A novel glutathione-conjugates of deoxynivalenol biotransformation in vitro and the cytotoxic properties evaluation

文献类型： 外文期刊

第一作者： Zhang, Haosu

作者： Zhang, Haosu;Zheng, Siyan;Zuo, Yunhui;Yang, Jiguo;Tang, Yuqian;Yu, Yuanshan

作者机构：

关键词： Deoxynivalenol; DON-GSH conjugation; Glutathione S-transferase; Cytotoxicity

期刊名称：FOOD RESEARCH INTERNATIONAL （ 影响因子：8.0； 五年影响因子：8.5 ）

ISSN： 0963-9969

年卷期： 2025 年 214 卷

页码：

收录情况： SCI

摘要： A significant research breakthrough involving deoxynivalenol (DON) has uncovered a critical link between Fusarium head blight (FHB) contamination and glutathione (GSH) in plants. This interaction leads to the formation of diverse structural products, facilitated by glutathione S-transferase (GST), which plays a pivotal role in supporting plants' innate defense mechanisms. In this study, we describe the synthesis of a single DON-10-GSH conjugate at 4 degrees C and investigate the in vitro binding of GSH and DON under varying experimental conditions. After reacting DON with GSH in our in vitro system at 4 degrees C for 6 days, we confirmed that the thiol group of GSH reacts with the C10 double bond of DON. Concurrently, the ketone group at C8 was reduced to a hydroxyl group, which subsequently underwent aldol condensation with the hydroxyl group at C15, forming the hemiketal product DON-10-GSH. Lower concentrations of GSH were found to be more conducive to the glutathionylation of DON at 4 degrees C, with the highest binding rate observed at pH 6.5. Notably, no reaction between DON and GSH was detected at 12 degrees C, 25 degrees C, or 37 degrees C. Cell experiments demonstrated that the transformed product exhibited significantly reduced toxicity to HepG2 and Caco-2 cells compared to DON, without compromising the integrity of the integrity of the Caco-2 cell barrier. Additionally, catalyzing the reaction with four distinct sources of GST (0.1 U/mL) for 4 days significantly increased the binding rate, with the most effective GST achieving 86 % binding of DON (20 mu g/mL) to GSH in vitro. The glutathione conjugation process utilizes the thiol group of GSH to couple with electrophilic sites on DON, enhancing DON's hydrophobicity and facilitating its passage through cell membrane. The resulting conjugate can then be excreted, effectively achieving detoxification. This study systematically explored the in vitro reaction between GSH and DON, examining various factors influencing their coupling efficiency and the toxicity of the resulting products. It also highlighted the potential of glutathione S-transferase (GST) as a novel and effective approach for DON detoxification, underscoring its catalytic role in this process. These findings are of paramount importance for developing innovative strategies to mitigate DON contamination in grains and their processed products, thereby contributing to enhanced food safety.

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