Pub Date : 2025-12-11DOI: 10.1016/j.fct.2025.115900
Ting Shao, Yue-Lei Chen
Immortalized cell lines function as invaluable tools in life science and preclinical studies. Poor laboratory practices can lead to cell line misidentification, cross-contamination, and mislabelling, resulting in invalid, misleading, and unrepeatable results. The issue of nonhuman-derived cell misidentification was once discovered timely, but it received less attention than the misidentification of human cells. Consequently, problematic murine cell lines still appear frequently in the literature. For instance, ImKC cells have been applied as a mouse Kupffer cell line in the last decade. In this report, we revealed that the ImKC cell line was a RAW 264.7 derivative through STR analysis, and further determined that it was not an SV40-transformed cell line by PCR and western blotting assays. Moreover, we outlined the relevant publications using the ImKC cell line. This study aims to prevent further researchers from employing the problematic cell line in their studies.
{"title":"Multiple approaches revealed ImKC cells as a RAW 264.7 derivative rather than a Kupffer cell line","authors":"Ting Shao, Yue-Lei Chen","doi":"10.1016/j.fct.2025.115900","DOIUrl":"10.1016/j.fct.2025.115900","url":null,"abstract":"<div><div>Immortalized cell lines function as invaluable tools in life science and preclinical studies. Poor laboratory practices can lead to cell line misidentification, cross-contamination, and mislabelling, resulting in invalid, misleading, and unrepeatable results. The issue of nonhuman-derived cell misidentification was once discovered timely, but it received less attention than the misidentification of human cells. Consequently, problematic murine cell lines still appear frequently in the literature. For instance, ImKC cells have been applied as a mouse Kupffer cell line in the last decade. In this report, we revealed that the ImKC cell line was a RAW 264.7 derivative through STR analysis, and further determined that it was not an SV40-transformed cell line by PCR and western blotting assays. Moreover, we outlined the relevant publications using the ImKC cell line. This study aims to prevent further researchers from employing the problematic cell line in their studies.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"209 ","pages":"Article 115900"},"PeriodicalIF":3.5,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145751465","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 : 2025-12-09DOI: 10.1016/j.fct.2025.115892
Hui Jiang , Junhua Yang , Xichun Wang , Lihui Zhu
Deoxynivalenol (DON) and copper (Cu) are crucial food-related contaminants associated with health risks in both animals and humans. This study investigated the individual and combined effects of DON and Cu on a mouse hepatocyte line NCTC1469 cells. The results demonstrated that both DON and Cu induced ultrastructural damage, promoted mitochondrial vacuolization, increased pro-inflammatory cytokine levels, such as interleukin-1β (IL-1β) and tumor necrosis factor-alpha, reduced cell viability, and suppressed antioxidant enzyme activity, including glutathione and superoxide dismutase. Notably, DON + Cu enhanced cell viability compared to DON alone. In addition, co-treatment significantly reduced IL-1β levels relative to DON alone at 0.625, 1.25, and 2.5 μM. Transcriptome sequencing revealed that both DON alone and DON-Cu co-exposure triggered numerous differentially expressed genes, which were notably enriched in autophagy related pathways, such as ribosome biogenesis in eukaryotes, lysosome, spliceosome, and cell cycle. Meanwhile, the relative protein ratio of LC3-II/LC3-I was elevated at 0.65 μM DON, while the p62 expression was decreased in a dose-dependent manner compared to the control. In summary, DON exerts toxic effects on mouse hepatocytes, while Cu can mitigate DON-induced cellular damage at low concentrations, likely through involvement in Beclin-1/p62 related autophagic regulation.
{"title":"Interaction of deoxynivalenol and copper: Cellular and molecular insights in mouse liver cells","authors":"Hui Jiang , Junhua Yang , Xichun Wang , Lihui Zhu","doi":"10.1016/j.fct.2025.115892","DOIUrl":"10.1016/j.fct.2025.115892","url":null,"abstract":"<div><div>Deoxynivalenol (DON) and copper (Cu) are crucial food-related contaminants associated with health risks in both animals and humans. This study investigated the individual and combined effects of DON and Cu on a mouse hepatocyte line NCTC1469 cells. The results demonstrated that both DON and Cu induced ultrastructural damage, promoted mitochondrial vacuolization, increased pro-inflammatory cytokine levels, such as interleukin-1β (IL-1β) and tumor necrosis factor-alpha, reduced cell viability, and suppressed antioxidant enzyme activity, including glutathione and superoxide dismutase. Notably, DON + Cu enhanced cell viability compared to DON alone. In addition, co-treatment significantly reduced IL-1β levels relative to DON alone at 0.625, 1.25, and 2.5 μM. Transcriptome sequencing revealed that both DON alone and DON-Cu co-exposure triggered numerous differentially expressed genes, which were notably enriched in autophagy related pathways, such as ribosome biogenesis in eukaryotes, lysosome, spliceosome, and cell cycle. Meanwhile, the relative protein ratio of LC3-II/LC3-I was elevated at 0.65 μM DON, while the p62 expression was decreased in a dose-dependent manner compared to the control. In summary, DON exerts toxic effects on mouse hepatocytes, while Cu can mitigate DON-induced cellular damage at low concentrations, likely through involvement in Beclin-1/p62 related autophagic regulation.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"208 ","pages":"Article 115892"},"PeriodicalIF":3.5,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145740296","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 doxorubicin and trastuzumab can lead to heart failure. Its pathophysiology is correlated with cardiac metabolic reprogramming. Therefore, we investigated the effects of doxorubicin and trastuzumab on cardiac metabolic reprogramming. Since mitochondrial dynamics imbalance is associated with cardiotoxicity, we evaluated the effects of restoring balance of mitochondrial dynamics on reducing cardiotoxicity. Male Wistar rats received either vehicle, 6 doses of 3 mg/kg of doxorubicin, or 4 mg/kg/day of trastuzumab. Doxorubicin-treated rats and trastuzumab-treated rats were also co-treated with either vehicle, 1.2 mg/kg/day of MDiVi1 (mitochondrial fission inhibitor), or 2 mg/kg/day of M1 (mitochondrial fusion promoter). The treatment duration was 30 and 7 days for doxorubicin and trastuzumab studies, respectively. Thereafter, cardiac function was determined. The rats were then euthanized to collect cardiac ventricular tissues for targeted metabolomics via liquid chromatography coupled with mass spectrometry. We found that doxorubicin and trastuzumab caused increased glycolysis, increased ketone body metabolism, decreased fatty acid utilization, decreased succinate oxidation, and decreased ATP production. These changes were more severe in doxorubicin-treated rats. Restoring mitochondrial dynamics balance by MDiVi1 or M1 improved cardiac metabolic reprogramming. These novel findings highlighted the toxic effects of doxorubicin and trastuzumab on cardiac metabolic reprogramming and their association with mitochondrial dynamics. Also, metabolomics might be used as a tool for treatment monitoring in doxorubicin- and trastuzumab-induced cardiotoxicity.
{"title":"The toxic effects of doxorubicin and trastuzumab on cardiac metabolic reprogramming are associated with impaired mitochondrial dynamics balance","authors":"Chanisa Thonusin , Chayodom Maneechote , Siriporn C. Chattipakorn , Nipon Chattipakorn","doi":"10.1016/j.fct.2025.115895","DOIUrl":"10.1016/j.fct.2025.115895","url":null,"abstract":"<div><div>The toxicity of doxorubicin and trastuzumab can lead to heart failure. Its pathophysiology is correlated with cardiac metabolic reprogramming. Therefore, we investigated the effects of doxorubicin and trastuzumab on cardiac metabolic reprogramming. Since mitochondrial dynamics imbalance is associated with cardiotoxicity, we evaluated the effects of restoring balance of mitochondrial dynamics on reducing cardiotoxicity. Male Wistar rats received either vehicle, 6 doses of 3 mg/kg of doxorubicin, or 4 mg/kg/day of trastuzumab. Doxorubicin-treated rats and trastuzumab-treated rats were also co-treated with either vehicle, 1.2 mg/kg/day of MDiVi1 (mitochondrial fission inhibitor), or 2 mg/kg/day of M1 (mitochondrial fusion promoter). The treatment duration was 30 and 7 days for doxorubicin and trastuzumab studies, respectively. Thereafter, cardiac function was determined. The rats were then euthanized to collect cardiac ventricular tissues for targeted metabolomics via liquid chromatography coupled with mass spectrometry. We found that doxorubicin and trastuzumab caused increased glycolysis, increased ketone body metabolism, decreased fatty acid utilization, decreased succinate oxidation, and decreased ATP production. These changes were more severe in doxorubicin-treated rats. Restoring mitochondrial dynamics balance by MDiVi1 or M1 improved cardiac metabolic reprogramming. These novel findings highlighted the toxic effects of doxorubicin and trastuzumab on cardiac metabolic reprogramming and their association with mitochondrial dynamics. Also, metabolomics might be used as a tool for treatment monitoring in doxorubicin- and trastuzumab-induced cardiotoxicity.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"208 ","pages":"Article 115895"},"PeriodicalIF":3.5,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145740263","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 : 2025-12-09DOI: 10.1016/j.fct.2025.115894
Daniel Silva Sena Bastos , Pedro Henrique de Carvalho Albuquerque de Souza , Mariana Machado-Neves , Luiz Otávio Guimarães-Ervilha , Leandro Licursi de Oliveira , Renê Chagas da Silva , Marcos Antônio José dos Santos , Wallace Martins de Araújo , Ana Cláudia Ferreira Souza
Arsenic is a widespread environmental contaminant capable of crossing the placental barrier, posing risks to fetal development. This study evaluated the long-term effects of prenatal arsenic exposure on the liver and kidney of male Wistar rat offspring at prepubertal (PND15), peripubertal (PND28, 44) and adult (PND70) stages. Pregnant rats received 10 mg/L sodium arsenite in drinking water from gestational day 1 until parturition. Results revealed that prenatal arsenic exposure led to growth restriction until peripuberty and persistent arsenic accumulation in both organs. In the liver, significant alterations included increased serum AST and ALP, and disrupted SOD and CAT activity at different ages. These alterations were accompanied by elevated protein carbonylation and histopathological changes such as inflammation, vascular congestion and hydropic degeneration, especially at peripubertal and adult stages. In contrast, the kidney exhibited enhanced SOD and GST activity without corresponding increases in oxidative damage markers or histopathological lesions, despite some micromineral imbalances. Overall, the liver emerged as the primary target of prenatal arsenic-induced toxicity, whereas the kidney showed increased antioxidant enzyme activity in the absence of overt damage. These findings highlight the importance of intrauterine exposure timing in determining postnatal organ health and the liver's vulnerability to developmental arsenic toxicity.
{"title":"Differential effects of gestational arsenic exposure on the liver and kidney of rat offspring across postnatal development","authors":"Daniel Silva Sena Bastos , Pedro Henrique de Carvalho Albuquerque de Souza , Mariana Machado-Neves , Luiz Otávio Guimarães-Ervilha , Leandro Licursi de Oliveira , Renê Chagas da Silva , Marcos Antônio José dos Santos , Wallace Martins de Araújo , Ana Cláudia Ferreira Souza","doi":"10.1016/j.fct.2025.115894","DOIUrl":"10.1016/j.fct.2025.115894","url":null,"abstract":"<div><div>Arsenic is a widespread environmental contaminant capable of crossing the placental barrier, posing risks to fetal development. This study evaluated the long-term effects of prenatal arsenic exposure on the liver and kidney of male Wistar rat offspring at prepubertal (PND15), peripubertal (PND28, 44) and adult (PND70) stages. Pregnant rats received 10 mg/L sodium arsenite in drinking water from gestational day 1 until parturition. Results revealed that prenatal arsenic exposure led to growth restriction until peripuberty and persistent arsenic accumulation in both organs. In the liver, significant alterations included increased serum AST and ALP, and disrupted SOD and CAT activity at different ages. These alterations were accompanied by elevated protein carbonylation and histopathological changes such as inflammation, vascular congestion and hydropic degeneration, especially at peripubertal and adult stages. In contrast, the kidney exhibited enhanced SOD and GST activity without corresponding increases in oxidative damage markers or histopathological lesions, despite some micromineral imbalances. Overall, the liver emerged as the primary target of prenatal arsenic-induced toxicity, whereas the kidney showed increased antioxidant enzyme activity in the absence of overt damage. These findings highlight the importance of intrauterine exposure timing in determining postnatal organ health and the liver's vulnerability to developmental arsenic toxicity.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"208 ","pages":"Article 115894"},"PeriodicalIF":3.5,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145740329","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 : 2025-12-09DOI: 10.1016/j.fct.2025.115896
Yasaman Etemadi , Jephte Y. Akakpo , Timothy A. Fields , Anup Ramachandran , Hartmut Jaeschke
Acetaminophen (APAP) overdose is a leading cause of acute liver failure (ALF), with acute kidney injury (AKI) increasing morbidity and mortality. N-acetylcysteine (NAC) prevents APAP-induced liver damage, but not AKI, highlighting the need to address differential inter-organ responses to APAP toxicity. We investigated the relationship between hepatic glutathione (GSH) depletion, liver injury, and subsequent kidney damage following APAP overdose. Male C57BL/6J mice received either moderate (300 mg/kg) or severe (600 mg/kg) overdoses of APAP, with or without buthionine sulfoximine (BSO, 50 mg/kg) to deplete GSH, or NAC (500 mg/kg) to replenish GSH. A moderate APAP overdose elevated liver injury markers (alanine aminotransferase, ALT) without significantly affecting blood urea nitrogen (BUN) levels, though kidney injury molecule-1 (KIM-1) expression increased. A severe overdose significantly increased ALT activities, and BUN and creatine levels, together with marked upregulation of renal KIM-1 and histological evidence of cortical damage. BSO exacerbated APAP-induced kidney but not liver injury, where GSH remained depleted at 24 h. In contrast, NAC protected against APAP hepatotoxicity but not AKI. Thus, these findings demonstrate critical organ-specific responses to APAP toxicity and underscore the need for targeted therapeutic strategies specifically addressing APAP-induced kidney injury.
{"title":"Differential effects on acetaminophen-induced nephrotoxicity and liver injury following modulation of glutathione resynthesis","authors":"Yasaman Etemadi , Jephte Y. Akakpo , Timothy A. Fields , Anup Ramachandran , Hartmut Jaeschke","doi":"10.1016/j.fct.2025.115896","DOIUrl":"10.1016/j.fct.2025.115896","url":null,"abstract":"<div><div>Acetaminophen (APAP) overdose is a leading cause of acute liver failure (ALF), with acute kidney injury (AKI) increasing morbidity and mortality. N-acetylcysteine (NAC) prevents APAP-induced liver damage, but not AKI, highlighting the need to address differential inter-organ responses to APAP toxicity. We investigated the relationship between hepatic glutathione (GSH) depletion, liver injury, and subsequent kidney damage following APAP overdose. Male C57BL/6J mice received either moderate (300 mg/kg) or severe (600 mg/kg) overdoses of APAP, with or without buthionine sulfoximine (BSO, 50 mg/kg) to deplete GSH, or NAC (500 mg/kg) to replenish GSH. A moderate APAP overdose elevated liver injury markers (alanine aminotransferase, ALT) without significantly affecting blood urea nitrogen (BUN) levels, though kidney injury molecule-1 (KIM-1) expression increased. A severe overdose significantly increased ALT activities, and BUN and creatine levels, together with marked upregulation of renal KIM-1 and histological evidence of cortical damage. BSO exacerbated APAP-induced kidney but not liver injury, where GSH remained depleted at 24 h. In contrast, NAC protected against APAP hepatotoxicity but not AKI. Thus, these findings demonstrate critical organ-specific responses to APAP toxicity and underscore the need for targeted therapeutic strategies specifically addressing APAP-induced kidney injury.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"208 ","pages":"Article 115896"},"PeriodicalIF":3.5,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145740253","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 : 2025-12-08DOI: 10.1016/j.fct.2025.115887
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, 3-methyl-2-butenyl acetate, CAS Registry Number 1191-16-8","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.2025.115887","DOIUrl":"10.1016/j.fct.2025.115887","url":null,"abstract":"","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"210 ","pages":"Article 115887"},"PeriodicalIF":3.5,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145720137","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":"Respond to the letter submitted to the editor entitled “Beyond monitoring: Integrating risk, benefit, and biomonitoring in Greek dietary exposure to dioxins and PCBs” by Parthe Aphale et al. regarding our publication by Costopoulou et al. titled “Dioxin and PCB monitoring in Greek food products during the period 2002–2022 and preliminary assessment of general population exposure through the diet” (Food Chem Toxicol. 2025;206:115717)","authors":"Danae Costopoulou, Irene Vassiliadou, Kleopatra Kedikoglou, Constantina Grigoriou, Leondios Leondiadis","doi":"10.1016/j.fct.2025.115845","DOIUrl":"10.1016/j.fct.2025.115845","url":null,"abstract":"","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"208 ","pages":"Article 115845"},"PeriodicalIF":3.5,"publicationDate":"2025-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145712825","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 : 2025-12-05DOI: 10.1016/j.fct.2025.115889
Fangli Zhao , Xiaoxia Zhou , Junyi Chen , Ruihua Li , Yan Sun , Jingyi Zhou , Hailun Li , Guangzhen Zheng , Lihong Zhu
This study aimed to reveal the key proteins and specific mechanisms of diclofenac-induced acute kidney injury (AKI) and to explore its potential antagonists based on a comprehensive technology of network toxicology, computer-aided virtual screening (including molecular docking and molecular dynamics simulations), and experimental validation. First, diclofenac was demonstrated to exhibit toxicity primarily associated with nephrotoxicity by ADMETlab 3.0. Afterwards, network toxicology approaches identified 25 core targets associated with diclofenac-induced AKI, such as CTSB, ALB, and AKT1. GO analysis showed a significant enrichment in biological processes, such as mitochondria and enzyme binding, while KEGG pathway analysis indicated that endocrine resistance played a critical role. Subsequently, computer-aided virtual screening identified that quercetin, a widely distributed dietary compound, may have potential as an antagonist pending further validation. Subsequent experimental validation in HK-2 cells demonstrated that quercetin not only improved the secretion of inflammatory cytokines in diclofenac-induced HK-2 cells but also reversed the abnormal expression of core proteins. Correlation analysis further validated the close relationship between these protective effects. In conclusion, diclofenac may induce AKI through a network of core targets such as CTSB, ALB, and AKT1, and natural active compounds such as quercetin represented promising antagonists for mitigating this drug-induced nephrotoxicity.
{"title":"Mechanistic insights into diclofenac-induced acute kidney injury and its antagonists identification","authors":"Fangli Zhao , Xiaoxia Zhou , Junyi Chen , Ruihua Li , Yan Sun , Jingyi Zhou , Hailun Li , Guangzhen Zheng , Lihong Zhu","doi":"10.1016/j.fct.2025.115889","DOIUrl":"10.1016/j.fct.2025.115889","url":null,"abstract":"<div><div>This study aimed to reveal the key proteins and specific mechanisms of diclofenac-induced acute kidney injury (AKI) and to explore its potential antagonists based on a comprehensive technology of network toxicology, computer-aided virtual screening (including molecular docking and molecular dynamics simulations), and experimental validation. First, diclofenac was demonstrated to exhibit toxicity primarily associated with nephrotoxicity by ADMETlab 3.0. Afterwards, network toxicology approaches identified 25 core targets associated with diclofenac-induced AKI, such as CTSB, ALB, and AKT1. GO analysis showed a significant enrichment in biological processes, such as mitochondria and enzyme binding, while KEGG pathway analysis indicated that endocrine resistance played a critical role. Subsequently, computer-aided virtual screening identified that quercetin, a widely distributed dietary compound, may have potential as an antagonist pending further validation. Subsequent experimental validation in HK-2 cells demonstrated that quercetin not only improved the secretion of inflammatory cytokines in diclofenac-induced HK-2 cells but also reversed the abnormal expression of core proteins. Correlation analysis further validated the close relationship between these protective effects. In conclusion, diclofenac may induce AKI through a network of core targets such as CTSB, ALB, and AKT1, and natural active compounds such as quercetin represented promising antagonists for mitigating this drug-induced nephrotoxicity.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"208 ","pages":"Article 115889"},"PeriodicalIF":3.5,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145699284","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 : 2025-12-05DOI: 10.1016/j.fct.2025.115886
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
γ-Hexalactone was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, photoirritation/photoallergenicity, skin sensitization, and environmental safety. Data from read-across analog γ-valerolactone (CAS # 108-29-2) show that γ-hexalactone is not expected to be genotoxic. Data on γ-hexalactone provide a calculated Margin of Exposure (MOE) > 100 for the repeated dose toxicity and developmental toxicity endpoints. Data on read-across analog γ-dodecalactone (CAS # 2305-05-7) provide a calculated MOE >100 for the fertility endpoint. Data from read-across analog 4-hydroxybutanoic acid lactone (CAS # 96-48-0) show that there are no safety concerns for γ-hexalactone for skin sensitization under the current declared levels of use. The photoirritation/photoallergenicity endpoints were evaluated based on ultraviolet/visible (UV/Vis) spectra; γ-hexalactone is not expected to be photoirritating/photoallergenic. The local respiratory toxicity endpoint was evaluated using the Threshold of Toxicological Concern (TTC) for a Cramer Class I material, and the exposure to γ-hexalactone is below the TTC (1.4 mg/day). The environmental endpoints were evaluated; γ-hexalactone 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.
{"title":"Update to RIFM fragrance ingredient safety assessment, γ-hexalactone, CAS Registry Number 695-06-7","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.2025.115886","DOIUrl":"10.1016/j.fct.2025.115886","url":null,"abstract":"<div><div>γ-Hexalactone was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, photoirritation/photoallergenicity, skin sensitization, and environmental safety. Data from read-across analog γ-valerolactone (CAS # 108-29-2) show that γ-hexalactone is not expected to be genotoxic. Data on γ-hexalactone provide a calculated Margin of Exposure (MOE) > 100 for the repeated dose toxicity and developmental toxicity endpoints. Data on read-across analog γ-dodecalactone (CAS # 2305-05-7) provide a calculated MOE >100 for the fertility endpoint. Data from read-across analog 4-hydroxybutanoic acid lactone (CAS # 96-48-0) show that there are no safety concerns for γ-hexalactone for skin sensitization under the current declared levels of use. The photoirritation/photoallergenicity endpoints were evaluated based on ultraviolet/visible (UV/Vis) spectra; γ-hexalactone is not expected to be photoirritating/photoallergenic. The local respiratory toxicity endpoint was evaluated using the Threshold of Toxicological Concern (TTC) for a Cramer Class I material, and the exposure to γ-hexalactone is below the TTC (1.4 mg/day). The environmental endpoints were evaluated; γ-hexalactone 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":"210 ","pages":"Article 115886"},"PeriodicalIF":3.5,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145699270","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 : 2025-12-05DOI: 10.1016/j.fct.2025.115891
Harin Jo , Subin Yoon , Sumin Cho , Eunji Lee , NaHyun Kim , Eun-Bin Choi , Inyoung Park , SiYeong Park , Na Yun Lee , Young Jeon , Hyeok-Won An , Jun Won Park , Gyochang Keum , Jae-Hwan Nam , Jun-Won Yun
Although mRNA vaccines have been pivotal in combating the COVID-19 pandemic, research on their side effects remains limited. Adverse effects can vary considerably, including cardiac injury, and individuals with diabetes may experience broader reactions. This study compared vehicle (Veh) and streptozotocin (STZ)-induced type 1 diabetes mellitus (T1DM) mouse models following administration of the novel SARS-CoV-2 mRNA vaccine candidate CUK3-1/LNP128 to evaluate its toxicity profile and assess potential adverse effects in the presence of underlying disease. Flow cytometry, enzyme-linked immunosorbent assay, and enzyme-linked immunospot analyses showed comparable activation of Th1 and cytotoxic T cell responses in both groups. Hematological analysis revealed increased neutrophil and decreased lymphocyte counts after vaccination, with no significant differences between groups. Veh and STZ mice exhibited elevated c-Troponin-I levels, indicative of myocardial injury, with a greater increase observed in STZ mice. Aspartate aminotransferase and lactate dehydrogenase levels were also higher in STZ mice, suggesting enhanced cardiotoxic potential. Notably, in parallel with elevated malondialdehyde levels and 4-hydroxynonenal immunoreactivity, cardiac protein levels of COX2, NF-κB, TNF-α, IL-1β, IL-6, and IL-12a were significantly higher in vaccinated STZ mice. These findings indicate that CUK3-1/LNP128 may exacerbate cardiotoxicity in T1DM, underscoring the need for careful monitoring of adverse effects in these patients.
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