Sudan II and IV induce liver carcinogenesis through interactions with AKR1D1 in computational and experimental studies insights from the Taiwan Sudan Red chili pepper incident
Sudan dyes, a group of synthetic azo dyes, are widely used in industrial applications despite their potential health hazards. Recent incidents, such as the Taiwan Sudan Red chili pepper contamination, have underscored significant food safety concerns and the need for a better understanding of these...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-09-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651325008425 |
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| author | Liangjing Zhou Chaolei Zhang Chengjie Xu Zongrong Chen Rui Chen Liping Cao Shengnan Jia |
| author_facet | Liangjing Zhou Chaolei Zhang Chengjie Xu Zongrong Chen Rui Chen Liping Cao Shengnan Jia |
| author_sort | Liangjing Zhou |
| collection | DOAJ |
| description | Sudan dyes, a group of synthetic azo dyes, are widely used in industrial applications despite their potential health hazards. Recent incidents, such as the Taiwan Sudan Red chili pepper contamination, have underscored significant food safety concerns and the need for a better understanding of these compounds' toxicity and pathogenic mechanisms. This study combines computational biology, bioinformatics, and experimental validation to investigate the pathogenic effects of Sudan I, II, III, and IV on liver-associated proteins and their potential contribution to liver carcinogenesis. We utilized AlphaFold2 and molecular docking to predict the binding interactions between Sudan dyes and key hepatic enzymes, particularly AKR1D1, and further assessed the stability of these interactions through molecular dynamics simulations. Results show that while CYP1A1 is involved in the oxidative metabolism of Sudan compounds, it fails to fully metabolize them, thereby allowing interaction with AKR1D1. Sudan II and IV, in particular, exhibited stable binding to AKR1D1, potentially contributing to bile acid accumulation and promoting liver cancer. In contrast, Sudan III demonstrated lower binding stability, suggesting alternative pathogenic pathways. Experimental analysis using HepG2 liver cancer cells confirmed the tumor-promoting effects of Sudan II and IV, while Sudan III exerted proliferative effects only at higher concentrations. These findings underscore the complexity of the interactions between Sudan compounds and liver proteins and highlight the need for continued research to clarify their health risks and develop targeted prevention strategies. |
| format | Article |
| id | doaj-art-94426854ae8b4cfc9d2eba50e8840d8f |
| institution | Kabale University |
| issn | 0147-6513 |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj-art-94426854ae8b4cfc9d2eba50e8840d8f2025-08-20T03:41:17ZengElsevierEcotoxicology and Environmental Safety0147-65132025-09-0130211849710.1016/j.ecoenv.2025.118497Sudan II and IV induce liver carcinogenesis through interactions with AKR1D1 in computational and experimental studies insights from the Taiwan Sudan Red chili pepper incidentLiangjing Zhou0Chaolei Zhang1Chengjie Xu2Zongrong Chen3Rui Chen4Liping Cao5Shengnan Jia6Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, ChinaDepartment of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, ChinaDepartment of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, ChinaDepartment of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, ChinaCollege of Life Sciences and Health Engineering, Jiangnan University, Wuxi, ChinaDepartment of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, China; Zhejiang Engineering Research Center of Cognitive Healthcare, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, China; Corresponding authors at: Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, China.Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, China; Zhejiang Engineering Research Center of Cognitive Healthcare, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, China; Corresponding authors at: Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, China.Sudan dyes, a group of synthetic azo dyes, are widely used in industrial applications despite their potential health hazards. Recent incidents, such as the Taiwan Sudan Red chili pepper contamination, have underscored significant food safety concerns and the need for a better understanding of these compounds' toxicity and pathogenic mechanisms. This study combines computational biology, bioinformatics, and experimental validation to investigate the pathogenic effects of Sudan I, II, III, and IV on liver-associated proteins and their potential contribution to liver carcinogenesis. We utilized AlphaFold2 and molecular docking to predict the binding interactions between Sudan dyes and key hepatic enzymes, particularly AKR1D1, and further assessed the stability of these interactions through molecular dynamics simulations. Results show that while CYP1A1 is involved in the oxidative metabolism of Sudan compounds, it fails to fully metabolize them, thereby allowing interaction with AKR1D1. Sudan II and IV, in particular, exhibited stable binding to AKR1D1, potentially contributing to bile acid accumulation and promoting liver cancer. In contrast, Sudan III demonstrated lower binding stability, suggesting alternative pathogenic pathways. Experimental analysis using HepG2 liver cancer cells confirmed the tumor-promoting effects of Sudan II and IV, while Sudan III exerted proliferative effects only at higher concentrations. These findings underscore the complexity of the interactions between Sudan compounds and liver proteins and highlight the need for continued research to clarify their health risks and develop targeted prevention strategies.http://www.sciencedirect.com/science/article/pii/S0147651325008425Sudan azo dyesAKR1D1HepatocarcinogenesisReverse virtual screeningMolecular docking and dynamics, Experimental validation |
| spellingShingle | Liangjing Zhou Chaolei Zhang Chengjie Xu Zongrong Chen Rui Chen Liping Cao Shengnan Jia Sudan II and IV induce liver carcinogenesis through interactions with AKR1D1 in computational and experimental studies insights from the Taiwan Sudan Red chili pepper incident Ecotoxicology and Environmental Safety Sudan azo dyes AKR1D1 Hepatocarcinogenesis Reverse virtual screening Molecular docking and dynamics, Experimental validation |
| title | Sudan II and IV induce liver carcinogenesis through interactions with AKR1D1 in computational and experimental studies insights from the Taiwan Sudan Red chili pepper incident |
| title_full | Sudan II and IV induce liver carcinogenesis through interactions with AKR1D1 in computational and experimental studies insights from the Taiwan Sudan Red chili pepper incident |
| title_fullStr | Sudan II and IV induce liver carcinogenesis through interactions with AKR1D1 in computational and experimental studies insights from the Taiwan Sudan Red chili pepper incident |
| title_full_unstemmed | Sudan II and IV induce liver carcinogenesis through interactions with AKR1D1 in computational and experimental studies insights from the Taiwan Sudan Red chili pepper incident |
| title_short | Sudan II and IV induce liver carcinogenesis through interactions with AKR1D1 in computational and experimental studies insights from the Taiwan Sudan Red chili pepper incident |
| title_sort | sudan ii and iv induce liver carcinogenesis through interactions with akr1d1 in computational and experimental studies insights from the taiwan sudan red chili pepper incident |
| topic | Sudan azo dyes AKR1D1 Hepatocarcinogenesis Reverse virtual screening Molecular docking and dynamics, Experimental validation |
| url | http://www.sciencedirect.com/science/article/pii/S0147651325008425 |
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