Pub Date : 2026-05-01Epub Date: 2026-02-05DOI: 10.1016/j.fct.2026.115988
Rong-Yue Xue, Hong-Bo Li
{"title":"Response to the Letter to the Editor: “Translational perspectives on dietary prebiotics and iron for reducing rice cadmium bioavailability\"","authors":"Rong-Yue Xue, Hong-Bo Li","doi":"10.1016/j.fct.2026.115988","DOIUrl":"10.1016/j.fct.2026.115988","url":null,"abstract":"","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"211 ","pages":"Article 115988"},"PeriodicalIF":3.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146130604","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}
Pub Date : 2026-05-01Epub Date: 2026-02-10DOI: 10.1016/j.fct.2026.115989
Gizem Zorlu Gorgulugil, Muhammed Ali Coskuner, Gokhan Koker
{"title":"Translational perspectives on dietary prebiotics and iron for reducing rice cadmium bioavailability","authors":"Gizem Zorlu Gorgulugil, Muhammed Ali Coskuner, Gokhan Koker","doi":"10.1016/j.fct.2026.115989","DOIUrl":"10.1016/j.fct.2026.115989","url":null,"abstract":"","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"211 ","pages":"Article 115989"},"PeriodicalIF":3.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146176817","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}
The toxicity of arsenic has been well established for millennia, with epidemiological data demonstrating the association of inorganic arsenic (iAs) to cancers and dermal defects. Recently, epidemiological and mechanistic studies linking dietary iAs exposure to cardiovascular diseases (CVD) have emerged. Despite growing evidence on iAs induced CVD, current toxicological reference values (TRVs) for dietary iAs are largely based on cancer, peripheral vascular (“blackfoot”) disease, diabetes and dermal endpoints. To bridge this gap, the current study estimated TRVs for food borne iAs using the benchmark dose (BMD) approach, by modeling dose-response data of multiple CVD endpoints identified from literature. The estimated TRVs for CVD incidence were in the range of 0.027-0.037 μg/kg bw/day and were lower than TRVs estimated by regulatory bodies. TRVs estimated based on CVD mortality alone were in the range of 0.074-0.729 μg/kg bw/day. A TRV of 0.03 μg/kg bw/day based on coronary heart disease incidence was considered appropriate from a regulatory standpoint. The TRV estimate suggests that iAs induced cardiovascular diseases are an important endpoint from a policymaking perspective on maximum allowable arsenic levels in food.
{"title":"Deriving toxicological reference values for dietary inorganic arsenic exposure from epidemiological evidence of cardiovascular disease risk","authors":"Charitha J. Gamlath , Patricia Hsu , Ashish Pokharel , Felicia Wu","doi":"10.1016/j.fct.2026.116008","DOIUrl":"10.1016/j.fct.2026.116008","url":null,"abstract":"<div><div>The toxicity of arsenic has been well established for millennia, with epidemiological data demonstrating the association of inorganic arsenic (iAs) to cancers and dermal defects. Recently, epidemiological and mechanistic studies linking dietary iAs exposure to cardiovascular diseases (CVD) have emerged. Despite growing evidence on iAs induced CVD, current toxicological reference values (TRVs) for dietary iAs are largely based on cancer, peripheral vascular (“blackfoot”) disease, diabetes and dermal endpoints. To bridge this gap, the current study estimated TRVs for food borne iAs using the benchmark dose (BMD) approach, by modeling dose-response data of multiple CVD endpoints identified from literature. The estimated TRVs for CVD incidence were in the range of 0.027-0.037 μg/kg bw/day and were lower than TRVs estimated by regulatory bodies. TRVs estimated based on CVD mortality alone were in the range of 0.074-0.729 μg/kg bw/day. A TRV of 0.03 μg/kg bw/day based on coronary heart disease incidence was considered appropriate from a regulatory standpoint. The TRV estimate suggests that iAs induced cardiovascular diseases are an important endpoint from a policymaking perspective on maximum allowable arsenic levels in food.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"211 ","pages":"Article 116008"},"PeriodicalIF":3.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146176861","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}
Perfluorohexanesulfonic acid (PFHxS), a prevalent short-chain per- and polyfluoroalkyl substance, has been implicated in hepatocellular carcinoma (HCC), but mechanisms remain unclear. We integrated transcriptomic analyses of The Cancer Genome Atlas (TCGA) liver cancer cohort and an HCC single-cell dataset with molecular docking and molecular dynamics simulations and in vitro assays to examine a PFHxS-relevant hypothesis involving KEAP1–NRF2 signaling. Across clinical datasets, higher NQO1, an NRF2-associated gene, was linked to adverse clinicopathologic features; NQO1-high tumor cells showed elevated NRF2-activity signatures and computationally inferred increased MIF signaling toward macrophages. Because exposure information is unavailable, these observations indicate association and define a PFHxS-relevant vulnerability axis rather than PFHxS-driven tumor states. Docking/dynamics suggested PFHxS can bind the KEAP1 Kelch domain near the NRF2-binding site. In HepG2 cells, PFHxS modestly increased viability/DNA-synthesis readouts and enhanced NRF2 nuclear localization, NQO1 protein abundance, and MIF secretion; pharmacologic NRF2 inhibition partially attenuated NRF2/NQO1 readouts and reduced MIF secretion. Together, the data support the hypothesis that PFHxS may engage a KEAP1–NRF2-related vulnerability axis, accompanied by NRF2/NQO1 pathway readouts and increased MIF secretion, motivating exposure-characterized and genetic studies to establish causality.
{"title":"PFHxS is predicted to bind KEAP1 and is associated with NRF2–NQO1 activation in hepatocellular carcinoma","authors":"Chenghao He , Jiaxin Jiang , Shuguang Hou , Runchun Xu , Qinwan Huang","doi":"10.1016/j.fct.2026.115986","DOIUrl":"10.1016/j.fct.2026.115986","url":null,"abstract":"<div><div>Perfluorohexanesulfonic acid (PFHxS), a prevalent short-chain per- and polyfluoroalkyl substance, has been implicated in hepatocellular carcinoma (HCC), but mechanisms remain unclear. We integrated transcriptomic analyses of The Cancer Genome Atlas (TCGA) liver cancer cohort and an HCC single-cell dataset with molecular docking and molecular dynamics simulations and in vitro assays to examine a PFHxS-relevant hypothesis involving KEAP1–NRF2 signaling. Across clinical datasets, higher NQO1, an NRF2-associated gene, was linked to adverse clinicopathologic features; NQO1-high tumor cells showed elevated NRF2-activity signatures and computationally inferred increased MIF signaling toward macrophages. Because exposure information is unavailable, these observations indicate association and define a PFHxS-relevant vulnerability axis rather than PFHxS-driven tumor states. Docking/dynamics suggested PFHxS can bind the KEAP1 Kelch domain near the NRF2-binding site. In HepG2 cells, PFHxS modestly increased viability/DNA-synthesis readouts and enhanced NRF2 nuclear localization, NQO1 protein abundance, and MIF secretion; pharmacologic NRF2 inhibition partially attenuated NRF2/NQO1 readouts and reduced MIF secretion. Together, the data support the hypothesis that PFHxS may engage a KEAP1–NRF2-related vulnerability axis, accompanied by NRF2/NQO1 pathway readouts and increased MIF secretion, motivating exposure-characterized and genetic studies to establish causality.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"211 ","pages":"Article 115986"},"PeriodicalIF":3.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146103338","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}
Pub Date : 2026-05-01Epub Date: 2026-01-29DOI: 10.1016/j.fct.2026.115984
Edward J. Calabrese , Peter Pressman , A. Wallace Hayes , Evgenios Agathokleous , Gaurav Dhawan , Rachna Kapoor , Vittorio Calabrese
This present paper provides the first integrative evaluation of the occurrence of emodin-induced hormetic-biphasic dose responses in the biological and biomedical literature, their study design and dose-response features, underlying adaptive and toxic mechanistic foundations, and generality across biological models, cell types, as well as across different levels of biological organization (i.e., cell, organ, and organism). Emodin-induced hormetic responses have been reported in numerous cellular experimental systems of broad biomedical interest, as well as in in vivo studies with fish and rodent models. Of particular interest was the generality of the in vivo findings across multiple commercial fish models, in which emodin enhanced growth and development and increased resistance to various physical and environmental stressors. While emodin induces hormetic effects via multiple molecular targets and pathways, a general mechanistic adaptive response strategy involves its capacity to activate peroxisome proliferator-activated receptor gamma and the AMPK/Nrf2 pathway.
{"title":"Emodin: Its effects are largely due to hormesis","authors":"Edward J. Calabrese , Peter Pressman , A. Wallace Hayes , Evgenios Agathokleous , Gaurav Dhawan , Rachna Kapoor , Vittorio Calabrese","doi":"10.1016/j.fct.2026.115984","DOIUrl":"10.1016/j.fct.2026.115984","url":null,"abstract":"<div><div>This present paper provides the first integrative evaluation of the occurrence of emodin-induced hormetic-biphasic dose responses in the biological and biomedical literature, their study design and dose-response features, underlying adaptive and toxic mechanistic foundations, and generality across biological models, cell types, as well as across different levels of biological organization (i.e., cell, organ, and organism). Emodin-induced hormetic responses have been reported in numerous cellular experimental systems of broad biomedical interest, as well as in <em>in vivo</em> studies with fish and rodent models. Of particular interest was the generality of the <em>in vivo</em> findings across multiple commercial fish models, in which emodin enhanced growth and development and increased resistance to various physical and environmental stressors. While emodin induces hormetic effects via multiple molecular targets and pathways, a general mechanistic adaptive response strategy involves its capacity to activate peroxisome proliferator-activated receptor gamma and the AMPK/Nrf2 pathway.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"211 ","pages":"Article 115984"},"PeriodicalIF":3.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146096801","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}
Pub Date : 2026-05-01Epub Date: 2026-01-20DOI: 10.1016/j.fct.2026.115969
F. Peter Guengerich , Samuel M. Cohen , Gerhard Eisenbrand , Shoji Fukushima , Nigel J. Gooderham , Stephen S. Hecht , Ivonne M.C.M. Rietjens , Thomas J. Rosol , Jeanne M. Davidsen , Christie L. Harman , Sean V. Taylor
The Expert Panel of the Flavor and Extract Manufacturers Association (FEMA) is conducting a program to re-evaluate the safety of over 250 natural flavor complexes (NFCs) used as flavoring ingredients. This publication, fourteenth in the series, evaluates the safety of NFCs composed primarily of benzaldehyde, methyl salicylate, vanillin and other benzyl derivative compounds. In 2018, the Expert Panel published an update of its safety evaluation procedure for NFCs that was first published in 2005. This procedure relies on a complete constituent characterization of the NFC and organization of the constituents of each NFC into defined congeneric groups. The safety of the NFC is evaluated using the threshold of toxicological concern (TTC) approach using updated estimates of exposure in addition to the evaluation of all relevant safety data on the NFC and its principal constituents. The scope of the safety evaluation contained herein does not include added use in dietary supplements or any products other than food. Eighteen (18) NFCs, derived from the Vanilla, Prunus, Betula, Acacia, Cuminum, Jasminum, Gaultheria, Polianthes and Evernia genera, were affirmed as generally recognized as safe (GRAS) under their conditions of intended use as flavor ingredients, based on an evaluation of each NFC and the constituents and congeneric groups therein.
{"title":"FEMA GRAS assessment of natural flavor complexes: Vanilla extract, Bitter almond oil, Wintergreen oil and related flavoring ingredients","authors":"F. Peter Guengerich , Samuel M. Cohen , Gerhard Eisenbrand , Shoji Fukushima , Nigel J. Gooderham , Stephen S. Hecht , Ivonne M.C.M. Rietjens , Thomas J. Rosol , Jeanne M. Davidsen , Christie L. Harman , Sean V. Taylor","doi":"10.1016/j.fct.2026.115969","DOIUrl":"10.1016/j.fct.2026.115969","url":null,"abstract":"<div><div>The Expert Panel of the Flavor and Extract Manufacturers Association (FEMA) is conducting a program to re-evaluate the safety of over 250 natural flavor complexes (NFCs) used as flavoring ingredients. This publication, fourteenth in the series, evaluates the safety of NFCs composed primarily of benzaldehyde, methyl salicylate, vanillin and other benzyl derivative compounds. In 2018, the Expert Panel published an update of its safety evaluation procedure for NFCs that was first published in 2005. This procedure relies on a complete constituent characterization of the NFC and organization of the constituents of each NFC into defined congeneric groups. The safety of the NFC is evaluated using the threshold of toxicological concern (TTC) approach using updated estimates of exposure in addition to the evaluation of all relevant safety data on the NFC and its principal constituents. The scope of the safety evaluation contained herein does not include added use in dietary supplements or any products other than food. Eighteen (18) NFCs, derived from the <em>Vanilla</em>, <em>Prunus, Betula, Acacia, Cuminum, Jasminum, Gaultheria, Polianthes and Evernia</em> genera, were affirmed as generally recognized as safe (GRAS) under their conditions of intended use as flavor ingredients, based on an evaluation of each NFC and the constituents and congeneric groups therein.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"211 ","pages":"Article 115969"},"PeriodicalIF":3.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146027922","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}
Pub Date : 2026-05-01Epub Date: 2026-02-05DOI: 10.1016/j.fct.2026.115991
Siyan Cao , Runzhi Cai , Shuhua Xi , Yue Wang
Arsenic is a prevalent environmental contaminant found in contaminated drinking water. However, the effects of arsenic exposure on the intestinal tract and the specific mechanisms of action remain unclear. In this study, we utilized subchronic sodium arsenite (NaAsO2)-exposed mice and the NaAsO2-treated human colon mucosal epithelial cell line 460 (NCM460) models to investigate the intestinal damage induced by arsenic. Hematoxylin-eosin (HE) staining revealed that the intestines of mice exposed to arsenic exhibited histological damage, characterized by the destruction of epithelial cells, a reduction in the thickness of the muscularis propria, and an increased infiltration of inflammatory cells within the colonic tissue. Mice exposed to arsenic demonstrated a significant reduction in the expression levels of the Occludin protein, accompanied by elevated concentrations of two biomarkers indicative of intestinal barrier damage: serum diamine oxidase (DAO) and lactate (D-LA). Analysis using 16S rRNA sequencing revealed that arsenic exposure did not significantly affect the α and β diversity of the mouse gut microbiota. However, it resulted in changes in the abundance of Clostridiaceae, Burkholderiaceae, Erysipelotrichaceae, and Helicobacteraceae increased, while Muribaculaceae decreased. Furthermore, exposure to arsenic led to increased protein levels of IL-1β, IL-6, and TNF-α, while simultaneously decreasing the expression of IL-10. Arsenic activated NF-κB signaling pathway, which involved in colonic inflammation. Finally, intervention with Pyrrolidine dithiocarbamate (PDTC) significantly attenuated arsenic-induced intestinal inflammation. In conclusion, arsenic exposure compromises the integrity of the intestinal mucosa and disrupts the homeostasis of the intestinal microbiota. Additionally, arsenic mediates intestinal inflammation through the NF-κB signaling pathway.
{"title":"Subchronic arsenic exposure induced intestinal microbiota dysbiosis and intestinal inflammation via activating the NF-κB signaling pathway","authors":"Siyan Cao , Runzhi Cai , Shuhua Xi , Yue Wang","doi":"10.1016/j.fct.2026.115991","DOIUrl":"10.1016/j.fct.2026.115991","url":null,"abstract":"<div><div>Arsenic is a prevalent environmental contaminant found in contaminated drinking water. However, the effects of arsenic exposure on the intestinal tract and the specific mechanisms of action remain unclear. In this study, we utilized subchronic sodium arsenite (NaAsO2)-exposed mice and the NaAsO2-treated human colon mucosal epithelial cell line 460 (NCM460) models to investigate the intestinal damage induced by arsenic. Hematoxylin-eosin (HE) staining revealed that the intestines of mice exposed to arsenic exhibited histological damage, characterized by the destruction of epithelial cells, a reduction in the thickness of the muscularis propria, and an increased infiltration of inflammatory cells within the colonic tissue. Mice exposed to arsenic demonstrated a significant reduction in the expression levels of the Occludin protein, accompanied by elevated concentrations of two biomarkers indicative of intestinal barrier damage: serum diamine oxidase (DAO) and lactate (D-LA). Analysis using 16S rRNA sequencing revealed that arsenic exposure did not significantly affect the α and β diversity of the mouse gut microbiota. However, it resulted in changes in the abundance of Clostridiaceae, Burkholderiaceae, Erysipelotrichaceae, and Helicobacteraceae increased, while Muribaculaceae decreased. Furthermore, exposure to arsenic led to increased protein levels of IL-1β, IL-6, and TNF-α, while simultaneously decreasing the expression of IL-10. Arsenic activated NF-κB signaling pathway, which involved in colonic inflammation. Finally, intervention with Pyrrolidine dithiocarbamate (PDTC) significantly attenuated arsenic-induced intestinal inflammation. In conclusion, arsenic exposure compromises the integrity of the intestinal mucosa and disrupts the homeostasis of the intestinal microbiota. Additionally, arsenic mediates intestinal inflammation through the NF-κB signaling pathway.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"211 ","pages":"Article 115991"},"PeriodicalIF":3.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146136971","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}
Pub Date : 2026-05-01Epub Date: 2026-01-29DOI: 10.1016/j.fct.2026.115985
Daniel Blascke Carrão , Isabel Cristina dos Reis Gomes , Fernando Barbosa Junior , Anderson Rodrigo Moraes de Oliveira
{"title":"Corrigendum to “Evaluation of the enantioselective in vitro metabolism of the chiral pesticide fipronil employing a human model: Risk assessment through in vitro-in vivo correlation and prediction of toxicokinetic parameters” [Food Chem. Toxicol. 123 (2019) 225–232]","authors":"Daniel Blascke Carrão , Isabel Cristina dos Reis Gomes , Fernando Barbosa Junior , Anderson Rodrigo Moraes de Oliveira","doi":"10.1016/j.fct.2026.115985","DOIUrl":"10.1016/j.fct.2026.115985","url":null,"abstract":"","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"211 ","pages":"Article 115985"},"PeriodicalIF":3.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146071011","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}
Pub Date : 2026-05-01Epub Date: 2026-02-07DOI: 10.1016/j.fct.2026.116004
Yufeng Ma , Xinyue Mai , Wenxi Fan , Xue Sun , Yongsen He , Jielu Zhang , Tianbao Wang , Yi Zuo , Tingting Zhang , Jun Lu
Benzoic acid (BA) and acesulfame K (ACE) are commonly co-present food additives, yet their combined nephrotoxic risk remains poorly understood. Employing network toxicology, molecular simulations, and in vitro assays, we systematically evaluated their individual and combined effects on nephrotoxicity. Computational predictions indicated that both compounds exhibited nephrotoxic propensity, with shared targets enriched in pathways such as “response to xenobiotic stimulus” and metabolic disruption. Protein–protein interaction network analysis identified CTNNB1 and STAT3 as the respective core targets for BA and ACE, with molecular simulations confirming their stable binding. In vitro experiments showed that BA alone inhibited HK2 cell proliferation, and downregulated β-catenin (encoded by CTNNB1). ACE alone did not significantly suppress proliferation but activated STAT3 signaling. Notably, combined exposure produced a marked synergistic anti-proliferative effect, attributable to a dual mechanism: BA impaired renal tubular repair capacity by suppressing the CTNNB1/β-catenin pathway, while ACE exacerbated inflammatory and injury responses via STAT3 activation, thereby simultaneously impairing repair and exacerbating damage in the kidney. This study is the first to reveal that BA and ACE have the potential to synergistically induce nephrotoxicity via the CTNNB1/STAT3 signaling axis, providing new scientific evidence for the systematic safety assessment of mixed food-additive exposures.
{"title":"Co-exposure to benzoic acid and acesulfame K synergistically induces nephrotoxicity through the CTNNB1/STAT3 axis","authors":"Yufeng Ma , Xinyue Mai , Wenxi Fan , Xue Sun , Yongsen He , Jielu Zhang , Tianbao Wang , Yi Zuo , Tingting Zhang , Jun Lu","doi":"10.1016/j.fct.2026.116004","DOIUrl":"10.1016/j.fct.2026.116004","url":null,"abstract":"<div><div>Benzoic acid (BA) and acesulfame K (ACE) are commonly co-present food additives, yet their combined nephrotoxic risk remains poorly understood. Employing network toxicology, molecular simulations, and <em>in vitro</em> assays, we systematically evaluated their individual and combined effects on nephrotoxicity. Computational predictions indicated that both compounds exhibited nephrotoxic propensity, with shared targets enriched in pathways such as “response to xenobiotic stimulus” and metabolic disruption. Protein–protein interaction network analysis identified CTNNB1 and STAT3 as the respective core targets for BA and ACE, with molecular simulations confirming their stable binding. <em>In vitro</em> experiments showed that BA alone inhibited HK2 cell proliferation, and downregulated β-catenin (encoded by CTNNB1). ACE alone did not significantly suppress proliferation but activated STAT3 signaling. Notably, combined exposure produced a marked synergistic anti-proliferative effect, attributable to a dual mechanism: BA impaired renal tubular repair capacity by suppressing the CTNNB1/β-catenin pathway, while ACE exacerbated inflammatory and injury responses via STAT3 activation, thereby simultaneously impairing repair and exacerbating damage in the kidney. This study is the first to reveal that BA and ACE have the potential to synergistically induce nephrotoxicity via the CTNNB1/STAT3 signaling axis, providing new scientific evidence for the systematic safety assessment of mixed food-additive exposures.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"211 ","pages":"Article 116004"},"PeriodicalIF":3.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146140559","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}
Pub Date : 2026-05-01Epub Date: 2026-02-06DOI: 10.1016/j.fct.2026.115982
Silin Kong , Kexin Zhang , Jiajun Sang , Jingwen Zhang , Chengxia Kan , Xiaodong Sun , Ningning Hou
Micro- and nanoplastics (MNPs) and fine particulate matter (PM2.5) have emerged as independent yet underrecognized environmental risk factors for cardiovascular disease (CVD). Their ultrafine size, large surface area, and high adsorptive capacity not only facilitate epithelial penetration and systemic translocation but also enable direct interactions with vascular and cardiac tissues. Growing epidemiological and experimental evidence links chronic exposure to MNPs and PM2.5 with endothelial dysfunction, atherogenesis, arrhythmogenesis, and myocardial injury. To ensure comprehensive coverage, we systematically searched PubMed, Web of Science, Embase, and Scopus for studies that investigated cardiovascular or metabolic effects of MNP and PM2.5 exposure. We synthesized available epidemiological and mechanistic evidence, focusing on the central role of oxidative stress, mitochondrial dysfunction, ferroptosis, immunometabolic reprogramming, endocrine disruption, and epigenetic remodeling in pollutant-induced cardiovascular pathology. These interrelated processes collectively impair endothelial function, promote atherosclerosis, and compromise cardiac integrity. This narrative review integrates emerging mechanistic insights, identifies potential early diagnostic biomarkers and therapeutic targets, and discusses prevention and policy strategies.
微和纳米塑料（MNPs）和细颗粒物（PM2.5）已成为心血管疾病（CVD）的独立但未得到充分认识的环境危险因素。它们的超细尺寸、大表面积和高吸附能力不仅有利于上皮细胞的渗透和全身移位，而且能够与血管和心脏组织直接相互作用。越来越多的流行病学和实验证据表明，长期暴露于MNPs和PM2.5与内皮功能障碍、动脉粥样硬化、心律失常和心肌损伤有关。为了确保全面覆盖，我们系统地检索了PubMed、Web of Science、Embase和Scopus，以调查MNP和PM2.5暴露对心血管或代谢的影响。我们综合了现有的流行病学和机制证据，重点关注氧化应激、线粒体功能障碍、铁下沉、免疫代谢重编程、内分泌干扰和表观遗传重塑在污染物诱导的心血管病理中的核心作用。这些相互关联的过程共同损害内皮功能，促进动脉粥样硬化，损害心脏完整性。这篇叙述性综述整合了新兴的机制见解，确定了潜在的早期诊断生物标志物和治疗靶点，并讨论了预防和政策策略。
{"title":"Micro- and nanoplastics and PM2.5 in cardiovascular disease: Emerging mechanisms, impacts, and therapeutic insights","authors":"Silin Kong , Kexin Zhang , Jiajun Sang , Jingwen Zhang , Chengxia Kan , Xiaodong Sun , Ningning Hou","doi":"10.1016/j.fct.2026.115982","DOIUrl":"10.1016/j.fct.2026.115982","url":null,"abstract":"<div><div>Micro- and nanoplastics (MNPs) and fine particulate matter (PM2.5) have emerged as independent yet underrecognized environmental risk factors for cardiovascular disease (CVD). Their ultrafine size, large surface area, and high adsorptive capacity not only facilitate epithelial penetration and systemic translocation but also enable direct interactions with vascular and cardiac tissues. Growing epidemiological and experimental evidence links chronic exposure to MNPs and PM2.5 with endothelial dysfunction, atherogenesis, arrhythmogenesis, and myocardial injury. To ensure comprehensive coverage, we systematically searched PubMed, Web of Science, Embase, and Scopus for studies that investigated cardiovascular or metabolic effects of MNP and PM2.5 exposure. We synthesized available epidemiological and mechanistic evidence, focusing on the central role of oxidative stress, mitochondrial dysfunction, ferroptosis, immunometabolic reprogramming, endocrine disruption, and epigenetic remodeling in pollutant-induced cardiovascular pathology. These interrelated processes collectively impair endothelial function, promote atherosclerosis, and compromise cardiac integrity. This narrative review integrates emerging mechanistic insights, identifies potential early diagnostic biomarkers and therapeutic targets, and discusses prevention and policy strategies.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"211 ","pages":"Article 115982"},"PeriodicalIF":3.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146140514","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号