Journal of Applied Toxicology最新文献

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The Relationship Between Mercury Exposure and Membranous Nephropathy: Case Reports and Meta-Analysis 汞暴露与膜性肾病的关系:病例报告与 Meta 分析
IF 2.7 4区 医学
Journal of Applied Toxicology Pub Date : 2024-11-08 DOI: 10.1002/jat.4721
Jian-Yuan Zhong, Ya-Qi Mo, Meng-Jun Teng, Jian-Chao Peng, Kang Nong, Michael Aschner, Dan-Ling Yang, Yue-Ming Jiang
{"title":"The Relationship Between Mercury Exposure and Membranous Nephropathy: Case Reports and Meta-Analysis","authors":"Jian-Yuan Zhong,&nbsp;Ya-Qi Mo,&nbsp;Meng-Jun Teng,&nbsp;Jian-Chao Peng,&nbsp;Kang Nong,&nbsp;Michael Aschner,&nbsp;Dan-Ling Yang,&nbsp;Yue-Ming Jiang","doi":"10.1002/jat.4721","DOIUrl":"10.1002/jat.4721","url":null,"abstract":"<div>\u0000 \u0000 <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 (<i>p</i> &lt; 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>\u0000 </div>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":"45 3","pages":"472-481"},"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}
引用次数: 0
Caenorhabditis elegans as a Model for Evaluating the Toxicology of Inorganic Nanoparticles. 将秀丽隐杆线虫作为评估无机纳米颗粒毒理学的模型
IF 2.7 4区 医学
Journal of Applied Toxicology Pub Date : 2024-11-06 DOI: 10.1002/jat.4704
Aline Castro Silva, Gabriel Pedroso Viçozzi, Marcelo Farina, Daiana Silva Ávila
{"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}
引用次数: 0
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 棕榈酸诱导转录组水平的去分化特征:在芯片器官内培养的人类诱导多能干细胞衍生出的肝细胞样细胞中胶原合成,但无甘油三酯积累。
IF 2.7 4区 医学
Journal of Applied Toxicology Pub Date : 2024-11-06 DOI: 10.1002/jat.4714
Hanyuan Wang, Mathieu Danoy, Ya Gong, Tia Utami, Hiroshi Arakawa, Yukio Kato, Masaki Nishikawa, Yasuyuki Sakai, Eric Leclerc
{"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,&nbsp;Mathieu Danoy,&nbsp;Ya Gong,&nbsp;Tia Utami,&nbsp;Hiroshi Arakawa,&nbsp;Yukio Kato,&nbsp;Masaki Nishikawa,&nbsp;Yasuyuki Sakai,&nbsp;Eric Leclerc","doi":"10.1002/jat.4714","DOIUrl":"10.1002/jat.4714","url":null,"abstract":"<div>\u0000 \u0000 <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>\u0000 </div>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":"45 3","pages":"460-471"},"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}
引用次数: 0
Oxidative Stress and Inflammation in Myocardial Ischemia-Reperfusion Injury: Protective Effects of Plant-Derived Natural Active Compounds. 心肌缺血再灌注损伤中的氧化应激和炎症:植物提取的天然活性化合物的保护作用
IF 2.7 4区 医学
Journal of Applied Toxicology Pub Date : 2024-10-31 DOI: 10.1002/jat.4719
Jia Chen, Boyu Wang, Tianwei Meng, Chengjia Li, Changxing Liu, Qingnan Liu, Jiameng Wang, Zhiping Liu, Yabin Zhou
{"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}
引用次数: 0
Neurotoxicity and Cardiovascular Toxicity of Zinc Oxide Nanoparticles to Oryzias melastigma 氧化锌纳米颗粒对黑鲔鱼的神经毒性和心血管毒性
IF 2.7 4区 医学
Journal of Applied Toxicology Pub Date : 2024-10-31 DOI: 10.1002/jat.4718
Sheikh Shohag, Yoshifumi Horie
{"title":"Neurotoxicity and Cardiovascular Toxicity of Zinc Oxide Nanoparticles to Oryzias melastigma","authors":"Sheikh Shohag,&nbsp;Yoshifumi Horie","doi":"10.1002/jat.4718","DOIUrl":"10.1002/jat.4718","url":null,"abstract":"<div>\u0000 \u0000 <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 (<i>Oryzias melastigma</i>), 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 (<i>α-tubulin</i>, <i>elavl3</i>, <i>gap43</i>, <i>gfap</i>) and cardiovascular toxicity (<i>cdh2</i>, <i>atp2a1</i>, <i>cacna1da</i>, <i>crhr1</i>, <i>ahrra</i>, <i>arnt2</i>) 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 <i>elavl3</i> and <i>gfap</i>. 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>\u0000 </div>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":"45 3","pages":"452-459"},"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}
引用次数: 0
Preclinical Evaluation of Protective Effects of Terpenoids Against Nanomaterial-Induced Toxicity: A Meta-Analysis. 萜类化合物对纳米材料引发的毒性的保护作用的临床前评估:元分析。
IF 2.7 4区 医学
Journal of Applied Toxicology Pub Date : 2024-10-30 DOI: 10.1002/jat.4716
Yuexiao Sun, Yang Zhou, Dongli Xie, Xuejiao Wang, Ya Wang, Yunxia Liang, Xiaogang Luo
{"title":"Preclinical Evaluation of Protective Effects of Terpenoids Against Nanomaterial-Induced Toxicity: A Meta-Analysis.","authors":"Yuexiao Sun, Yang Zhou, Dongli Xie, Xuejiao Wang, Ya Wang, Yunxia Liang, Xiaogang Luo","doi":"10.1002/jat.4716","DOIUrl":"https://doi.org/10.1002/jat.4716","url":null,"abstract":"<p><p>Terpenoids, the largest class of natural products, have been demonstrated to confer antioxidant, anti-inflammatory, anti-apoptotic, and antitumor activities. However, whether terpenoids benefit populations exposed to nanomaterials through these mechanisms remains unclear. This meta-analysis was to evaluate the effects of terpenoids in preclinical models with nanomaterial exposure. Electronic database searching identified 39 studies. The meta-analysis by Stata 15.0 showed that terpenoid supplementation significantly improved cell viability and altered oxidative stress (decreased ROS, NO, MDA, and TOC and increased SOD, CAT, GPx, GSH, GSH-Px, and TAC)-, inflammation (decreased IL-6, IL-1β, TNF-α, NF-κB, monocytes, and increased IL-10)-, apoptosis (reduced Bax, caspase-3, caspase-9, P53, and elevated Bcl-2)-, genotoxic (reduced tail length, % tail DNA, tail moment, DNA fragmentation, chromosomal aberration, and MNPCEs)-, liver function (reduced ALT, AST, and ALP)-, renal function (reduced creatinine, urea, and uric acid)-, reproductive function (increased sperm count, testosterone, Johnsen's score, and number of progeny)-, lipid profile (lower cholesterol, TG, LDL, and higher HDL)-, and carcinogenesis (downregulated AFP and CEA)-related biomarkers induced by nanomaterials. Subgroup analysis indicated that monoterpenoids and tetraterpenoids were particularly effective. Collectively, terpenoids may be a promising candidate for prevention of toxicities caused by nanomaterials.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545670","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
Borderline Range Determined Using Data From Validation Study of Alternative Methods for Skin Sensitization: ADRA, IL-8 Luc Assay, and EpiSensA 使用皮肤过敏替代方法验证研究的数据确定边界范围:ADRA、IL-8 Luc Assay 和 EpiSensA。
IF 2.7 4区 医学
Journal of Applied Toxicology Pub Date : 2024-10-30 DOI: 10.1002/jat.4712
Toshihiko Kasahara, Yusuke Yamamoto, Natsumi Nakashima, Mika Imamura, Hideyuki Mizumachi, Sho Suzuki, Setsuya Aiba, Yutaka Kimura, Takao Ashikaga, Hajime Kojima, Atsushi Ono, Kazuhiko Matsumoto
{"title":"Borderline Range Determined Using Data From Validation Study of Alternative Methods for Skin Sensitization: ADRA, IL-8 Luc Assay, and EpiSensA","authors":"Toshihiko Kasahara,&nbsp;Yusuke Yamamoto,&nbsp;Natsumi Nakashima,&nbsp;Mika Imamura,&nbsp;Hideyuki Mizumachi,&nbsp;Sho Suzuki,&nbsp;Setsuya Aiba,&nbsp;Yutaka Kimura,&nbsp;Takao Ashikaga,&nbsp;Hajime Kojima,&nbsp;Atsushi Ono,&nbsp;Kazuhiko Matsumoto","doi":"10.1002/jat.4712","DOIUrl":"10.1002/jat.4712","url":null,"abstract":"<div>\u0000 \u0000 <p>Most predictive models that use alternatives to animal experiments divide judgements into two classes with a cutoff value for each model. However, if the results of alternative methods are close to the cutoff values, the true result may be ambiguous because of variability in the data. Therefore, the OECD GL497 uses a judgement method that establishes a borderline range (BR) around a cutoff value using a statistical method. However, because there is no detailed description of how the BR is calculated, we clarified two specific points. The scale-constant correction method was used to calculate the median absolute deviation (MAD) around the median. In addition, the bottom-raised transformation method was used when the data were “0” because calculation of the BR requires that all data are logarithmic. Indeed, the BRs for the amino acid derivative reactivity assay (ADRA), interleukin-8 reporter gene assay (IL-8 Luc), and epidermal sensitization assay (EpiSensA) were calculated using data from each validation study. The results showed that the BR for ADRA and IL-8 Luc ranged from 4.1 to 5.9 and 1.25 to 1.57, respectively. Furthermore, the BRs of four genes (<i>ATF3</i>, <i>GCLM</i>, <i>DNAJB4</i>, and <i>IL-8</i>) evaluated using EpiSensA ranged from 10.71 to 21.02, 1.64 to 2.45, 1.61 to 2.52, and 3.11 to 5.16, respectively. The difference (deviation) between the lower and upper BR limits and cutoff value for each alternative method were comparable to those of the alternative methods listed in the guidelines (DPRA, KerarinoSens, and h-CLAT) and thus were considered as adequate.</p>\u0000 </div>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":"45 3","pages":"432-439"},"PeriodicalIF":2.7,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545668","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
Effects of MDA-19 on Zebrafish Larval Behavior: Perspectives From Neurodevelopment, Oxidative Stress, and Metabolomics MDA-19 对斑马鱼幼体行为的影响:神经发育、氧化应激和代谢组学的视角
IF 2.7 4区 医学
Journal of Applied Toxicology Pub Date : 2024-10-30 DOI: 10.1002/jat.4715
Boyang Xu, Jun Yan, Yangtao Zhou, Feng Zhang, Binjie Wang, Jiye Wang, Yuanzhao Wu, Yu Xu
{"title":"Effects of MDA-19 on Zebrafish Larval Behavior: Perspectives From Neurodevelopment, Oxidative Stress, and Metabolomics","authors":"Boyang Xu,&nbsp;Jun Yan,&nbsp;Yangtao Zhou,&nbsp;Feng Zhang,&nbsp;Binjie Wang,&nbsp;Jiye Wang,&nbsp;Yuanzhao Wu,&nbsp;Yu Xu","doi":"10.1002/jat.4715","DOIUrl":"10.1002/jat.4715","url":null,"abstract":"<div>\u0000 \u0000 <p>As global regulations on synthetic cannabinoids tighten, illicit vendors increasingly turn to new structures of synthetic cannabinoids to evade legal scrutiny. MDA-19, a novel synthetic cannabinoid, exhibited significant agonistic effects on type 2 cannabinoid receptors in vivo and showed emerging trends of abuse in illicit markets. However, research on the toxicological effects of MDA-19 remains scarce. In this study, we examined the effects of MDA-19 on neurodevelopment, behavior, oxidative stress, and metabolomics by exposing zebrafish embryos to MDA-19 solutions with concentrations of 1, 10, and 20 mg/L over 5 days. Results revealed that exposure to 10 and 20 mg/L of MDA-19 accelerated hatching in zebrafish embryos but led to reduced body length without affecting mortality or malformation. Furthermore, exposure to all concentrations of MDA-19 resulted in diminished swimming ability and reduced activity time in zebrafish. Transgenic zebrafish (<i>hb9</i>-GFP) exposed to MDA-19 exhibited impaired development of spinal motor neurons. Notably, exposure to 20 mg/L MDA-19 increased the levels of reactive oxygen species (ROS) in zebrafish and elevated the activity of antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT), while the levels of the lipid oxidation product malondialdehyde (MDA) remained unaffected. Nontargeted metabolomics analyses showed that MDA-19 interfered with multiple metabolic pathways affecting energy metabolism, such as alanine, aspartate, and glutamate metabolism; the citric acid cycle (TCA cycle), pantothenate, and coenzyme A biosynthesis; and purine metabolism. In conclusion, the present study provided the essential evidence for the neurotoxic effects of MDA-19, which was associated with impaired neurodevelopment, dysregulation of oxidative stress homeostasis, and altered energy metabolism.</p>\u0000 </div>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":"45 3","pages":"440-451"},"PeriodicalIF":2.7,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545669","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
Effects of WN1703 on Cardiovascular Function in Chronic Hyperuricemia Rats and Myocardial Injury Mechanism Exploration in H9C2 Cells WN1703 对慢性高尿酸血症大鼠心血管功能的影响及 H9C2 细胞心肌损伤机制探索
IF 2.7 4区 医学
Journal of Applied Toxicology Pub Date : 2024-10-22 DOI: 10.1002/jat.4710
Xiaodan Lu, Fuyao Liu, Hongming Chen, Haojie Cai, Lei Zhang, Jing Li
{"title":"Effects of WN1703 on Cardiovascular Function in Chronic Hyperuricemia Rats and Myocardial Injury Mechanism Exploration in H9C2 Cells","authors":"Xiaodan Lu,&nbsp;Fuyao Liu,&nbsp;Hongming Chen,&nbsp;Haojie Cai,&nbsp;Lei Zhang,&nbsp;Jing Li","doi":"10.1002/jat.4710","DOIUrl":"10.1002/jat.4710","url":null,"abstract":"<div>\u0000 \u0000 <p>Hyperuricemia, a prevalent condition, is typically preceded by disturbances in purine metabolism and is frequently associated with hyperlipidemia and other dysfunctions of metabolism. WN1703 demonstrated an inhibitory activity against xanthine oxidoreductase (XOR) that was comparable to febuxostat in our prior investigation. In this study, we assessed the cardiovascular safety of WN1703 in a chronic hyperuricemia rat model induced by potassium oxonate in combination with hypoxanthine. We investigated the changes in cardiovascular biomarkers in chronic hyperuricemia rats treated with febuxostat and WN1703, including creatine kinase (CK), CK-MB, B type natriuretic peptide (BNP), Corin protein (CRN), Neprilysin (NEP), myeloperoxidase (MPO), 8-hydroxy-2-deoxyguanosine (8-OHdG), tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), and interleukin-8 (IL-8). Additionally, we validated the potential mechanism of cardiac injury induced by WN1703 in H9C2 cells, guided by cardiotoxicity predictions from the cardioToxCSM database and network pharmacology. We observed that excessively rapid urate-lowering, oxidative stress, and inflammation could disrupt myocardial functional homeostasis and increase the risk of cardiovascular injury in hyperuricemia rats, and WN1703 treatment effectively reduced the levels oxidative stress marker 8-OHdG and inflammatory factor TNF-α. Despite the absence of organic damage to the heart with prolonged treatment of febuxostat and WN1703, potential hazard of cardiovascular injury could be associated with the modulation of the TGFβ and RHO/ROCK signaling pathways by febuxostat and WN1703. This could offer new insights into the mechanisms underlying the adverse effects caused by XOR inhibitors.</p>\u0000 </div>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":"45 3","pages":"418-431"},"PeriodicalIF":2.7,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466401","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
The Impact of Genetic Polymorphisms for Detecting Genotoxicity in Workers Occupationally Exposed to Metals: A Systematic Review. 基因多态性对检测职业接触金属工人遗传毒性的影响:系统回顾
IF 2.7 4区 医学
Journal of Applied Toxicology Pub Date : 2024-10-21 DOI: 10.1002/jat.4711
Thiago Guedes Pinto, Thayza Aires Dias, Ana Claudia Muniz Renno, Jean Nunes Dos Santos, Patrícia Ramos Cury, Daniel Araki Ribeiro
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