Journal of Applied Toxicology最新文献

{"title":"Pilot Study of Acute and Subchronic Oral Toxicological Biosafety Evaluation of Resorcinol-Formaldehyde Aerogel Nanomaterial in Kunming Mice.","authors":"Guangzhen Zheng, Yong Zhu, Bingmin Wu, Xiaoyuan Xu, Juanjuan Cheng, Yan Liu, Song Huang, Jing Chen, Qingping Xiong, Jihang Chen","doi":"10.1002/jat.4735","DOIUrl":"https://doi.org/10.1002/jat.4735","url":null,"abstract":"<p><p>Resorcinol-formaldehyde aerogel (RFa) is a unique nanomaterial composed of polymer nanoparticles with a three-dimensional network structure. Our previous studies have demonstrated its application in the separation and purification of alkaloids, and we are exploring its application potential as the drug delivery carrier. Therefore, it is necessary to comprehensively understand the in vivo toxicity profile of RFa and evaluate its oral biosafety. In this work, we systematically evaluated the in vivo acute toxicity and subchronic oral toxicity of RFa in both male and female Kunming mice. During the 14-day acute toxicity test, the dose administered (M = 580 mg/kg) was converted from the clinical dose of adsorbed alkaloids on RFa. The mice were gavaged only once and were observed continuously for 14 days. There were no abnormalities, and pathological changes in the major organs (heart, liver, spleen, lungs, kidneys, testes, and ovaries) were detected, followed by the 12-week subchronic toxicity test at the dose of 1/4M, 1/2M, and M. All mice were administered orally once daily and regularly observed throughout the experimental period. As a result, no abnormalities were found in body weights, food intake, and organ coefficients. Tissue section revealed no pathological changes in the major organs. In addition, there were no significant differences in hematological, blood biochemical, and coagulation parameters in both male and female mice compared to control group. These results showed that RFa was well tolerated at these dosage levels and did not cause significant toxic effects in Kunming mice. This study, as part of a broad research program on the biosafety of aerogel nanomaterials, provided the biosafety assurance for the subsequent study of RFa in biomedical applications.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142818160","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":"Toxicological Safety Assessment of Heat-Treated Lactiplantibacillus plantarum OLL2712 as a Food Ingredient","authors":"Ryan M. Parente,&nbsp;Takayuki Toshimitsu,&nbsp;Youko Nakamoto,&nbsp;Tomoyasu Taguchi","doi":"10.1002/jat.4723","DOIUrl":"10.1002/jat.4723","url":null,"abstract":"<div>\u0000 \u0000 <p><i>Lactiplantibacillus plantarum</i> is a Gram-positive, bacilli-shaped bacterium commonly found in fermented foods and the human gastrointestinal tract. Heat-treatment of <i>L. plantarum</i> OLL2712 prior to consumption has been found to have positive health effects. However, a full toxicological evaluation of heat-treated <i>L. plantarum</i> OLL2712 cells (heat-treated OLL2712) has not been conducted. In this regard, heat-treated OLL2712 was evaluated for use as an ingredient in food and dietary supplements using a panel of toxicological tests including genotoxic and subchronic studies. Heat-treated OLL2712 did not show any genotoxicity based on an in vitro mammalian chromosomal aberration test and in vivo mouse micronucleus assay up to 8.0 × 10⁹ cells/mL and 6.4 × 10¹² cells/kg, respectively. In the acute oral toxicity study, no toxic effects were observed at 5 × 10¹¹ cells/kg body weight. In the 13-week subchronic toxicity study, rats were administered (via gavage) heat-treated OLL2712 at concentrations of 0.5 × 10¹¹, 1.5 × 10¹¹, and 5 × 10¹¹ cells/kg body weight. Administration did not significantly impact mortality, body weight, food consumption, ophthalmology, hematology, clinical chemistry, coagulation, urinalysis, and macroscopic or microscopic findings. The no-observed-adverse-effect level of heat-treated OLL2712 in both sexes was 5 × 10¹¹ cells/kg body weight/day, the highest dose tested.</p>\u0000 </div>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":"45 4","pages":"694-710"},"PeriodicalIF":2.7,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813067","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":"Blockade of Voltage-Gated K+ Channels in Rabbit Coronary Arterial Smooth Muscle Cells by the Antipsychotic Drug Zotepine","authors":"Wenwen Zhuang,&nbsp;Minju Park,&nbsp;Junsu Jeong,&nbsp;Hye Ryung Kim,&nbsp;YeEun Jang,&nbsp;Hongzoo Park,&nbsp;Sunghun Na,&nbsp;Hongliang Li,&nbsp;Won Sun Park","doi":"10.1002/jat.4740","DOIUrl":"10.1002/jat.4740","url":null,"abstract":"<div>\u0000 \u0000 <p>Zotepine is a second-generation antipsychotic that demonstrates significant efficacy in antagonizing D₂ and 5-HT_2A receptors. Although clinical investigations have shown that administering zotepine is associated with an increased prevalence of hyperglycemia and a heightened risk of cardiovascular disease, the side effects of zotepine on voltage-gated K⁺ (Kv) channels have not been established. Zotepine suppressed the vascular Kv channels in rabbit coronary arterial smooth muscle cells in a concentration-dependent manner, with an IC₅₀ of 5.3 ± 0.4 μM and a Hill coefficient of 1.6 ± 0.2. The decay rate of inactivation was significantly accelerated by zotepine. Applying zotepine (10 μM) shifted the steady-state inactivation curve in a negative direction. Applying train pulses at 1 and 2 Hz resulted in a progressive increase in blockage of the Kv currents by zotepine. Furthermore, zotepine prolonged the recovery time from inactivation. Although pretreatment with the Kv2.1 subtype inhibitor stromatoxin-1 and the Kv7 subtype inhibitor linopirdine did not change the degree of zotepine-induced inhibition of Kv currents, pretreatment with the Kv1.5 channel inhibitor DPO-1 decreased the inhibitory effects of zotepine on Kv currents. Zotepine also induced membrane depolarization. These results indicate that zotepine inhibits Kv currents (mainly Kv1.5 subtype) in dose-, time-, and use (state)-dependent manners by changing the steady-state inactivation curve.</p>\u0000 </div>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":"45 4","pages":"685-693"},"PeriodicalIF":2.7,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142800307","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":"Behavioral Alterations in Mice Exposed to Manganese via Drinking Water: Effects of Sex and a Lipopolysaccharide Challenge","authors":"Helaina D. Ludwig,&nbsp;Jessica M. Carpenter,&nbsp;Nikolay M. Filipov","doi":"10.1002/jat.4739","DOIUrl":"10.1002/jat.4739","url":null,"abstract":"<p>Manganese (Mn) is an essential and important metal; however, overexposures lead to adverse neurological outcomes. Nonoccupational Mn overexposure occurs primarily through consumption of Mn-contaminated drinking water (DW). Sex differences in terms of nervous and immune systems' responsiveness to excessive Mn in the DW are understudied. Thus, this study investigated behavioral and sex differences in response to Mn DW treatment (0.4 g Mn/L for up to 8 weeks) and a lipopolysaccharide (LPS) challenge of adult C57BL/6 mice with GFP-tagged monocytes/microglia. After 6 weeks, in motor function tests, Mn exposure resulted in decreased activity and gait deficits. In two different mood tests (open field test [OFT]/elevated zero maze), Mn-exposed mice exhibited decreased fear/anxiety-like behavior. Two weeks after behavioral assessment, when mice were challenged with LPS, circulating inflammatory cytokines, and acute phase proteins increased in both sexes. After 8 weeks of Mn exposure, liver and brain Mn levels were increased, but Mn alone did not affect circulating cytokines in either sex. Notably, Mn-exposed/LPS-challenged males had potentiated plasma cytokine output, whereas the reverse was seen in females. Males, but not females, continued to exhibit increased fearlessness (i.e., increased OFT center time), even when challenged with LPS. Overall, our results show that Mn DW exposure increases brain Mn levels and it leads to behavioral alterations in both sexes. However, males might be more susceptible to the effect of Mn on mood, and this effect is recalcitrant to an inflammagen challenge. Mn augmented post-LPS cytokine production only in males, further indicating that important Mn effects are sex-biased.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":"45 4","pages":"669-684"},"PeriodicalIF":2.7,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jat.4739","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794831","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":"Evaluation of the Neuroprotective Effects of Idebenone in an Experimental Carbon Monoxide Poisoning Model","authors":"Hulya Karakus,&nbsp;Ozlem Bulbul,&nbsp;Ali Kulaber,&nbsp;Huseyin Yaman,&nbsp;Sinan Pasli,&nbsp;Melih Imamoglu,&nbsp;Yunus Karaca,&nbsp;Engin Yenilmez,&nbsp;Vildan Ozer","doi":"10.1002/jat.4742","DOIUrl":"10.1002/jat.4742","url":null,"abstract":"<div>\u0000 \u0000 <p>Carbon monoxide (CO) poisoning is among the main causes of poisoning-related mortality and morbidity, primarily affecting the central nervous system and leading to delayed neurological sequelae. Idebenone exerts antioxidant and neuroprotective effects. In this study, we aimed to evaluate the specific neuroprotective effects of idebenone against CO poisoning. Forty female Wistar Albino rats were used in this study. Except the controls, the other rats inhaled 5000 ppm CO until a change in consciousness was observed. Rats with carboxyhemoglobin concentrations over 20% in blood samples collected from the tail vein were considered successful acute CO poisoning models. The rats were divided into five groups: healthy control (HC; group 1), CO + saline (CO-S; group 2), CO + 100 mg/kg idebenone (CO-I₁₀₀; group 3), CO + 200 mg/kg idebenone (CO-I₂₀₀; group 4), and CO + 300 mg/kg idebenone (CO-I₃₀₀; group 5). Pre-determined doses of idebenon were orally administered to the rats at 24-h intervals for 5 days. The rats were anesthetized and sacrificed 24 h after the last drug dose. Histopathological and biochemical parameters were examined in the blood and hippocampus samples of the rats. Histopathological grading of neurons in the hippocampus revealed that the CO-S group exhibited the highest number of grade 1, 2, and 3 degenerative cells (all <i>p</i> = 0.001). Apoptotic index was the highest in the CO-S group and significantly low in the idebenone-treated groups (<i>p</i> = 0.001). Neuron-specific enolase and malondialdehyde levels and oxidative stress index were significantly lower in both the hippocampus and serum samples of the idebenone-treated groups than in those of the CO-S group (all <i>p</i> values = 0.001). Overall, idebenone inhibited degeneration due to CO-induced brain damage and exerted neuroprotective effects against oxidative stress in rats.</p>\u0000 </div>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":"45 4","pages":"659-668"},"PeriodicalIF":2.7,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142785599","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":"Ninety-Day Feeding Test of Stacked DBN9936 × DBN9501 Maize on Sprague Dawley Rats","authors":"Yan Li,&nbsp;Chao Han,&nbsp;Lili Shi,&nbsp;Chen Chen,&nbsp;Jinpeng Zhao,&nbsp;Tingting Liu,&nbsp;Qin Zhuo","doi":"10.1002/jat.4733","DOIUrl":"10.1002/jat.4733","url":null,"abstract":"<div>\u0000 \u0000 <p>The transgenic maize DBN9936 × DBN9501, which confers resistance to insects and tolerance to herbicides, was developed via conventional cross breeding of transgenic maize DBN9936 and DBN9501. In our present study, a 90-day feeding toxicity study was conducted on Sprague Dawley rats to evaluate the safety of the maize. A total of 140 rats were randomly assigned to seven groups (<i>n</i> = 10/sex/group): one control group, three genetically modified (GM) groups with 17.5%, 35%, and 70% (wt/wt) GM maize, respectively, and three non-GM groups with corresponding incorporation rate of parental maize DBN318. The rats of control group were fed with AIN93G diet. The parameters including body weights, food consumption, hematology, serum biochemistry, organ weights, and histopathology were examined during the course of the study. Compared with the non-GM group or AIN93G control group, minor statistical differences were observed for some parameters in some groups, yet none of them was considered a GM-related adverse effect. In conclusion, the results demonstrated that no adverse effect was observed on rats following 90 days feeding with diet containing up to 70% GM maize. The results indicated that stacked maize DBN9936 × DBN9501 was as safe as its parental DBN318 maize.</p>\u0000 </div>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":"45 4","pages":"646-658"},"PeriodicalIF":2.7,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142785608","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":"Butorphanol Alleviates Hypoxia/Reoxygenation-Induced Myocardial Injury by Activating Wnt/β-Catenin Signal Pathway","authors":"Shi-Rui Hao,&nbsp;Zi-Feng Xie,&nbsp;Jia-Xin Li,&nbsp;Qin-Zhi Wang,&nbsp;Ting-Ting Wu,&nbsp;Tu Shen,&nbsp;Qiao-Ling Wu","doi":"10.1002/jat.4736","DOIUrl":"10.1002/jat.4736","url":null,"abstract":"<div>\u0000 \u0000 <p>Ischemic heart disease remains a global health problem with high morbidity and mortality. Butorphanol, as a novel opioid, has been discovered with its cardioprotective properties. The purpose of this study was to explore that butorphanol can alleviate hypoxia/reoxygenation (H/R)-induced myocardial injury by activating the Wnt/β-catenin signal pathway. In this study, Cell Counting Kit-8 (CCK-8), lactate dehydrogenase (LDH) kit, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, and Western blotting experiments were performed to observe butorphanol cardioprotective function and expression of Wnt signaling pathway proteins. For the main result, anti-apoptotic effect and higher expression of Wnt signaling pathway proteins were observed with the increasing concentrations of butorphanol. Compared with the H/R group, higher cellular viability, lower LDH release, and smaller apoptotic cell population were found in the butorphanol group. In addition, expression levels of apoptosis-related protein Bax and Cleaved Caspase-3 decreased, and increased expression of Bcl-2 were observed. Conversely, the protective effects of butorphanol were attenuated in the XAV939 group. In summary, butorphanol attenuates hypoxia/reoxygenation-induced myocardial injury by activating the Wnt/β-catenin signal pathway. Our work provides a theoretical basis for butorphanol's myocardial protective function.</p>\u0000 </div>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":"45 4","pages":"636-645"},"PeriodicalIF":2.7,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142769367","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":"Skin Sensitization Potency Prediction Based on Read-Across (RAx) Incorporating RhE-Based Testing Strategy (RTSv1)–Defined Approach: RTSv1-Based RAx","authors":"Sho Suzuki,&nbsp;Hideyuki Mizumachi,&nbsp;Masaaki Miyazawa","doi":"10.1002/jat.4737","DOIUrl":"10.1002/jat.4737","url":null,"abstract":"<div>\u0000 \u0000 <p>In recent years, nonanimal approaches for skin sensitization have been developed in response to political, regulatory, and ethical demands. The reconstructed human epidermis (RhE)–based testing strategy (RTS)v1–defined approach (DA) is used to categorize skin sensitization potency. However, the RTSv1 DA alone cannot be used to predict potency based on EC3 values [the estimated concentration that produces a stimulation index of 3 in the local lymph node assay (LLNA)], and underpredictions have been reported. Read-across (RAx) can complement DA data and improve prediction confidence. Although case studies combining new approach methodology/DA data with RAx have been reported, they focus on a single target chemical and lack a comprehensive and robust strategy with well-examined reliability. This study developed a strategy incorporating the RTSv1 DA into RAx (RTSv1-based RAx) to predict skin sensitization potency, applying it to 43 chemicals. The predictive performance of RTSv1-based RAx was evaluated by comparing its predicted potency category and EC3 outcomes with those of RTSv1 DA and the LLNA. RTSv1-based RAx accurately predicted the Globally Harmonized System of Classification (GHS) subcategorization for 38 chemicals and determined the predicted EC3 values for 17 sensitizers within a fourfold range of LLNA-derived EC3 values. This study demonstrates that RTSv1-based RAx offers robust predictivity for both GHS subcategorization and predicted EC3 values, making it useful for quantitative risk assessment.</p>\u0000 </div>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":"45 4","pages":"620-635"},"PeriodicalIF":2.7,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142769299","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 Proinflammatory Cytokine Activity at Different Levels of Fluoride Exposure: A Systematic Review.","authors":"Jesús Lavalle-Carrasco, Nelly Molina-Frechero, Sandra López-Verdín, Ronell Bologna-Molina","doi":"10.1002/jat.4734","DOIUrl":"https://doi.org/10.1002/jat.4734","url":null,"abstract":"<p><p>The chronic intake of excessive fluoride (F^-) (>  1.5 mg/L) affects several tissues, organs, and systems. This represents a worldwide issue due to the presence of the compound in nature, with drinking water being the main source of exposure. The underlying mechanisms by which F^- is toxic are not completely understood, but proinflammatory cytokine activity is implicated in these events. The aim of this study was to perform a systematic review of the health implications of proinflammatory cytokine activity at different levels of F^- exposure. The search for original studies in which the activity of proinflammatory cytokines was assessed under exposure to F^- was performed using the PubMed, Scopus, Springer, EBSCO, and Google Scholar databases by applying the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. The study protocol was registered with PROSPERO (CRD42024546726). Sixteen studies were analyzed in the present review. Tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1 beta (β), IL-6, IL-2, IL-12, IL-17, IL-18, C-reactive protein, and transforming growth factor-β (TGF-β) were the proinflammatory cytokines identified in the included reports. Alterations in cytokine activity were observed in response to varying levels of F^- exposure, implicating an increased risk of toxicity and damage to the evaluated structures by highlighting the role of inflammation in the progression of these processes. Hence, the activity of proinflammatory cytokines at different levels of F^- exposure has important implications for health, where inflammation plays a relevant role in the underlying mechanisms related to the resulting toxicity.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142769298","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":"Arenobufagin Induces Ferroptosis in Glioblastoma Cells via Modulating the MiR-149-5p/AEBP1 Axis","authors":"Renzhi Hu,&nbsp;Sisi Tang,&nbsp;Yanrui Xiang,&nbsp;Shuyong Qin","doi":"10.1002/jat.4732","DOIUrl":"10.1002/jat.4732","url":null,"abstract":"<div>\u0000 \u0000 <p>Accumulating evidences have proved Arenobufagin (ArBu) exhibited cytotoxic effects to multiple types of cancer. However, in glwioblastoma (GBM), which is easy to develop resistance to classic chemotherapy reagent, the therapeutic effects of ArBu have not been explored. In the current study, we found that GBM cells were sensitive to ArBu treatment and ArBu induced cell death both in a dose-dependent and a time-dependent manner. ArBu was observed to promote ROS accumulating and elevate Fe²⁺/MDA/GSH level, which lead to ferroptosis. Mechanistically, ArBu significantly downregulated AEBP1 expression and decreased the mRNA stability of AEBP1 without affecting its transcription. Then, AEBP1 mRNA was predicted to bind with miR-149-5p in GBM cells, which directly target its 3′UTR. At last, we found ArBu could upregulate miR-149-5p to suppress AEBP1 expression, and the rescue experiments confirmed miR-149-5p/AEBP1 axis regulated ferroptosis, which underlay the therapeutic effects of ArBu in GBM cells. This study revealed that ArBu induced ferroptosis in a dose-dependent manner via modulating miR-149-5p/AEBP1 axis. It provides evidences for clinical application of ArBu for GBM.</p>\u0000 </div>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":"45 4","pages":"606-619"},"PeriodicalIF":2.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142769363","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}