Journal of Applied Toxicology最新文献

{"title":"Safety Assessment of Butyric Acid-Rich Triglyceride Oil: A Novel Palatable Formulation of Butyrate for the Pediatric Population","authors":"John A. Watson, Sophie Nutten, Angelique Groot, Roy Hoffmans, Lars Damen, Eleonore Olivier, John Barnett Jr, Amaury Patin","doi":"10.1002/jat.4729","DOIUrl":"10.1002/jat.4729","url":null,"abstract":"<div>\u0000 \u0000 <p>A novel, palatable butyric acid-rich triglyceride oil has been developed and is available as a food supplement for adults in the United States and Canada. A program of safety studies was conducted with butyric acid-rich triglyceride oil for the pediatric population.</p>\u0000 <p>The oil was tested in a microbial reverse mutation assay Ames Test OECD471 (Organisation for Economic Co-operation and Development) in which all bacterial strains showed negative responses over the complete dose range in two independently repeated experiments. All values were within the laboratory historical control data ranges. Further, data from the human lymphocyte micronucleus assay (OECD487) in the presence or absence of a metabolic activator (S9-mix), the oil did not induce a biologically relevant increase in the number of binucleated cells with micronuclei; therefore, the oil is considered not to be clastogenic or aneugenic. In a 90-day rat repeat dose toxicity study (OECD408), there were no unscheduled deaths, no treatment-related clinical signs, or effects on body weight and body weight gain, food consumption, ophthalmology, FOB parameters (including motor activity), clinical chemistry including thyroid hormones, and sperm parameters. There were no related organ weight changes, macroscopic or microscopic findings. In an extended one-generation reproductive toxicology study (EOGRTS) OECD443, there were no biologically important changes in body weight or body weight gain observed in the P generation male rats during the dosing period. At the end of the dosing period, the mean body weights in the male rats were 98% and 98% of the control group value in the 3720 and 4650 mg/kg/day dose groups, respectively. No biologically important changes in maternal body weights or body weight gains were observed during the premating, gestation, or lactation periods at dose levels up to and including 4650 mg/kg/day. Clinical signs observed in the P generation males and females were within the historical data ranges and not test substance related. There were no test substance-related changes in any other tested outcomes analyzed in the P generation males and females at doses up to and including 4650 mg/kg/day. In the F1 Generation, preweaning clinical signs observed in the males and females were within the historical data ranges and not test article related. There were no statistically significant or biologically relevant abnormalities in any of the parameters analyzed throughout the preweaning period at maternal dose levels up to and including 4650 mg/kg/day. In the postweaning period, there were also no clinical signs observed in males and females; all were within the historical data ranges and not test article related. There were no statistically significant or biologically relevant abnormalities in any of the parameters analyzed throughout the postweaning period at maternal dose levels up to and including 4650 mg/kg/day including body weights. Tak","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":"45 4","pages":"587-605"},"PeriodicalIF":2.7,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142750730","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":"Exposure of Porcine Oocytes to Methylparaben During In Vitro Maturation Alters the Expression of Genes Involved in Cumulus Cell Expansion and Steroidogenesis, Decreasing Hyaluronic Acid and Progesterone Synthesis","authors":"Adyeni Barajas-Salinas,&nbsp;Iván Bahena,&nbsp;Juan José Rodríguez-Mercado,&nbsp;Lizbeth Juárez-Rojas,&nbsp;Miguel Betancourt,&nbsp;Elivier Núñez-Macías,&nbsp;Yenny Ramírez-Jara,&nbsp;Alma López,&nbsp;Eduardo Casas,&nbsp;Edmundo Bonilla,&nbsp;Zayil Salazar,&nbsp;Fahiel Casillas","doi":"10.1002/jat.4727","DOIUrl":"10.1002/jat.4727","url":null,"abstract":"<div>\u0000 \u0000 <p>Parabens are widely used because of their antimicrobial properties in drugs, cosmetics, and food; however, it has been reported that methylparaben may adversely influence female reproduction. Methylparaben decreases oocyte in vitro maturation at a maturation inhibition concentration 50 of 780.31 μM but also decreases oocyte viability at a lethal concentration 50 of 2028.38 μM. Additionally, parabens are endocrine disruptors, affecting steroidogenesis as well as cumulus cell expansion. Therefore, the aim of this study was to elucidate some of the mechanisms by which methylparaben alters cumulus cell expansion and decreases oocyte maturation through the evaluation of gene expression related to cumulus cell expansion, hyaluronic acid, and progesterone synthesis. For this, oocytes were exposed to different methylparaben concentrations of 0 (control), 650, 780, and 1000 μM for 20 and 44 h of in vitro maturation. The cumulus cell expansion rates, maturation rates, gene expression rates, and hyaluronic acid and progesterone concentrations were revaluated after 20 and 44 h of culture. At sublethal concentrations, methylparaben decreased in vitro maturation as well as cumulus cell expansion at 44 h. Additionally, methylparaben decreased the expression of <i>Has2</i> and <i>Cd44</i> at 20 and 44 h of maturation. The expression levels of <i>Stard1</i>, <i>Cyp11a1</i>, and <i>Hsd3b1</i> were also altered by methylparaben exposure at 20 and 44 h of maturation, suggesting its role as an endocrine disruptor. Hyaluronic acid and progesterone concentrations in the culture medium decreased at 20 and 44 h. These findings could partially explain some of the mechanisms by which methylparaben alters female fertility.</p>\u0000 </div>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":"45 4","pages":"563-575"},"PeriodicalIF":2.7,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142716306","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":"Erythrosine-Induced Neurotoxicity: Evaluating Enzymatic Dysfunction, Oxidative Damage, DNA Damage, and Histopathological Alterations in Wistar Rats","authors":"Mandeep Singh,&nbsp;Pooja Chadha","doi":"10.1002/jat.4731","DOIUrl":"10.1002/jat.4731","url":null,"abstract":"<div>\u0000 \u0000 <p>Erythrosine, a synthetic red dye widely used in food products, has been linked to potential health risks, raising concerns about its safety. This study aimed to evaluate the subacute toxicity of the synthetic food dye erythrosine in the brains of Wistar rats. Twenty-four 6- to 7-week-old female rats were randomly divided into four groups of six (<i>n</i> = 6); the control group and the other three groups, which were established on the basis of erythrosine's acceptable daily intake (ADI, 0.1 mg per kg body weight); 1/4 ADI, 1/2 ADI, and ADI; for 28 days. Significant alterations in the enzymatic activity of catalase (CAT), superoxide dismutase (SOD), glutathione-S-transferase (GST), and acetylcholinesterase (AchE) were observed at all erythrosine dosages, with a substantial decline at ADI dosages (<i>p</i> ≤ 0.05). Increased oxidative stress markers, viz., malondialdehyde content and lactate dehydrogenase activity, were observed in ADI-administered rats. The H₂O₂ content decreased at 1/4 ADI and 1/2 ADI dosages and thereafter increased with increasing dosage. The comet assay demonstrated that the ADI dosage for 28 days resulted in the most significant damage, as evidenced by the increased tail length, tail DNA percentage, and tail moment. Light microscopy revealed various anomalies in brain histology, such as atrophies, vacuolization, shrunken cells, pyknotic nuclei, and reduced cell density. The results of the present study demonstrated that erythrosine disrupts the normal histopathology of the brain, suppresses antioxidative and acetylcholinesterase enzymatic activity, and increases lipid peroxidation and DNA damage, thereby resulting in erythrosine toxicity even at doses lower than the ADI.</p>\u0000 </div>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":"45 4","pages":"576-586"},"PeriodicalIF":2.7,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142728308","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":"Ergothioneine Ameliorates Liver Fibrosis by Inhibiting Glycerophospholipids Metabolism and TGF-β/Smads Signaling Pathway: Based on Metabonomics and Network Pharmacology","authors":"Yaping Mao,&nbsp;Zhenghui Xie,&nbsp;Xiangxia Zhang,&nbsp;Yu Fu,&nbsp;Xiaotong Yu,&nbsp;Lili Deng,&nbsp;Xiu Zhang,&nbsp;Bo Hou,&nbsp;Xiao Wang,&nbsp;Mingyue Ma,&nbsp;Fu Ren","doi":"10.1002/jat.4728","DOIUrl":"10.1002/jat.4728","url":null,"abstract":"<div>\u0000 \u0000 <p>Ergothioneine (EGT) is a diet-derived natural sulfur-containing amino acid that exhibits strong anti-oxidant and anti-inflammation activities. Oxidative stress and chronic inflammatory injury are predominant pro-fibrogenic factors. Therefore, EGT may have therapeutic potential against liver fibrosis; however, its underlying mechanism is incompletely understood. This study aimed at investigating the protective effects of EGT on liver fibrosis based on metabonomics and network pharmacology. A mouse model of liver fibrosis was established by intraperitoneal injection with 40% CCl₄ solution (2 mL/kg, twice a week) and intragastric administration with EGT (5, 10 mg/kg/d) for six weeks. Results showed that EGT improved liver function by reducing serum levels of ALT (alanine aminotransferase), AST (aspartate aminotransferase), and TBIL (total bilirubin), and alleviated liver fibrosis by reducing LN (laminin) and HyP (hydroxyproline) levels, decreasing expressions of α-SMA (α-smooth muscle actin), Col-I (collagen type I), and Col-III (collagen type III), and improving pathological changes. EGT also significantly inhibited CCl₄-induced hepatic inflammation and TGF-β/Smads signaling pathway. Metabolomics identified six key metabolic pathways, such as purine metabolism, glycerophospholipid metabolism, and sphingolipid metabolism, and eight key metabolites, such as xanthine, guanine, ATP, phosphatidylcholine, and sphingosine. Network pharmacology analysis showed that IL-17, cAMP and NF-κB signaling pathways were potential key mechanisms. Integrated analysis revealed that PLA2G2A might be a potential target of EGT against liver fibrosis. EGT may inhibit the glycerophospholipid metabolism through PLA2G2A to inhibit the TGF-β/Smads signaling pathway, thereby alleviating fibrosis. The present study indicates that EGT may be considered a valid therapeutic strategy to regress liver fibrosis, and provides novel insights into the pharmacological mechanism of EGT against liver fibrosis.</p>\u0000 </div>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":"45 3","pages":"514-530"},"PeriodicalIF":2.7,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692974","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":"Behavioural, Teratogenic and Genotoxic Effects of Antibacterial Compounds, Triclocarban and Triclosan, in Hydra vulgaris","authors":"Aditya Mohan Menon,&nbsp;Gayathri R. Chandran,&nbsp;Vijayakumar Bommuraj,&nbsp;Babu Rajendran Ramaswamy,&nbsp;Thirumurugan Ramasamy","doi":"10.1002/jat.4730","DOIUrl":"10.1002/jat.4730","url":null,"abstract":"<div>\u0000 \u0000 <p>Triclocarban (TCC) and triclosan (TCS) are antibacterial compounds used in household, veterinary, industrial and personal care products, which are known to be environmental pollutants and also toxic to organisms. The toxicological effects of these antibacterial chemicals on higher organisms have been studied in detail. But in lower invertebrates like hydra, it is still rare and yet to be explored. In this study, the toxicological effects of these two antibacterial compounds in <i>Hydra vulgaris</i> was performed to clearly understand the organismal, developmental, molecular and behavioural changes. Both TCC and TCS are toxic with respective LC₅₀ values of 0.09 and 0.25 mg/L, whereas TCC is comparatively more toxic than TCS. The structural damage of battery cell complexes (BCCs) on the tentacles was observed and ultimately made prey capturing difficult. It was evident that TCC and TCS exposure caused developmental toxicity by affecting reproduction and regeneration in <i>H. vulgaris</i> at higher sublethal doses (0.045 and 0.125 mg/L, respectively). TCC and TCS also caused DNA damage resulting in apoptosis. This study further reveals that these two antibacterial compounds are teratogenic and genotoxic in the organisms.</p>\u0000 </div>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":"45 4","pages":"551-562"},"PeriodicalIF":2.7,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692973","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":"A Rapid Quantitative Assessment Method for Liver Damage Effects of Compounds Based on Zebrafish Liver Partition Area Ratio","authors":"Jing Yang,&nbsp;Jingcheng Zhao,&nbsp;Te Zheng,&nbsp;Jiashuo Zhou,&nbsp;Huiwen Zhang,&nbsp;Yun Zhang","doi":"10.1002/jat.4726","DOIUrl":"10.1002/jat.4726","url":null,"abstract":"<div>\u0000 \u0000 <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(<i>l-fabp</i>: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>\u0000 </div>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":"45 3","pages":"503-513"},"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,&nbsp;Josephine Lang,&nbsp;Magdalena-Sophie Picker,&nbsp;Angela Rossi,&nbsp;Christian Wilhelm,&nbsp;Armin von Fournier,&nbsp;Manuel Stöth,&nbsp;Miguel Goncalves,&nbsp;Norbert Kleinsasser,&nbsp;Stephan Hackenberg,&nbsp;Agmal Scherzad,&nbsp;Till Jasper Meyer","doi":"10.1002/jat.4717","DOIUrl":"10.1002/jat.4717","url":null,"abstract":"<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":"45 3","pages":"482-491"},"PeriodicalIF":2.7,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jat.4717","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":"OA","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,&nbsp;Siqi Zhao,&nbsp;Yuzhu Lei,&nbsp;Yunhua Hu,&nbsp;Yizhong Yan,&nbsp;Guanling Song","doi":"10.1002/jat.4725","DOIUrl":"10.1002/jat.4725","url":null,"abstract":"<div>\u0000 \u0000 <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>\u0000 </div>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":"45 3","pages":"492-502"},"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}