Pub Date : 2025-02-16DOI: 10.1016/j.fct.2025.115319
Urooj Iqbal, Abdul Malik, Nabeela Tabassum Sial, Malik Hassan Mehmood, Ambreen Malik Uttra, Ume Ruqia Tulain, Alia Erum, Muhammad Fayyaz-Ur-Rehman, Nermeen N Welson, Mohamed H Mahmoud, Athanasios Alexiou, Marios Papadakis, Gaber El-Saber Bathia
In order to evaluate anti-inflammatory role of eucalyptol (100, 200, and 400 mg/kg orally), inflammation was induced in rats using 0.1 ml of histamine and 0.1 ml of formaldehyde. Furthermore, in vivo gastroprotective potential of eucalyptol (100, 200 and 400 mg/kg) was determined via the intraperitoneal injection of 25 mg/kg indomethacin as an ulcerative agent and omeprazole (30 mg/kg) orally as a standard. Estimation of biochemical (PGE2, ICAM-1, COX-I, COX-II, eNOS and 5-LOX) and oxidative stress (SOD, CAT, GSH, and MDA) markers were carried out in gastric tissues using ELISA. The morphological and histopathological features of the gastric tissues were studied. In vitro, eucalyptol stabilized red blood cell membranes and inhibited protein denaturation, with the maximum effect observed at a concentration of 6,400 μg/mL. Eucalyptol significantly reduced rat paw edema in histamine- and formaldehyde-induced inflammation models. It increased gastric PGE2, COX-I and eNOS levels, and decreased COX-II, 5-LOX and ICAM-1. Eucalyptol reduced ulcer indices and improved histopathological changes. Eucalyptol also increased antioxidants levels with decreased MDA levels in isolated rat stomach tissues. Therefore, eucalyptol shows gastroprotective effects against histamine- and formaldehyde induced inflammation and indomethacin-induced gastric ulcers through the modulation of the COX/LOX, ICAM-1, eNOS pathways and oxidative stress biomarkers.
{"title":"Eucalyptol Attenuates Indomethacin-Induced Gastric Ulcers in Rats by Modulating the ICAM-1, eNOS and COX/LOX Pathways: Insights from In Silico, In Vitro and In Vivo Approaches.","authors":"Urooj Iqbal, Abdul Malik, Nabeela Tabassum Sial, Malik Hassan Mehmood, Ambreen Malik Uttra, Ume Ruqia Tulain, Alia Erum, Muhammad Fayyaz-Ur-Rehman, Nermeen N Welson, Mohamed H Mahmoud, Athanasios Alexiou, Marios Papadakis, Gaber El-Saber Bathia","doi":"10.1016/j.fct.2025.115319","DOIUrl":"https://doi.org/10.1016/j.fct.2025.115319","url":null,"abstract":"<p><p>In order to evaluate anti-inflammatory role of eucalyptol (100, 200, and 400 mg/kg orally), inflammation was induced in rats using 0.1 ml of histamine and 0.1 ml of formaldehyde. Furthermore, in vivo gastroprotective potential of eucalyptol (100, 200 and 400 mg/kg) was determined via the intraperitoneal injection of 25 mg/kg indomethacin as an ulcerative agent and omeprazole (30 mg/kg) orally as a standard. Estimation of biochemical (PGE<sub>2,</sub> ICAM-1, COX-I, COX-II, eNOS and 5-LOX) and oxidative stress (SOD, CAT, GSH, and MDA) markers were carried out in gastric tissues using ELISA. The morphological and histopathological features of the gastric tissues were studied. In vitro, eucalyptol stabilized red blood cell membranes and inhibited protein denaturation, with the maximum effect observed at a concentration of 6,400 μg/mL. Eucalyptol significantly reduced rat paw edema in histamine- and formaldehyde-induced inflammation models. It increased gastric PGE<sub>2,</sub> COX-I and eNOS levels, and decreased COX-II, 5-LOX and ICAM-1. Eucalyptol reduced ulcer indices and improved histopathological changes. Eucalyptol also increased antioxidants levels with decreased MDA levels in isolated rat stomach tissues. Therefore, eucalyptol shows gastroprotective effects against histamine- and formaldehyde induced inflammation and indomethacin-induced gastric ulcers through the modulation of the COX/LOX, ICAM-1, eNOS pathways and oxidative stress biomarkers.</p>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":" ","pages":"115319"},"PeriodicalIF":3.9,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447573","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 : 2025-02-15DOI: 10.1016/j.fct.2025.115322
Samah S Arafa, Heba A Elnoury, Sahar Badr El-Din, Mohamed A Sakr, Fatma Fawzi Hendawi, Rehab Ali Elsayed Masoud, Samia Soliman Barghash, Doaa Sabry Elbehairy, Ayat Abdelaty Hemeda, Islam Mostafa Farrag, Doaa Sayed Abdelrahman, Amira Mohammad Elsadek, Sahar K Ghanem, Hind S AboShabaan, Ahmed M Atwa, Mahmoud Nour El Din, Abdullah F Radwan, Majid Al-Zahrani, Ahmad F Alhomodi, Ahmed M Abdulfattah, Afaf Abdelkader
Acetamiprid (ACE) is a neonicotinoid insecticide with widespread global application, resulting in persistent human exposure. The current research examined the toxicological implications of ACE exposure on human lung fibroblasts (MRC-5 cells) and bronchial epithelial cells (BEAS-2B cells). The following implications were explored: oxidative stress, epithelial-mesenchymal transition, apoptosis, cellular proliferation, and extracellular matrix accumulation. The prospective protective properties of heat-killed Lactobacillus fermentum and Lactobacillus delbrueckii (HKL) were further studied. The 14-day exposure to ACE at 4 μM triggered oxidative stress and inflammation. ACE promoted epithelial-mesenchymal transition, as evidenced by the decline of protein and mRNA abundances of E-cadherin alongside increased protein and mRNA quantities of α-SMA and N-cadherin in BEAS-2B cells. Additionally, it elicited apoptosis in BEAS-2B cells and stimulated the cellular growth of MRC-5 cells. The TGF-β1/ Smad pathway was activated upon ACE exposure, leading to the accumulation of extracellular matrix. HKL demonstrated antioxidant, anti-apoptotic, anti-proliferative, and anti-fibrotic properties, mitigating ACE-induced toxicity. Our findings delineate the molecular mechanisms underlying epithelial-mesenchymal transition, inflammation, oxidative stress, and extracellular matrix accumulation in ACE-induced pulmonary fibrosis, which provides new insights into pulmonary injury. Additionally, this investigation would offer us an approach to mitigate lung deterioration induced by ACE through utilizing heat-killed probiotic supplementation.
{"title":"Acetamiprid-induced pulmonary toxicity via oxidative stress, epithelial-mesenchymal transition, apoptosis, and extracellular matrix accumulation in human lung epithelial cells and fibroblasts: Protective role of heat-killed Lactobacilli.","authors":"Samah S Arafa, Heba A Elnoury, Sahar Badr El-Din, Mohamed A Sakr, Fatma Fawzi Hendawi, Rehab Ali Elsayed Masoud, Samia Soliman Barghash, Doaa Sabry Elbehairy, Ayat Abdelaty Hemeda, Islam Mostafa Farrag, Doaa Sayed Abdelrahman, Amira Mohammad Elsadek, Sahar K Ghanem, Hind S AboShabaan, Ahmed M Atwa, Mahmoud Nour El Din, Abdullah F Radwan, Majid Al-Zahrani, Ahmad F Alhomodi, Ahmed M Abdulfattah, Afaf Abdelkader","doi":"10.1016/j.fct.2025.115322","DOIUrl":"https://doi.org/10.1016/j.fct.2025.115322","url":null,"abstract":"<p><p>Acetamiprid (ACE) is a neonicotinoid insecticide with widespread global application, resulting in persistent human exposure. The current research examined the toxicological implications of ACE exposure on human lung fibroblasts (MRC-5 cells) and bronchial epithelial cells (BEAS-2B cells). The following implications were explored: oxidative stress, epithelial-mesenchymal transition, apoptosis, cellular proliferation, and extracellular matrix accumulation. The prospective protective properties of heat-killed Lactobacillus fermentum and Lactobacillus delbrueckii (HKL) were further studied. The 14-day exposure to ACE at 4 μM triggered oxidative stress and inflammation. ACE promoted epithelial-mesenchymal transition, as evidenced by the decline of protein and mRNA abundances of E-cadherin alongside increased protein and mRNA quantities of α-SMA and N-cadherin in BEAS-2B cells. Additionally, it elicited apoptosis in BEAS-2B cells and stimulated the cellular growth of MRC-5 cells. The TGF-β1/ Smad pathway was activated upon ACE exposure, leading to the accumulation of extracellular matrix. HKL demonstrated antioxidant, anti-apoptotic, anti-proliferative, and anti-fibrotic properties, mitigating ACE-induced toxicity. Our findings delineate the molecular mechanisms underlying epithelial-mesenchymal transition, inflammation, oxidative stress, and extracellular matrix accumulation in ACE-induced pulmonary fibrosis, which provides new insights into pulmonary injury. Additionally, this investigation would offer us an approach to mitigate lung deterioration induced by ACE through utilizing heat-killed probiotic supplementation.</p>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":" ","pages":"115322"},"PeriodicalIF":3.9,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143439524","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 : 2025-02-14DOI: 10.1016/j.fct.2025.115320
A.M. Api , A. Bartlett , D. Belsito , D. Botelho , M. Bruze , A. Bryant-Friedrich , G.A. Burton Jr. , M.A. Cancellieri , H. Chon , M.L. Dagli , W. Dekant , C. Deodhar , K. Farrell , A.D. Fryer , L. Jones , K. Joshi , A. Lapczynski , M. Lavelle , I. Lee , H. Moustakas , Y. Tokura
{"title":"Update to RIFM fragrance ingredient safety assessment, methyl 3,7-dimethyl-6-octenoate, CAS registry number 2270-60-2","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.L. Dagli , W. Dekant , C. Deodhar , K. Farrell , A.D. Fryer , L. Jones , K. Joshi , A. Lapczynski , M. Lavelle , I. Lee , H. Moustakas , Y. Tokura","doi":"10.1016/j.fct.2025.115320","DOIUrl":"10.1016/j.fct.2025.115320","url":null,"abstract":"","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"197 ","pages":"Article 115320"},"PeriodicalIF":3.9,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143427539","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 : 2025-02-14DOI: 10.1016/j.fct.2025.115323
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, cyclohexanepropanol, α-ethyl-2,2,6-trimethyl-, CAS Registry Number 60241-52-3.","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.2025.115323","DOIUrl":"https://doi.org/10.1016/j.fct.2025.115323","url":null,"abstract":"","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":" ","pages":"115323"},"PeriodicalIF":3.9,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143432062","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 : 2025-02-13DOI: 10.1016/j.fct.2025.115321
A.M. Api , A. Bartlett , D. Belsito , D. Botelho , M. Bruze , A. Bryant-Friedrich , G.A. Burton Jr. , M.A. Cancellieri , H. Chon , M.L. Dagli , W. Dekant , C. Deodhar , K. Farrell , A.D. Fryer , L. Jones , K. Joshi , A. Lapczynski , M. Lavelle , I. Lee , H. Moustakas , Y. Tokura
{"title":"RIFM fragrance ingredient safety assessment, (1aα,4α,7aα)-1a,3,3,4,6,6-hexamethyl-1a,2,3,4,5,6,7,7a-octahydronapth[3,3-b]oxirene, CAS Registry Number 94400-98-3","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.L. Dagli , W. Dekant , C. Deodhar , K. Farrell , A.D. Fryer , L. Jones , K. Joshi , A. Lapczynski , M. Lavelle , I. Lee , H. Moustakas , Y. Tokura","doi":"10.1016/j.fct.2025.115321","DOIUrl":"10.1016/j.fct.2025.115321","url":null,"abstract":"","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"197 ","pages":"Article 115321"},"PeriodicalIF":3.9,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424424","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 : 2025-02-13DOI: 10.1016/j.fct.2025.115324
Ziyang Huang , Ruijia Xu , Zhongjun Wan , Chao Liu , Jinquan Li , Jun He , Li Li
Cadmium (Cd) is a prevalent heavy metal pollutant known to cause lung damage. However, the mechanisms underlying Cd-induced lung injury and the associated therapeutic strategies remain unclear. By establishing Cd-induced lung damage models both in vivo and in vitro, we observed that Cd inhibited the Nrf2/HO-1 signaling pathway, disrupted the redox balance in lung tissue, accelerated endoplasmic reticulum (ER) stress, and promoted ferroptosis, ultimately leading to lung injury. Melatonin (Mel), a potent reactive oxygen species (ROS) inhibitor with high antioxidative efficacy, mitigated the increasing in ROS and the decreasing in superoxide dismutase levels induced by Cd, as well as the upregulation of PERK-eIF2α-ATF4 signaling associated with ER stress, through the activation of the Nrf2/HO-1 signaling pathway. Furthermore, Mel administration not only prevented Cd-induced iron overload but also reduced lipid peroxidation levels, thereby improving mitochondrial morphological alterations. Collectively, our results demonstrated that Mel treatment alleviated Cd-induced lung injury by inhibiting oxidative stress, which in turn ameliorated ER stress and ferroptosis through the activation of the Nrf2/HO-1 pathway.
{"title":"Melatonin protects against cadmium-induced endoplasmic reticulum stress and ferroptosis through activating Nrf2/HO-1 signaling pathway in mice lung","authors":"Ziyang Huang , Ruijia Xu , Zhongjun Wan , Chao Liu , Jinquan Li , Jun He , Li Li","doi":"10.1016/j.fct.2025.115324","DOIUrl":"10.1016/j.fct.2025.115324","url":null,"abstract":"<div><div>Cadmium (Cd) is a prevalent heavy metal pollutant known to cause lung damage. However, the mechanisms underlying Cd-induced lung injury and the associated therapeutic strategies remain unclear. By establishing Cd-induced lung damage models both <em>in vivo and in vitro</em>, we observed that Cd inhibited the Nrf2/HO-1 signaling pathway, disrupted the redox balance in lung tissue, accelerated endoplasmic reticulum (ER) stress, and promoted ferroptosis, ultimately leading to lung injury. Melatonin (Mel), a potent reactive oxygen species (ROS) inhibitor with high antioxidative efficacy, mitigated the increasing in ROS and the decreasing in superoxide dismutase levels induced by Cd, as well as the upregulation of PERK-eIF2α-ATF4 signaling associated with ER stress, through the activation of the Nrf2/HO-1 signaling pathway. Furthermore, Mel administration not only prevented Cd-induced iron overload but also reduced lipid peroxidation levels, thereby improving mitochondrial morphological alterations. Collectively, our results demonstrated that Mel treatment alleviated Cd-induced lung injury by inhibiting oxidative stress, which in turn ameliorated ER stress and ferroptosis through the activation of the Nrf2/HO-1 pathway.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"198 ","pages":"Article 115324"},"PeriodicalIF":3.9,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424470","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 : 2025-02-12DOI: 10.1016/j.fct.2025.115318
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":"RIFM fragrance ingredient safety assessment, cyclododecyl formate, CAS Registry Number 59052-82-3","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.2025.115318","DOIUrl":"10.1016/j.fct.2025.115318","url":null,"abstract":"","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"197 ","pages":"Article 115318"},"PeriodicalIF":3.9,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143419775","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 : 2025-02-10DOI: 10.1016/j.fct.2025.115317
Wentai Wang , Na Yang , Junlin Yang , Jiaojiao He , Guohui Bai , Chenglong Tu
Prevalence of fluoride and sulfur dioxide (SO2) cocontamination in the environment poses a serious threat to various human organs, especially the teeth. However, direct evidence linking coexposure to fluoride and SO2 with enamel mineralization disorders is lacking. Here, we investigated the mechanisms through which fluoride and SO2 exposure, either alone or in combination, affects enamel mineralization in mouse and LS8 cell models. Coexposure to fluoride and SO2 resulted in more severe enamel mineralization disorders compared with those in the control or individual exposure groups. The coexposure caused significant pathological changes and retention of enamel matrix. Furthermore, the coexposure upregulated the expression of membrane calcium channels (Cav1.2), calmodulin-dependent protein kinase II (CaMKII), endoplasmic reticulum calcium ion(Ca2+)-release channel (IP3R), and endoplasmic reticulum stress (ERS) marker protein (GRP78), and significantly downregulated the expression of endoplasmic reticulum (ER) Ca2+-uptake pump protein (SERCA2) and calreticulin (CRT). Investigations using Amlodipine (Am), Tunicamycin (Tm) and CDN1163 revealed that the coexposure exacerbated enamel mineralization disorders by disrupting calcium homeostasis and subsequently triggering ERS. Overall, this study highlights that coexposure to fluoride and SO2 affects ER Ca2+ content through cytoplasmic calcium overload, triggers ERS, and increases the risk of enamel mineralization disorders. Activation of ERS, induced by disruption of calcium homeostasis, may play a key role in fluoride and SO2-induced enamel mineralization disorders. The insights obtained from this study should be valuable for devising strategies to mitigate the effects of fluoride and SO2 coexposure on enamel mineralization disorders.
{"title":"Coexposure to fluoride and sulfur dioxide aggravates enamel mineralization disorders in mice by disrupting calcium homeostasis-mediated endoplasmic reticulum stress","authors":"Wentai Wang , Na Yang , Junlin Yang , Jiaojiao He , Guohui Bai , Chenglong Tu","doi":"10.1016/j.fct.2025.115317","DOIUrl":"10.1016/j.fct.2025.115317","url":null,"abstract":"<div><div>Prevalence of fluoride and sulfur dioxide (SO<sub>2</sub>) cocontamination in the environment poses a serious threat to various human organs, especially the teeth. However, direct evidence linking coexposure to fluoride and SO<sub>2</sub> with enamel mineralization disorders is lacking. Here, we investigated the mechanisms through which fluoride and SO<sub>2</sub> exposure, either alone or in combination, affects enamel mineralization in mouse and LS8 cell models. Coexposure to fluoride and SO<sub>2</sub> resulted in more severe enamel mineralization disorders compared with those in the control or individual exposure groups. The coexposure caused significant pathological changes and retention of enamel matrix. Furthermore, the coexposure upregulated the expression of membrane calcium channels (Cav1.2), calmodulin-dependent protein kinase II (CaMKII), endoplasmic reticulum calcium ion(Ca<sup>2+</sup>)-release channel (IP<sub>3</sub>R), and endoplasmic reticulum stress (ERS) marker protein (GRP78), and significantly downregulated the expression of endoplasmic reticulum (ER) Ca<sup>2+</sup>-uptake pump protein (SERCA2) and calreticulin (CRT). Investigations using Amlodipine (Am), Tunicamycin (Tm) and CDN1163 revealed that the coexposure exacerbated enamel mineralization disorders by disrupting calcium homeostasis and subsequently triggering ERS. Overall, this study highlights that coexposure to fluoride and SO<sub>2</sub> affects ER Ca<sup>2+</sup> content through cytoplasmic calcium overload, triggers ERS, and increases the risk of enamel mineralization disorders. Activation of ERS, induced by disruption of calcium homeostasis, may play a key role in fluoride and SO<sub>2</sub>-induced enamel mineralization disorders. The insights obtained from this study should be valuable for devising strategies to mitigate the effects of fluoride and SO<sub>2</sub> coexposure on enamel mineralization disorders.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"198 ","pages":"Article 115317"},"PeriodicalIF":3.9,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143404996","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 : 2025-02-09DOI: 10.1016/j.fct.2025.115315
Vanessa Partsch , Francesco Crudo , Daniel Piller , Elisabeth Varga , Giorgia Del Favero , Doris Marko
Alternaria mycotoxins may pose significant risks to human health due to their diverse spectrum of adverse effects and frequent occurrences in food. A previous study demonstrated the immunosuppressive, antiestrogenic, and genotoxic potential of a complex Alternaria mycotoxin extract (CE). The present study aimed to elucidate specific Alternaria mycotoxins or combinations thereof responsible for toxicity.
Following toxicity-guided fractionation of the CE, a multiparametric panel of assays was applied to assess different endpoints. These included immunomodulatory effects (NF-κB reporter gene assay in THP1-Lucia™ monocytes), estrogenicity/antiestrogenicity (alkaline phosphatase assay in Ishikawa cells) and genotoxicity (γH2AX and alkaline comet assays in HepG2 cells).
LC-MS/MS analysis revealed prominent mycotoxins in the active fractions, with altersetin (AST) identified as a novel key compound exhibiting immunoinhibitory (≥2 μM) and antiestrogenic (≥5 μM) properties in vitro. Additionally, while specific mycotoxin combinations explained the toxicity of active fractions, some effects remained unexplained, suggesting the presence of unidentified bioactive substances.
This study underscores the significance of AST and specific toxin mixtures as major contributors to CE toxicity. Further, it highlights the importance of considering combinatory effects in risk assessment of Alternaria mycotoxins as well as further investigation of unknown Alternaria metabolites, which may pose additional health risks.
{"title":"Resolving complexity: Identification of altersetin and toxin mixtures responsible for the immunomodulatory, antiestrogenic and genotoxic potential of a complex Alternaria mycotoxin extract","authors":"Vanessa Partsch , Francesco Crudo , Daniel Piller , Elisabeth Varga , Giorgia Del Favero , Doris Marko","doi":"10.1016/j.fct.2025.115315","DOIUrl":"10.1016/j.fct.2025.115315","url":null,"abstract":"<div><div><em>Alternaria</em> mycotoxins may pose significant risks to human health due to their diverse spectrum of adverse effects and frequent occurrences in food. A previous study demonstrated the immunosuppressive, antiestrogenic, and genotoxic potential of a complex <em>Alternaria</em> mycotoxin extract (CE). The present study aimed to elucidate specific <em>Alternaria</em> mycotoxins or combinations thereof responsible for toxicity.</div><div>Following toxicity-guided fractionation of the CE, a multiparametric panel of assays was applied to assess different endpoints. These included immunomodulatory effects (NF-κB reporter gene assay in THP1-Lucia™ monocytes), estrogenicity/antiestrogenicity (alkaline phosphatase assay in Ishikawa cells) and genotoxicity (γH2AX and alkaline comet assays in HepG2 cells).</div><div>LC-MS/MS analysis revealed prominent mycotoxins in the active fractions, with altersetin (AST) identified as a novel key compound exhibiting immunoinhibitory (≥2 μM) and antiestrogenic (≥5 μM) properties <em>in vitro</em>. Additionally, while specific mycotoxin combinations explained the toxicity of active fractions, some effects remained unexplained, suggesting the presence of unidentified bioactive substances.</div><div>This study underscores the significance of AST and specific toxin mixtures as major contributors to CE toxicity. Further, it highlights the importance of considering combinatory effects in risk assessment of <em>Alternaria</em> mycotoxins as well as further investigation of unknown <em>Alternaria</em> metabolites, which may pose additional health risks.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"198 ","pages":"Article 115315"},"PeriodicalIF":3.9,"publicationDate":"2025-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143397686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-08DOI: 10.1016/j.fct.2025.115316
Bo Peng, Xinyi Zhu, Li Geng, Wenping Xu, Jiagao Cheng, Liming Tao, Yang Zhang
This study evaluates the developmental and cardiotoxic effects of cyhalofop-butyl, a commonly used herbicide in rice agriculture, on zebrafish (Danio rerio) embryos. Despite its widespread application, the risk assessment of cyhalofop-butyl for aquatic organisms, especially fish, is still lacking. Focusing on the cardiac system, we used a zebrafish model to evaluate developmental abnormalities, changes in cardiac morphology and function, markers of oxidative stress, and altered gene expression. The results suggest that cyhalofop-butyl induces oxidative stress, lipid accumulation, and apoptosis in zebrafish embryos. In addition, it can lead to abnormal embryonic development and cardiac morphological dysfunction (such as pericardial edema, decreased heart rate, and red blood cell (RBC) flow rate, and cardiac linearization). Cyhalofop-butyl also significantly alters the expression of cardiac-related genes, including myl7, vmhc, myh6, nkx2.5, tbx5, nppa, has2, and myh7. In summary, cyhalofop-butyl elicits both dysplasia and cardiotoxicity in zebrafish embryos, highlighting the need for further safety risk evaluation of this herbicide in aquatic ecosystems.
{"title":"Developmental and cardiotoxic effects of cyhalofop-butyl in zebrafish embryos","authors":"Bo Peng, Xinyi Zhu, Li Geng, Wenping Xu, Jiagao Cheng, Liming Tao, Yang Zhang","doi":"10.1016/j.fct.2025.115316","DOIUrl":"10.1016/j.fct.2025.115316","url":null,"abstract":"<div><div>This study evaluates the developmental and cardiotoxic effects of cyhalofop-butyl, a commonly used herbicide in rice agriculture, on zebrafish (<em>Danio rerio</em>) embryos. Despite its widespread application, the risk assessment of cyhalofop-butyl for aquatic organisms, especially fish, is still lacking. Focusing on the cardiac system, we used a zebrafish model to evaluate developmental abnormalities, changes in cardiac morphology and function, markers of oxidative stress, and altered gene expression. The results suggest that cyhalofop-butyl induces oxidative stress, lipid accumulation, and apoptosis in zebrafish embryos. In addition, it can lead to abnormal embryonic development and cardiac morphological dysfunction (such as pericardial edema, decreased heart rate, and red blood cell (RBC) flow rate, and cardiac linearization). Cyhalofop-butyl also significantly alters the expression of cardiac-related genes, including <em>myl7</em>, <em>vmhc</em>, <em>myh6</em>, <em>nkx2.5</em>, <em>tbx5</em>, <em>nppa</em>, <em>has2</em>, and <em>myh7</em>. In summary, cyhalofop-butyl elicits both dysplasia and cardiotoxicity in zebrafish embryos, highlighting the need for further safety risk evaluation of this herbicide in aquatic ecosystems.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"198 ","pages":"Article 115316"},"PeriodicalIF":3.9,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389792","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