{"title":"Mechanisms of LPS-induced toxicity in endothelial cells and the protective role of geniposidic acid","authors":"Yan Fang , He Meng , Jun Wang","doi":"10.1016/j.fct.2025.115488","DOIUrl":"10.1016/j.fct.2025.115488","url":null,"abstract":"<div><div>Vascular inflammation and oxidative stress are critical pathogenic factors in cardiovascular diseases. Lipopolysaccharide (LPS)-induced endothelial cytotoxicity, driven by oxidative stress and inflammation, remains incompletely understood. This study highlights the molecular mechanisms underlying LPS toxicity, focusing on the ROS/JNK/NLRP3 signaling axis. LPS disrupts mitochondrial function, increases ROS accumulation, activates JNK phosphorylation, and induces NLRP3 inflammasome activation, culminating in pyroptosis through caspase-1-mediated GSDMD cleavage. Mechanistic studies with the JNK inhibitor SP600125 confirmed the critical role of the ROS/JNK/NLRP3 pathway in LPS-induced endothelial damage. Additionally, PGC-1α, a key regulator of mitochondrial homeostasis, was identified as a protective factor suppressed by LPS, exacerbating ROS overproduction and inflammasome activation. To validate these findings, geniposidic acid (GPA), a natural antioxidant and anti-inflammatory compound, was employed. GPA effectively reduced ROS levels, inhibited JNK activation, and suppressed pyroptosis, supporting its utility as a chemical tool to confirm the pivotal role of ROS/JNK/NLRP3 signaling. This study elucidates the intricate interplay between oxidative stress, mitochondrial dysfunction, and pyroptosis, providing a comprehensive framework for addressing inflammation-driven vascular damage.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"201 ","pages":"Article 115488"},"PeriodicalIF":3.9,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143887023","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}
{"title":"Bioactive molecules in wheat “Senatore Cappelli\" food chain: Extraction, analysis, processing, and beneficial properties","authors":"Federica Armeli , Marzia Beccaccioli , Sabrina Antonia Prencipe , Emily Schifano , Daniela Tufi , Elisa Brasili , Alessia Cottarelli , Ottavia Giampaoli , Beatrice Mengoni , Alfredo Miccheli , Alessandro Pinto , Fabio Sciubba , Daniela Uccelletti , Rita Businaro , Giuliana Vinci , Massimo Reverberi , Maria De Giusti","doi":"10.1016/j.fct.2025.115475","DOIUrl":"10.1016/j.fct.2025.115475","url":null,"abstract":"<div><div>Ancient grains, once forgotten due to the dominance of high-yield modern crops, are making a comeback due to concerns over biodiversity loss and global food challenges. This study examines the nutritional composition, safety, and health benefits of <em>Senatore Cappelli</em>, an ancient Italian durum wheat variety (SCW), highlighting its potential as a functional food. Using a multi-method approach, SCW was analyzed across four food chain stages (seeds, flour, pasta, and chaff) for compositional changes, phytochemical content, and safety. The safety of raw material was assessed by determination of biogenic amines, pesticides, mycotoxins and pathogenic microorganisms. The chemical profile detected by NMR spectroscopy revealed the presence of bioactive molecules such as phenolic acids and carotenoids in the case of chaff. The toxicity of ethanolic extracts was evaluated using <em>in vitro</em> assays on murine BV-2 microglial cells and <em>in vivo</em> assays on <em>Caenorhabditis elegans</em> animal model. No cytotoxic effects were detected at concentrations up to 250 ng/mL for chaff extract and 1000 ng/mL for seed, flour, and pasta extracts. Additionally, SCW extracts extended the lifespan of <em>C. elegans</em>, indicating potential anti-aging and health-promoting properties.</div><div>These results position SCW as a valuable resource for enhancing bioactive compounds, supporting its reintroduction into modern diets and its use in functional food development.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"201 ","pages":"Article 115475"},"PeriodicalIF":3.9,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143887022","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}
A.M. Api , A. Bartlett , D. Belsito , D. Botelho , M. Bruze , A. Bryant-Friedrich , G.A. Burton Jr. , 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 , Y. Thakkar
{"title":"Update to RIFM fragrance ingredient safety assessment, benzyl formate, CAS Registry Number 104-57-4","authors":"A.M. Api , A. Bartlett , D. Belsito , D. Botelho , M. Bruze , A. Bryant-Friedrich , G.A. Burton Jr. , 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 , Y. Thakkar","doi":"10.1016/j.fct.2025.115481","DOIUrl":"10.1016/j.fct.2025.115481","url":null,"abstract":"","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"201 ","pages":"Article 115481"},"PeriodicalIF":3.9,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143886480","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}
A.M. Api , A. Bartlett , D. Belsito , D. Botelho , M. Bruze , A. Bryant-Friedrich , G.A. Burton Jr. , 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 , Y. Thakkar
{"title":"Update to RIFM fragrance ingredient safety assessment, 1,1-diethoxyheptane, CAS Registry Number 688-82-4","authors":"A.M. Api , A. Bartlett , D. Belsito , D. Botelho , M. Bruze , A. Bryant-Friedrich , G.A. Burton Jr. , 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 , Y. Thakkar","doi":"10.1016/j.fct.2025.115470","DOIUrl":"10.1016/j.fct.2025.115470","url":null,"abstract":"<div><div>1,1-Diethoxyheptane was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, photoirritation/photoallergenicity, skin sensitization, and environmental safety. Data from read-across analog octanal dimethyl acetal (CAS # 10022-28-3) show that 1,1-diethoxyheptane is not expected to be genotoxic. The repeated dose, reproductive, and local respiratory toxicity endpoints were evaluated using the Threshold of Toxicological Concern (TTC) for a Cramer Class I material, and the exposure to 1,1-diethoxyheptane is below the TTC (0.03 mg/kg/day, 0.03 mg/kg/day, and 1.4 mg/day, respectively). The skin sensitization endpoint was completed using the Dermal Sensitization Threshold (DST) for non-reactive materials (900 μg/cm<sup>2</sup>); exposure is below the DST. The photoirritation/photoallergenicity endpoints were evaluated based on ultraviolet/visible (UV/Vis) spectra; 1,1-diethoxyheptane is not expected to be photoirritating/photoallergenic. The environmental endpoints were evaluated; 1,1-diethoxyheptane was found not to be Persistent, Bioaccumulative, and Toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards, and its risk quotients, based on its current volume of use (VoU) in Europe and North America (i.e., Predicted Environmental Concentration/Predicted No Effect Concentration [PEC/PNEC]), are <1.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"201 ","pages":"Article 115470"},"PeriodicalIF":3.9,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143891671","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}
Miao Yang , Jialin Sun , Xin Cao , Hongjuan Liu , Xudong Wu , Weifeng Mao , Liping Hao
{"title":"Comparative toxicity analysis of benzo[a]pyrene and PAH4 on HepG2 cells using transcriptomics and metabolomics","authors":"Miao Yang , Jialin Sun , Xin Cao , Hongjuan Liu , Xudong Wu , Weifeng Mao , Liping Hao","doi":"10.1016/j.fct.2025.115473","DOIUrl":"10.1016/j.fct.2025.115473","url":null,"abstract":"<div><div>Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants posing potential health risks. PAH4 (sum of benzo[a]pyrene (BaP), chrysene, benz[a]anthracene and benzo[b]fluoranthene) has been proposed as a marker to evaluate the occurrence of total PAHs. However, toxicity effects of exposure to PAH4 mixture and its toxicity differences with single PAH are little-known. Here, we systematically investigated the hepatotoxicity mechanisms of PAH4 and compare its toxicity with BaP using HepG2 cell model. Our results showed that BaP and PAH4 exposure induced cytotoxicity and oxidative stress. Furthermore, both BaP and PAH4 activated P53 signaling pathway, leading to cell apoptosis, and disrupted peroxisome proliferator-activated receptor (PPAR) signaling and induced lipid metabolism disorder. Integrated analysis of transcriptomics and metabolomics indicated that BaP and PAH4 shared similar toxicity mechanisms, commonly affecting the metabolic pathways including glycerolipid and glycerophospholipid metabolism. Moreover, the integrated biomarker response (IBR) analysis demonstrated that BaP and PAH4 exhibited similar global toxicity on HepG2 cells. We further found that the toxicity effects of PAH4 could be partially alleviated by an aryl hydrocarbon receptor (AHR) antagonist, indicating a potential role of AHR signaling in PAH4-induced hepatotoxicity. Overall, these findings provided insights into the toxicological mechanisms and interaction effects of PAHs mixtures.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"201 ","pages":"Article 115473"},"PeriodicalIF":3.9,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143879299","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}
Menekşe Ülger, Işıl Tuğçe Turan, Ayşegül Si̇pahi̇, Gözde Özge Önder
{"title":"Experimental evaluation of favipiravir (T-705)-induced liver and kidney toxicity in rats","authors":"Menekşe Ülger, Işıl Tuğçe Turan, Ayşegül Si̇pahi̇, Gözde Özge Önder","doi":"10.1016/j.fct.2025.115472","DOIUrl":"10.1016/j.fct.2025.115472","url":null,"abstract":"<div><div>Favipiravir is an antiviral drug that selectively and potently inhibits RNA-dependent RNA polymerase of various RNA viruses. Its empirical use has increased with the COVID-19 pandemic. This study aimed to investigate the potential toxicological effects of favipiravir administration on healthy rats' liver and kidney tissues. Four groups were established in the survey (n = 10): Control, Low-dose favipiravir (100 mg/kg/d), Medium-dose favipiravir (200 mg/kg/d), and High-dose favipiravir (300 mg/kg/d). On the first day of the study, a loading dose equivalent to twice the maintenance dose was administered. On the eleventh day, liver and kidney tissues were collected for histopathological and immunohistochemical analyses. According to our results, favipiravir caused various histopathological damages in the liver and kidneys and led to alterations in the levels of cytokines associated with inflammation (IL-6, TGF-β, TNF-α, IL-1β, IFN-γ). Co-administration of favipiravir with various protective agents may be needed to mitigate potential damage to the liver and kidneys.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"202 ","pages":"Article 115472"},"PeriodicalIF":3.9,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143887113","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}
Ziyu Kong , Lu Zhu , Yi Liu , Yi Liu , Guanghui Chen , Hui Wang
{"title":"Effects of different stages, dosages and courses of prenatal dexamethasone exposure on testicular development in mice","authors":"Ziyu Kong , Lu Zhu , Yi Liu , Yi Liu , Guanghui Chen , Hui Wang","doi":"10.1016/j.fct.2025.115468","DOIUrl":"10.1016/j.fct.2025.115468","url":null,"abstract":"<div><h3>Purpose</h3><div>Observe the effects of prenatal dexamethasone exposure (PDE) at different stages, dosages, and courses on testicular morphology and multicellular function in offspring mice.</div></div><div><h3>Methods</h3><div>Pregnant Kunming mice were subjected to subcutaneous injections of dexamethasone at different stages [GD (gestational day) 14–15 and 16–17], dosages (0.2, 0.4, and 0.8 mg/kg·d), and courses (GD 14–15 and 14–17). Pregnant mice were euthanized on GD 18, and fetal serum and testicular samples were collected to assess serum testosterone level, testicular morphology, cellular proliferation/apoptosis function, expression of multicellular marker/functional gene, and the expression of developmental regulatory signalling pathways such as Notch and Wnt.</div></div><div><h3>Results</h3><div>PDE could lead to widening of the interstitial area and reduction of seminiferous tubules in fetal testicular tissue, accompanied by significant impairment of Sertoli cell function, particularly evident during late gestation, at high doses, and with multiple courses. However, changes in Leydig cells and spermatogonia function of PDE are not significant. Furthermore, we discovered that PDE could activate the Notch signalling pathway in Sertoli cells while inhibiting the Wnt signalling pathway.</div></div><div><h3>Conclusion</h3><div>PDE could affect fetal testicular development, especially for Sertoli cells during late gestation, at high doses and multiple courses. This study confirms the effects of PDE on testicular tissue morphology and multicellular function, providing a comprehensive understanding of the testicular developmental toxicity of dexamethasone and evidence for guiding rational medication during pregnancy.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"201 ","pages":"Article 115468"},"PeriodicalIF":3.9,"publicationDate":"2025-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143873960","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}
{"title":"Gene expression profiles related to apoptosis and levels of DNA oxidative damage in primary dermal fibroblast cells (ATCC® PCS-201-012TM) treated with zirconium oxide nanoparticles","authors":"Gizem Barut , Ayla Çelik","doi":"10.1016/j.fct.2025.115446","DOIUrl":"10.1016/j.fct.2025.115446","url":null,"abstract":"<div><div>Nanoparticles have attracted growing interest in recent years. They are small and can easily penetrate into cells. We investigated the genotoxic, cytotoxic, and apoptotic effects of zirconium nanoparticles on dermal fibroblast cells, the comet assay, Xcelligence system, and apoptotic gene expression, respectively. The comet assay analysis showed a non-signifcant increase in the genetic damage index and the percentage of damaged cells in the groups exposed to 10 and 20-nm zirconium oxide nanoparticles. Xcelligence system analysis observed a decrease in the indices of cells exposed to 10 and 20 nm zirconium oxide nanoparticles in the 48th-hour, 72nd-hour, and 96th-hour data. It was observed that caspase 3 and caspase 8 gene expression levels were suppressed in cells exposed to 10 and 20 nm zirconium oxide nanoparticles. Compared to the negative control group, this suppression was significant in the 10 nm groups (p < 0.01) while it was not significant in the 20 nm groups. Although zirconium oxide nanoparticles do not show toxicity and genotoxicity at a given concentration, but the overall mechanism is still not clear regarding the consequences of these nanoparticles use and its efect on living system. However, our apoptotic gene expression studies concluded that the nanoparticle size, particularly 10 nm, had an impact on gene expression.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"201 ","pages":"Article 115446"},"PeriodicalIF":3.9,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143873959","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}
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 , Y. Thakkar
{"title":"Update to RIFM fragrance ingredient safety assessment, amyl hexanoate, CAS registry number 540-07-8","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 , Y. Thakkar","doi":"10.1016/j.fct.2025.115463","DOIUrl":"10.1016/j.fct.2025.115463","url":null,"abstract":"","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"201 ","pages":"Article 115463"},"PeriodicalIF":3.9,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143867744","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}