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Zearalenone-14-Glucoside Is Hydrolyzed to Zearalenone by ß-Glucosidase in Extracellular Matrix to Exert Intracellular Toxicity in KGN Cells.
Ruan, Haonan; Wang, Yunyun; Hou, Yong; Zhang, Jing; Wu, Jiashuo; Zhang, Fangqing; Sui, Ming; Luo, Jiaoyang; Yang, Meihua.
Afiliação
  • Ruan H; Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China.
  • Wang Y; Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China.
  • Hou Y; Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China.
  • Zhang J; Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China.
  • Wu J; Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China.
  • Zhang F; Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China.
  • Sui M; Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China.
  • Luo J; Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China.
  • Yang M; Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China.
Toxins (Basel) ; 14(7)2022 07 04.
Article em En | MEDLINE | ID: mdl-35878196
ABSTRACT
As one of the most important conjugated mycotoxins, zearalenone-14-glucoside (Z14G) has received widespread attention from researchers. Although the metabolism of Z14G in animals has been extensively studied, the intracellular toxicity and metabolic process of Z14G are not fully elucidated. In this study, the cytotoxicity of Z14G to human ovarian granulosa cells (KGN) and the metabolism of Z14G in KGN cells were determined. Furthermore, the experiments of co-administration of ß-glucosidase and pre-administered ß-glucosidase inhibitor (Conduritol B epoxide, CBE) were used to clarify the mechanism of Z14G toxicity release. Finally, the human colon adenocarcinoma cell (Caco-2) metabolism model was used to verify the toxicity release mechanism of Z14G. The results showed that the IC50 of Z14G for KGN cells was 420 µM, and the relative hydrolysis rate of Z14G on ZEN was 35% (25% extracellular and 10% intracellular in KGN cells). The results indicated that Z14G cannot enter cells, and Z14G is only hydrolyzed extracellularly to its prototype zearalenone (ZEN) by ß-glucosidase which can exert toxic effects in cells. In conclusion, this study demonstrated the cytotoxicity of Z14G and clarified the toxicity release mechanism of Z14G. Different from previous findings, our results showed that Z14G cannot enter cells but exerts cytotoxicity through deglycosylation. This study promotes the formulation of a risk assessment and legislation limit for ZEN and its metabolites.
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Texto completo: 1 Coleções: 01-internacional Temas: Geral / Tipos_de_cancer / Colon_e_reto Base de dados: MEDLINE Assunto principal: Zearalenona / Adenocarcinoma / Beta-Glucosidase / Neoplasias do Colo Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Female / Humans Idioma: En Revista: Toxins (Basel) Ano de publicação: 2022 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Coleções: 01-internacional Temas: Geral / Tipos_de_cancer / Colon_e_reto Base de dados: MEDLINE Assunto principal: Zearalenona / Adenocarcinoma / Beta-Glucosidase / Neoplasias do Colo Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Female / Humans Idioma: En Revista: Toxins (Basel) Ano de publicação: 2022 Tipo de documento: Article País de afiliação: China