null,"abstract":"<p><p>The association between the stress defense system and exposure to fine particulate matter (PM_2.5) is a hot topic in the field of environmental health. PM_2.5 pollution is an increasingly serious issue, and its impact on health cannot be ignored. The stress defense system is an important biological mechanism for maintaining cell and internal environment homeostasis, playing a crucial role in PM_2.5-induced damage and diseases. The association between PM_2.5 exposure and activation of the stress defense system has been reported. Moderate PM_2.5 exposure rapidly mobilizes the stress defense system, while excessive PM_2.5 exposure may exceed its compensatory and coping abilities, resulting in system imbalance and dysfunction that triggers pathological changes in cells and tissues, thereby increasing the risk of chronic diseases, such as respiratory diseases, cardiovascular diseases, and cancer. This detailed review focuses on the composition, function, and regulatory mechanisms of the antioxidant defense system, autophagy system, ubiquitin-proteasome system, and inflammatory response system, which are all components of the stress defiance system. In particular, the influence of PM_2.5 exposure on each of these defense systems and their roles in responding to PM_2.5-induced damage was investigated to provide an in-depth understanding of the pathogenesis of PM_2.5 exposure, accurately assess potential hazards, and formulate prevention and intervention strategies for health damage caused by PM_2.5 exposure.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621020","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}

{"title":"The Impact of NO₂ on Epithelial Barrier Integrity of a Primary Cell-Based Air-Liquid Interface Model of the Nasal Respiratory Epithelium.","authors":"Helena Moratin, Josephine Lang, Magdalena-Sophie Picker, Angela Rossi, Christian Wilhelm, Armin von Fournier, Manuel Stöth, Miguel Goncalves, Norbert Kleinsasser, Stephan Hackenberg, Agmal Scherzad, Till Jasper Meyer","doi":"10.1002/jat.4717","DOIUrl":"https://doi.org/10.1002/jat.4717","url":null,"abstract":"<p><p>Nitrogen dioxide (NO₂) is a pervasive gaseous air pollutant with well-documented hazardous effects on health, necessitating precise toxicological characterization. While prior research has primarily focused on lower airway structures, the upper airways, serving as the first line of defense against airborne substances, remain understudied. This study aimed to investigate the functional effects of NO₂ exposure alone or in combination with hypoxia as a secondary stimulus on nasal epithelium and elucidate its molecular mechanisms because hypoxia is considered a pathophysiological factor in the onset and persistence of chronic rhinosinusitis, a disease of the upper airways. Air-liquid interface cell cultures derived from primary nasal mucosa cells were utilized as an in vitro model, offering a high in vitro-in vivo correlation. Our findings demonstrate that NO₂ exposure induces malfunction of the epithelial barrier, as evidenced by decreased transepithelial electrical resistance and increased fluorescein isothiocyanate (FITC)-dextran permeability. mRNA expression analysis revealed a significant increase in IL-6 and IL-8 expressions following NO₂. Reduced mRNA expression of the tight junction component occludin was identified as a structural correlate of the damaged epithelial barrier. Notably, hypoxic conditions alone did not alter epithelial barrier integrity. These findings provide information on the harmful effects of NO₂ exposure on the human nasal epithelium, including compromised barrier integrity and induction of inflammatory responses. Overall, this study contributes to our understanding of pathophysiological mechanisms underlying also upper airway respiratory diseases associated with air pollution exposure and emphasizes the importance of mitigating NO₂ emissions to safeguard respiratory health.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621148","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}

{"title":"The Role of PI3K/AKT/HIF-1α Pathway in the Effect of Nano-TiO₂ on Lactate Production in TM4 Cells.","authors":"Hongmei Chang, Siqi Zhao, Yuzhu Lei, Yunhua Hu, Yizhong Yan, Guanling Song","doi":"10.1002/jat.4725","DOIUrl":"https://doi.org/10.1002/jat.4725","url":null,"abstract":"<p><p>Titanium dioxide nanoparticles (nano-TiO₂) can cause a reduction in sperm counts, and lactate production in Sertoli cells plays a key role in spermatogenesis. The aim of this study was to evaluate the effect of nano-TiO₂ on lactate production in mouse Sertoli cell line (TM4 cells) and to investigate whether the effect is mediated through the PI3K/AKT/HIF-1α pathway. After TM4 cells were treated with different concentrations of nano-TiO₂ for 48 h, cell viability, contents of glucose and lactate, and the expression levels of GLUT3 and key enzymes (HK1, HK2, PFKM, ENO1, LDH) during lactate production were detected. PI3K/AKT/HIF-1α pathway proteins were measured. In addition, PI3K agonist (IGF-1) was added to explore whether nano-TiO₂ regulates HIF-1α through PI3K/AKT pathway, thereby affecting the production of lactate in TM4 cells. The results showed that nano-TiO₂ significantly inhibited TM4 cell viability, increased glucose content, decreased lactate content, and downregulated the expression levels of GLUT3 and key enzymes during lactate production. Meanwhile, nano-TiO₂ decreased the expression of PI3K/AKT pathway phosphorylated proteins and HIF-1α, and IGF attenuated this effect of nano-TiO₂. Collectively, nano-TiO₂ downregulated the expression level of proteins and enzymes related to lactate production in TM4 cells by inhibiting PI3K/AKT/HIF-1α pathway, resulting in the decrease of lactate production in TM4 cells.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621153","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}

{"title":"Health Implications of Depleted Uranium: An Update.","authors":"Hong Wang, Liang Li, Xiaolin Fan, Yuhao Zhang, Qing Lu, Ning Ma, Boya Yu, Xiao Li, Junhong Gao","doi":"10.1002/jat.4720","DOIUrl":"https://doi.org/10.1002/jat.4720","url":null,"abstract":"<p><p>Depleted uranium (DU), as a heavy metal material extensively utilized in the industrial sector, poses potential health risks to humans through various exposure pathways, including inhalation, ingestion, and dermal contact. To comprehensively understand the toxicological hazards of DU, this study conducted a literature search in the Web of Science Core Collection database using \"DU\" and \"toxicity\" as keywords, covering the period from January 2000 to December 2023. A total of 65 papers related to human, animal, or cellular studies on DU were included. This review delves into the latest research advancements on the origin and toxicokinetics of DU, as well as its pulmonary toxicity, neurotoxicity, nephrotoxicity, immunotoxicity, hepatotoxicity, reproductive toxicity, cancer, bone toxicity, and hematological toxicity. The aim of this review is to gain a deeper understanding of the health hazards posed by DU, which is of significant importance for formulating corresponding protection strategies and measures.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621120","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}

{"title":"The Relationship Between Mercury Exposure and Membranous Nephropathy: Case Reports and Meta-Analysis.","authors":"Jian-Yuan Zhong, Ya-Qi Mo, Meng-Jun Teng, Jian-Chao Peng, Kang Nong, Michael Aschner, Dan-Ling Yang, Yue-Ming Jiang","doi":"10.1002/jat.4721","DOIUrl":"https://doi.org/10.1002/jat.4721","url":null,"abstract":"<p><p>To investigate the clinical characteristics of patients with membranous nephropathy (MN) and the therapeutic efficacy of Sodium Dimercaptosulphonate (DMPS), as well as the relationship between mercury (Hg) exposure and MN, we investigated the clinical manifestations and treatment outcomes of six patients with MN and searched the China National Knowledge Internet (CNKI), PubMed, Web Of Science, and Embase databases for relevant studies on Hg exposure and MN published from the inception of the databases to April 2024. Data analysis was performed using SPSS 26.0 and Stata 16.0. We found that (1) the clinical symptoms of MN patients were mainly characterized by proteinuria, edema, hypoproteinemia, and hyperlipidemia. Comparative analysis before and after DMPS treatment showed a decrease in 24-h urinary Hg, 24-h urinary protein, and total cholesterol levels, as well as an increase in serum albumin levels (p < 0.05). (2) Two MN patients received DMPS for sole Hg detoxification treatment, whereas four patients received Hg detoxification combined with hormone therapy, and all patients showed significant improvement in symptoms after treatment. (3) Among the 564 articles, four met the inclusion criteria. The results showed that Hg exposure increased the incidence of MN by 5.74 times (95% confidence interval [CI] = 2.57, 12.83). The clinical symptoms of MN patients are mostly manifested as proteinuria, edema, hypoproteinemia, and hyperlipidemia. DMPS Hg detoxification treatment is effective for Hg-induced MN. Hg exposure can increase the prevalence of MN, therefore making it necessary to take prudent measures to reduce the risk of Hg exposure.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621151","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}

{"title":"Caenorhabditis elegans as a Model for Evaluating the Toxicology of Inorganic Nanoparticles.","authors":"Aline Castro Silva, Gabriel Pedroso Viçozzi, Marcelo Farina, Daiana Silva Ávila","doi":"10.1002/jat.4704","DOIUrl":"10.1002/jat.4704","url":null,"abstract":"<p><p>Inorganic nanoparticles are nanomaterials with a central core composed of inorganic specimens, especially metals, which give them interesting applications but can impact the environment and human health. Their short- and long-term effects are not completely known and to investigate that, alternative models have been successfully used. Among these, the nematode Caenorhabditis elegans has been increasingly applied in nanotoxicology in recent years because of its many features and advantages for toxicological screening. This non-parasitic nematode may inhabit any environment where organic matter is available; therefore, it is interesting for ecotoxicological assessments. Moreover, this worm has a high genetic homology to humans, making the findings translatable. A notable number of published studies unraveled the level of toxicity of different nanoparticles, including the mechanisms by which their toxicity occurs. This narrative review collects and describes the most relevant toxicological data for inorganic nanoparticles obtained using C. elegans and also supports its application in safety assessments for regulatory purposes.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590817","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}

{"title":"Palmitic Acid Induced a Dedifferentiation Profile at the Transcriptome Level: A Collagen Synthesis but no Triglyceride Accumulation in Hepatocyte-Like Cells Derived From Human-Induced Pluripotent Stem Cells Cultivated Inside Organ on a Chip.","authors":"Hanyuan Wang, Mathieu Danoy, Ya Gong, Tia Utami, Hiroshi Arakawa, Yukio Kato, Masaki Nishikawa, Yasuyuki Sakai, Eric Leclerc","doi":"10.1002/jat.4714","DOIUrl":"https://doi.org/10.1002/jat.4714","url":null,"abstract":"<p><p>Nonalcoholic fatty liver disease (NAFLD) is one of the main causes of critical liver diseases leading to steatosis, steatohepatitis, fibrosis, and ultimately to liver cirrhosis and hepatic carcinoma. In this study, the effect of palmitic acid (PA), one of the most abundant dietary fatty acids, was investigated using an organ-on-a-chip (OoC) technology on hepatocyte-like cells derived from human-induced pluripotent stem cells (hiPSCs). After 1 week of hepatic maturation, followed by 1 week of exposure, the transcriptomic analysis showed lower liver transcription factor activity. It also revealed that 318 genes were differentially expressed between the control and 0.5-mM PA conditions. The 0.5-mM PA conditions were characterized by the downregulation of hepatic markers (liver transcription factors, phase I and phase II metabolism genes) of lipidic genes (metabolism and transport). In parallel, the 0.5-mM PA treatment upregulated several extracellular matrix genes (such as collagen genes). The physiopathological staining demonstrated no lipid accumulation in our model and confirmed the secretion of collagen in the 0.5-mM PA conditions. However, the production of albumin, the metabolic biotransformation by the cytochrome P450 enzymes, and the biliary acid concentrations were not altered by the PA treatments. Overall, our data illustrated the response to PA characterized by an early stage of dedifferentiation observed at the transcriptomic levels associated with a modification of the collagenic profile but without lipid accumulation. We believe that our model provides new insight of the onset of palmitic lipotoxicity in the early stage of NAFLD.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590818","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}

{"title":"Oxidative Stress and Inflammation in Myocardial Ischemia-Reperfusion Injury: Protective Effects of Plant-Derived Natural Active Compounds.","authors":"Jia Chen, Boyu Wang, Tianwei Meng, Chengjia Li, Changxing Liu, Qingnan Liu, Jiameng Wang, Zhiping Liu, Yabin Zhou","doi":"10.1002/jat.4719","DOIUrl":"https://doi.org/10.1002/jat.4719","url":null,"abstract":"<p><p>Acute myocardial infarction (AMI) remains a leading cause of death among patients with cardiovascular diseases. Percutaneous coronary intervention (PCI) has been the preferred clinical treatment for AMI due to its safety and efficiency. However, research indicates that the rapid restoration of myocardial oxygen supply following PCI can lead to secondary myocardial injury, termed myocardial ischemia-reperfusion injury (MIRI), posing a grave threat to patient survival. Despite ongoing efforts, the mechanisms underlying MIRI are not yet fully elucidated. Among them, oxidative stress and inflammation stand out as critical pathophysiological mechanisms, playing significant roles in MIRI. Natural compounds have shown strong clinical therapeutic potential due to their high efficacy, availability, and low side effects. Many current studies indicate that natural compounds can mitigate MIRI by reducing oxidative stress and inflammatory responses. Therefore, this paper reviews the mechanisms of oxidative stress and inflammation during MIRI and the role of natural compounds in intervening in these processes, aiming to provide a basis and reference for future research and development of drugs for treating MIRI.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557928","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}

{"title":"Neurotoxicity and Cardiovascular Toxicity of Zinc Oxide Nanoparticles to Oryzias melastigma.","authors":"Sheikh Shohag, Yoshifumi Horie","doi":"10.1002/jat.4718","DOIUrl":"https://doi.org/10.1002/jat.4718","url":null,"abstract":"<p><p>Zinc oxide nanoparticles (ZnO NPs) are widely used in manufacturing cosmetic and pharmaceutical products. Although previous studies have reported their toxic effects on fish, the underlying mechanisms behind their toxic effects are yet to be identified. This study evaluated the impact of ZnO NPs on marine medaka's survival, heart rates (Oryzias melastigma), and the expression of genes linked to neurotoxicity and cardiovascular toxicity. Marine medaka samples were exposed to ZnO NPs at varying concentrations: 0.01, 0.1, 1, and 10 mg/L. Survival rates and heart rates were monitored on the 12th day postfertilization. Gene expression related to neurotoxicity (α-tubulin, elavl3, gap43, gfap) and cardiovascular toxicity (cdh2, atp2a1, cacna1da, crhr1, ahrra, arnt2) was assessed by performing real-time polymerase chain reaction. The survival rate of marine medaka samples was not significantly impacted by exposure to up to 1 mg/L of ZnO NPs; however, exposure to 10 mg/L of ZnO NPs resulted in a 60% reduction in survival rate. The heart rate of the samples did not significantly change across all concentrations. High ZnO NP concentrations (10 mg/L) significantly suppressed the expression of neurotoxic and cardiotoxic genes, including elavl3 and gfap. ZnO NPs exhibited dose-dependent toxic effects on the marine medaka samples by affecting the expression of genes related to neurological and cardiovascular functions. These findings underscore the potential risks of ZnO NPs to aquatic organisms. The distinct toxic actions of ZnO NPs and dissolved ions complicate the interpretation of results, as this study did not measure ion release, a critical factor in understanding NP toxicity. Moreover, ZnO NPs may cause oxidative stress and disrupt cellular pathways. Furthermore, without distinguishing between NP and ion effects, it is challenging to determine the exact cause of toxicity. These findings highlight the need for future studies to measure dissolved ions and particles separately to clarify their contributions to toxicity, where the mechanisms of action are still debated.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557927","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}