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Chronic exposure to B[a]P induces malignant transformation of breast epithelial cells through the mechanism via TGF-β signaling pathway. 慢性暴露于B[a]P可通过TGF-β信号通路诱导乳腺上皮细胞恶性转化。
IF 3.9 3区 医学
Food and Chemical Toxicology Pub Date : 2025-05-24 DOI: 10.1016/j.fct.2025.115574
Yongjun Tang, Zhengning Feng, Chenlu Ma, Nian Jang, Xiaolong Chen, Yingxu He, Francis L Martin, Hui Liu, Weiyi Pang
{"title":"Chronic exposure to B[a]P induces malignant transformation of breast epithelial cells through the mechanism via TGF-β signaling pathway.","authors":"Yongjun Tang, Zhengning Feng, Chenlu Ma, Nian Jang, Xiaolong Chen, Yingxu He, Francis L Martin, Hui Liu, Weiyi Pang","doi":"10.1016/j.fct.2025.115574","DOIUrl":"https://doi.org/10.1016/j.fct.2025.115574","url":null,"abstract":"<p><p>Breast cancer has a high global incidence, and benzo[a]pyrene (B[a]P) is considered a contributing factor that increases carcinogenic risk. This study examined B[a]P's oncogenic mechanisms in mammary epithelial cells. Chronic B[a]P exposure induced morphological changes and enhanced proliferative/clonogenic capacity in MCF-10A cells. Chronic B[a]P exposure altered gene expression in MCF-10A cells, revealing differential levels of circRNAs, lncRNAs, miRNAs, and mRNAs. qRT-PCR validation demonstrated strong alignment with RNA-seq results, ensuring sequencing reliability. Additionally, chronic B[a]P exposure upregulated the protein expression of AhR and ARNT, as well as TGF-β, pSmad2/3, and KRT14, while increasing Vimentin expression and decreasing E-cadherin expression. Notably, treatment with the TGF-β inhibitor SB431542 reversed these protein expression changes in transformed cells. These results show that exposure to Chronic B[a]P induces MCF-10A cell transformation. The underlying mechanisms involve significant transcriptional alterations, AhR/ARNT expression regulation, TGF-β signaling pathway activation, KRT14 protein modulation, and EMT. Furthermore, Chronic B[a]P exposure may drive transformation through TGF-β modulation. Chronic B[a]P exposure promotes breast carcinogenesis, revealing mechanistic insights and potential preventive biomarkers.</p>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":" ","pages":"115574"},"PeriodicalIF":3.9,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144148742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
RIFM fragrance ingredient safety assessment, phenyl salicylate, CAS Registry Number 118-55-8. 香料成分安全性评价,水杨酸苯酯,CAS登记号118-55-8。
IF 3.9 3区 医学
Food and Chemical Toxicology Pub Date : 2025-05-22 DOI: 10.1016/j.fct.2025.115565
A M Api, A Bartlett, D Belsito, D Botelho, M Bruze, A Bryant-Friedrich, G A Burton, M A Cancellieri, H Chon, M Cronin, S Crotty, M L Dagli, W Dekant, C Deodhar, K Farrell, A D Fryer, L Jones, K Joshi, A Lapczynski, D L Laskin, M Lavelle, I Lee, H Moustakas, J Muldoon, T M Penning, A H Piersma, G Ritacco, N Sadekar, I Schember, T W Schultz, F Siddiqi, I G Sipes, G Sullivan, Y Thakkar
{"title":"RIFM fragrance ingredient safety assessment, phenyl salicylate, CAS Registry Number 118-55-8.","authors":"A M Api, A Bartlett, D Belsito, D Botelho, M Bruze, A Bryant-Friedrich, G A Burton, M A Cancellieri, H Chon, M Cronin, S Crotty, M L Dagli, W Dekant, C Deodhar, K Farrell, A D Fryer, L Jones, K Joshi, A Lapczynski, D L Laskin, M Lavelle, I Lee, H Moustakas, J Muldoon, T M Penning, A H Piersma, G Ritacco, N Sadekar, I Schember, T W Schultz, F Siddiqi, I G Sipes, G Sullivan, Y Thakkar","doi":"10.1016/j.fct.2025.115565","DOIUrl":"https://doi.org/10.1016/j.fct.2025.115565","url":null,"abstract":"","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":" ","pages":"115565"},"PeriodicalIF":3.9,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144140980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Active compounds of licorice ameliorate microplastics-induced intestinal damage by targeting FADD 甘草活性化合物通过靶向FADD改善微塑料诱导的肠道损伤
IF 3.9 3区 医学
Food and Chemical Toxicology Pub Date : 2025-05-22 DOI: 10.1016/j.fct.2025.115570
Wen Xue, Xiuhe Fan, Yujing Hui, Jingao Yu
{"title":"Active compounds of licorice ameliorate microplastics-induced intestinal damage by targeting FADD","authors":"Wen Xue,&nbsp;Xiuhe Fan,&nbsp;Yujing Hui,&nbsp;Jingao Yu","doi":"10.1016/j.fct.2025.115570","DOIUrl":"10.1016/j.fct.2025.115570","url":null,"abstract":"<div><div>Microplastics (MPs), as a novel type of environmental pollutant, have the potential to impact human health. This study aims to investigate the protective efficacy of active compounds in licorice on microplastics-injured rats and reveal the underlying mechanisms. The MPs-injured rat model was established by orally administrated with MPs. After the treatment with different doses of a combination of liquiritigenin, isoliquiritigenin and glycyrrhetinic acid, the tissue injury, oxidative stress, inflammation and expressions of tight junction proteins in colon and liver were evaluated. Our data showed that active compounds of licorice significantly ameliorate colonic and liver damage caused by MPs, improving function colonic barrier and liver function, reducing oxidative stress and systemic inflammatory factors. Then, a total of 29 differentially expressed proteins were identified by label-free proteomics analysis, among which the down-regulated Fas-associating protein with a novel death domain (FADD) was found to be the most related with the protective effects of licorice. What’s more, this protein target also interacts directly with active compounds of licorice, through hydrogen bounds and hydrophobic interactions involving 11 residues. This study suggested that licorice exerts protective effects against MPs on rats, through down-regulating as well as directly interacting with FADD.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"203 ","pages":"Article 115570"},"PeriodicalIF":3.9,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144138076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Fucoxanthin restores mitochondrial bioenergetics and attenuates dexamethasone-induced osteoblast Dysfunction: Implications for glucocorticoid-associated bone disorders 岩藻黄素恢复线粒体生物能量和减轻地塞米松诱导的成骨细胞功能障碍:糖皮质激素相关骨疾病的意义
IF 3.9 3区 医学
Food and Chemical Toxicology Pub Date : 2025-05-22 DOI: 10.1016/j.fct.2025.115573
Ekramy M. Elmorsy , Ayat B. Al-Ghafari , Huda A. Al Doghaither , Ruba O. Almaghrabi , Samah F. Ibrahim , Gamal Othman , Ateya M. Ibrahim , Ahmed Abdeen
{"title":"Fucoxanthin restores mitochondrial bioenergetics and attenuates dexamethasone-induced osteoblast Dysfunction: Implications for glucocorticoid-associated bone disorders","authors":"Ekramy M. Elmorsy ,&nbsp;Ayat B. Al-Ghafari ,&nbsp;Huda A. Al Doghaither ,&nbsp;Ruba O. Almaghrabi ,&nbsp;Samah F. Ibrahim ,&nbsp;Gamal Othman ,&nbsp;Ateya M. Ibrahim ,&nbsp;Ahmed Abdeen","doi":"10.1016/j.fct.2025.115573","DOIUrl":"10.1016/j.fct.2025.115573","url":null,"abstract":"<div><div>Dexamethasone (DEX), a widely used anti-inflammatory glucocorticoid, is associated with bone-related adverse effects. This study investigated the protective role of fucoxanthin (FX), a bioactive carotenoid, against DEX-induced bioenergetic disruption in human osteoblasts. DEX reduced osteoblast viability (48 h EC<sub>50</sub> = 20 μM), which FX (10–20 μM) counteracted. DEX (2–20 μM) impaired osteoblast function, marked by decreased secretion of procollagen type I, osteocalcin, and alkaline phosphatase, alongside reduced ATP levels, mitochondrial membrane potential (MMP), and oxygen consumption (OC). DEX also elevated lactate production, suppressed mitochondrial complexes I and III activities, and downregulated mitochondrial gene expressions (ND1, ND5, cytochrome <em>b</em>, cytochrome <em>c</em> oxidase, ATP synthase subunits 6/8). Additionally, DEX increased mitochondrial membrane fluidity, swelling, and H<sup>+</sup>/K<sup>+</sup> permeability. FX attenuated these effects dose-dependently, restoring viability, secretory function, and bioenergetic parameters (ATP, MMP, OC) while mitigating mitochondrial structural and ionic disturbances. These findings highlight FX's potential to alleviate DEX-induced osteoblast dysfunction by preserving mitochondrial integrity and bioenergetics, suggesting its therapeutic utility in managing glucocorticoid-associated bone disorders.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"203 ","pages":"Article 115573"},"PeriodicalIF":3.9,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144138075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Comparative detection of E. coli, B. subtilis and their mixture in yam samples by ATP bioluminescence and SERS methods ATP生物发光法和SERS法比较检测山药样品中的大肠杆菌、枯草芽孢杆菌及其混合物。
IF 3.9 3区 医学
Food and Chemical Toxicology Pub Date : 2025-05-21 DOI: 10.1016/j.fct.2025.115569
Maomei Xie , Zeshuai Zhang , Shiyu Gao , Yueling Yan , Yidan Liu , Wenbo Wu , Liyi Deng , Yuefei Wang , Zheng Li , Haixia Wang
{"title":"Comparative detection of E. coli, B. subtilis and their mixture in yam samples by ATP bioluminescence and SERS methods","authors":"Maomei Xie ,&nbsp;Zeshuai Zhang ,&nbsp;Shiyu Gao ,&nbsp;Yueling Yan ,&nbsp;Yidan Liu ,&nbsp;Wenbo Wu ,&nbsp;Liyi Deng ,&nbsp;Yuefei Wang ,&nbsp;Zheng Li ,&nbsp;Haixia Wang","doi":"10.1016/j.fct.2025.115569","DOIUrl":"10.1016/j.fct.2025.115569","url":null,"abstract":"<div><div>Pathogenic bacteria rapid detection is important to ensure food safety and human health. In this study, surface-enhanced Raman spectroscopy (SERS) and adenosine triphosphate bioluminescence (ATP-BL) optical detection platforms were established for evaluating and comparing the performance in the detection of <em>E. coli</em>, <em>B. subtilis</em> and their mixture in yam slices. The results showed that the two techniques significantly reduced the time and cost compared with the traditional culture method. Among them, the detection limits based on SERS were 8.64 CFU/mL, 6.11 CFU/mL and 11.22 CFU/mL for <em>E. coli, B. subtilis</em> and mixed bacteria in actual yam slices, respectively. Accordingly, the detection limits based on ATP-BL were 49.58 CFU/mL, 50.63 CFU/mL and 26.01 CFU/mL, respectively, which demonstrated that both techniques possessed excellent sensitivity and reliability. The results of statistical analysis by <em>t</em>-tests showed that there was no significant difference (<em>P</em> &gt; 0.05) between the two methods and the plate culture method, and the recovery rates were both between 85 %–115 %. In addition, compared to the constructed ATP-BL platform, the SERS method had higher stability, lower detection limit, and shorter time consumption.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"203 ","pages":"Article 115569"},"PeriodicalIF":3.9,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144132050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Update to RIFM fragrance ingredient safety assessment, phenethyl acetate, CAS Registry Number 103-45-7. 更新RIFM香料成分安全性评估,醋酸苯乙酯,CAS注册号103-45-7。
IF 3.9 3区 医学
Food and Chemical Toxicology Pub Date : 2025-05-21 DOI: 10.1016/j.fct.2025.115564
A M Api, A Bartlett, D Belsito, D Botelho, M Bruze, A Bryant-Friedrich, G A Burton, M A Cancellieri, H Chon, M Cronin, S Crotty, M L Dagli, W Dekant, C Deodhar, K Farrell, A D Fryer, L Jones, K Joshi, A Lapczynski, D L Laskin, M Lavelle, I Lee, H Moustakas, J Muldoon, T M Penning, A H Piersma, G Ritacco, N Sadekar, I Schember, T W Schultz, F Siddiqi, I G Sipes, G Sullivan, Y Thakkar
{"title":"Update to RIFM fragrance ingredient safety assessment, phenethyl acetate, CAS Registry Number 103-45-7.","authors":"A M Api, A Bartlett, D Belsito, D Botelho, M Bruze, A Bryant-Friedrich, G A Burton, M A Cancellieri, H Chon, M Cronin, S Crotty, M L Dagli, W Dekant, C Deodhar, K Farrell, A D Fryer, L Jones, K Joshi, A Lapczynski, D L Laskin, M Lavelle, I Lee, H Moustakas, J Muldoon, T M Penning, A H Piersma, G Ritacco, N Sadekar, I Schember, T W Schultz, F Siddiqi, I G Sipes, G Sullivan, Y Thakkar","doi":"10.1016/j.fct.2025.115564","DOIUrl":"https://doi.org/10.1016/j.fct.2025.115564","url":null,"abstract":"","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":" ","pages":"115564"},"PeriodicalIF":3.9,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144132087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Millettia speciosa Champ. root extracts relieve exhaustive fatigue by regulating gut microbiota in mice 香槟酒。根提取物通过调节小鼠肠道微生物群来缓解穷尽性疲劳。
IF 3.9 3区 医学
Food and Chemical Toxicology Pub Date : 2025-05-21 DOI: 10.1016/j.fct.2025.115557
Xinru Hu, Zhen Zhong, Longhui Yu, Qinru Yang, Jinfeng Zhang, Wenjing Wang, Peiqin Chen, Jingen Li, Guodong Zheng
{"title":"Millettia speciosa Champ. root extracts relieve exhaustive fatigue by regulating gut microbiota in mice","authors":"Xinru Hu,&nbsp;Zhen Zhong,&nbsp;Longhui Yu,&nbsp;Qinru Yang,&nbsp;Jinfeng Zhang,&nbsp;Wenjing Wang,&nbsp;Peiqin Chen,&nbsp;Jingen Li,&nbsp;Guodong Zheng","doi":"10.1016/j.fct.2025.115557","DOIUrl":"10.1016/j.fct.2025.115557","url":null,"abstract":"<div><h3>Background</h3><div>Exhaustive fatigue (EF) has become a common concern, and using natural active ingredients as prebiotics has become prospective strategy for fatigue alleviation. <em>Millettia speciosa</em> Champ. root (MS) has anti-fatigue activity, but the relationship between MS anti-fatigue effect and gut microbiota remains unclear.</div></div><div><h3>Purpose</h3><div>To investigate the relationship between anti-fatigue effect of MS extracts and gut microbiota.</div></div><div><h3>Methods</h3><div>MS was extracted with water and ethanol to obtain MS water extract (MSW) and MS ethanol extract (MSE). Sixty ICR mice were divided into six groups: Control, American ginseng<u>,</u> low-, high-doses MSW and low-, high-doses MSE for 28 days. Fatigue related biochemical indexes and gut microbiota of cecum contents were analyzed.</div></div><div><h3>Results</h3><div>MSW and MSE effectively prolonged swimming time and climbing time in mice, decreased harmful metabolites, increased the glycogen content in the liver and muscle, and reduced oxidative stress damage. Furthermore, the dysbiosis of gut microbiota induced by EF was restored by MSW and MSE, including enriching beneficial bacteria and depleting harmful bacteria.</div></div><div><h3>Conclusion</h3><div>The results suggested that MS extracts may effectively alleviate EF though improving exercise endurance, reducing oxidative stress and regulating gut microbiota homeostasis in mice. Therefore, MS extracts may be considered as a prebiotic agent to improve EF.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"203 ","pages":"Article 115557"},"PeriodicalIF":3.9,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144132085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Update to RIFM fragrance ingredient safety assessment, fenchone, CAS Registry Number 1195-79-5. 更新RIFM香料成分安全评估,fenchone, CAS注册号1195-79-5
IF 3.9 3区 医学
Food and Chemical Toxicology Pub Date : 2025-05-21 DOI: 10.1016/j.fct.2025.115562
A M Api, A Bartlett, D Belsito, D Botelho, M Bruze, A Bryant-Friedrich, G A Burton, M A Cancellieri, H Chon, M Cronin, S Crotty, M L Dagli, W Dekant, C Deodhar, K Farrell, A D Fryer, L Jones, K Joshi, A Lapczynski, D L Laskin, M Lavelle, I Lee, H Moustakas, J Muldoon, T M Penning, A H Piersma, G Ritacco, N Sadekar, I Schember, T W Schultz, F Siddiqi, I G Sipes, G Sullivan, Y Thakkar
{"title":"Update to RIFM fragrance ingredient safety assessment, fenchone, CAS Registry Number 1195-79-5.","authors":"A M Api, A Bartlett, D Belsito, D Botelho, M Bruze, A Bryant-Friedrich, G A Burton, M A Cancellieri, H Chon, M Cronin, S Crotty, M L Dagli, W Dekant, C Deodhar, K Farrell, A D Fryer, L Jones, K Joshi, A Lapczynski, D L Laskin, M Lavelle, I Lee, H Moustakas, J Muldoon, T M Penning, A H Piersma, G Ritacco, N Sadekar, I Schember, T W Schultz, F Siddiqi, I G Sipes, G Sullivan, Y Thakkar","doi":"10.1016/j.fct.2025.115562","DOIUrl":"https://doi.org/10.1016/j.fct.2025.115562","url":null,"abstract":"","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":" ","pages":"115562"},"PeriodicalIF":3.9,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144132086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Ferroptosis effects and behavioral changes associated with high accumulation and low elimination percentage of silver in brain following a 28-day nasal instillation of silver nanoparticles in mice 经鼻注射银纳米颗粒28天后,小鼠脑内银的高蓄积和低消除率与铁下垂效应和行为改变相关
IF 3.9 3区 医学
Food and Chemical Toxicology Pub Date : 2025-05-21 DOI: 10.1016/j.fct.2025.115567
Shuyan Niu, Menghao Guo, Haitao Yang, Xiaoru Chang, Mengting Shang, Liqing Wu, Yu Ma, Yuying Xue
{"title":"Ferroptosis effects and behavioral changes associated with high accumulation and low elimination percentage of silver in brain following a 28-day nasal instillation of silver nanoparticles in mice","authors":"Shuyan Niu,&nbsp;Menghao Guo,&nbsp;Haitao Yang,&nbsp;Xiaoru Chang,&nbsp;Mengting Shang,&nbsp;Liqing Wu,&nbsp;Yu Ma,&nbsp;Yuying Xue","doi":"10.1016/j.fct.2025.115567","DOIUrl":"10.1016/j.fct.2025.115567","url":null,"abstract":"<div><div>This study investigates the ferroptosis effects and behavioral changes in mice following 28-day nasal instillation of silver nanoparticles (AgNPs, 0–50 mg/kg.bw), with subsequent observation of recovery effects over a 28-day period. AgNP accumulates differentially in the organs evaluated. However, the hippocampus was an important target. Spatial learning and memory deficits were detected using the Morris Water Maze. Hippocampal neuronal damage was observed, characterized by loss of cellular integrity, cytoplasmic atrophy, and blurred nuclei. These alterations persisted throughout the 28-day recovery period. Lipid peroxidation was triggered by depletion of GSH and elevation of MDA. Disruption of iron homeostasis was mediated through downregulation of TFRC, FTH1, and FTL protein expression. Ferroptosis activation was confirmed by suppression of GPX4 and SLC7A11, coupled with upregulation of ACSL4 and COX2. Additionally, exposure to Ag<sup>+</sup> in the amount released from AgNPs (50 mg/kg) also resulted in sustained silver accumulation and ferroptosis effects. Beyond nanoparticle-specific toxicity, the study emphasizes the potential adverse effects resulting from the prolonged and gradual release of metal ions from these nanoparticles <em>in vivo</em>. Our study provided experimental evidence and potential clues into the neurotoxicity of metal nanoparticles.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"202 ","pages":"Article 115567"},"PeriodicalIF":3.9,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144116933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Activation of Rab7-mediated lipophagy is required for triptolide to induce ferroptosis in hepatic cells 雷公藤甲素诱导肝细胞铁下垂需要激活rab7介导的脂噬。
IF 3.9 3区 医学
Food and Chemical Toxicology Pub Date : 2025-05-20 DOI: 10.1016/j.fct.2025.115568
Shan Liu , Yuerui Su , Bo Han , Liang Yin , Huifang Li , Yingli Wang , Kun Zhou , Pengcheng Li , Yanming Wei
{"title":"Activation of Rab7-mediated lipophagy is required for triptolide to induce ferroptosis in hepatic cells","authors":"Shan Liu ,&nbsp;Yuerui Su ,&nbsp;Bo Han ,&nbsp;Liang Yin ,&nbsp;Huifang Li ,&nbsp;Yingli Wang ,&nbsp;Kun Zhou ,&nbsp;Pengcheng Li ,&nbsp;Yanming Wei","doi":"10.1016/j.fct.2025.115568","DOIUrl":"10.1016/j.fct.2025.115568","url":null,"abstract":"<div><div>The aim of this study was to investigate the regulation of triptolide on Rab7-mediated lipophagy to elucidate the potential association between lipophagy and ferroptosis in triptolide-induced hepatotoxicity. Human normal liver HL7702 cells and C57BL/6J mice were treated with triptolide to establish in vitro and in vivo models. The results revealed that triptolide caused a severe hepatic cell damage in vitro and in vivo. Concurrently, triptolide induced the remarkable activation of Rab7-mediated lipophagy, as evidenced by the decreased levels of lipid droplets and p62, the increased Rab7, microtubule-associated protein light chain 3Ⅱ (LC3Ⅱ) and phosphorylated adenosine monophosphate-activated protein kinase (AMPK) levels, as well as the increased colocalization of LC3 and Rab7 proteins. Moreover, triptolide obviously increased the levels of ferroptotic markers, including MDA, iron, prostaglandin endoperoxide synthase 2, and induced GSH and GPX4 exhaustion and oxidative stress in hepatic cells. Importantly, the inhibition of lipophagy mitigated ferroptosis and alleviated the hepatic cell damage induced by triptolide. our results demonstrated that triptolide-activated lipophagy with Rab7 serves as a pivotal factor in triggering ferroptosis and exacerbating hepatoxicity. The manipulation of lipophagy is thus a potential therapeutic strategy for ameliorating triptolide-induced hepatotoxicity.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"203 ","pages":"Article 115568"},"PeriodicalIF":3.9,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
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