Microbial biotransformation of Zearalenone (ZEN) is a promising deactivation approach. The residual toxicity and stability of Zearalenone-14-phosphate (ZEN-14-P) and Zearalenone-16-phosphate (ZEN-16-P), two novel microbial phosphorylation products of ZEN, remain unknown. We investigated the cytotoxicity, oxidative stress, proinflammatory, and estrogenic activity of phosphorylated ZENs using porcine intestinal cells, uterine explants, and human endometrial cells and traced their metabolic fate by liquid chromatography-tandem mass spectrometry (LC-MS)/MS analysis. The phosphorylated ZENs significantly decreased the viability of the IPEC-J2 and Ishikawa cells. Similar to ZEN, phosphorylation products induced significant oxidative stress, activated the expression of proinflammatory cytokines, and demonstrated estrogenic activity through upregulation of estrogen-responsive genes, activation of alkaline phosphatase, and proliferation of endometrial glands. LC-MS/MS analysis pointed out that although phosphorylated ZENs are partially hydrolyzed to ZEN, their respective metabolic pathways differ. We conclude that phosphorylation might not be sufficient to detoxify ZEN, leaving its cytotoxic, proinflammatory, and estrogenic properties intact.

中文翻译：

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玉米赤霉烯酮的磷酸化保持其毒性


玉米赤霉烯酮 （ZEN） 的微生物生物转化是一种很有前途的失活方法。ZEN 的两种新型微生物磷酸化产物 Zearalenone-14-phosphate （ZEN-14-P） 和 Zearalenone-16-phosphate （ZEN-16-P） 的残留毒性和稳定性仍然未知。我们使用猪肠细胞、子宫外植体和人子宫内膜细胞研究了磷酸化 ZENs 的细胞毒性、氧化应激、促炎和雌激素活性，并通过液相色谱-串联质谱 （LC-MS）/MS 分析追踪它们的代谢归宿。磷酸化的 ZEN 显著降低了 IPEC-J2 和 Ishikawa 细胞的活力。与 ZEN 类似，磷酸化产物诱导显着的氧化应激，激活促炎细胞因子的表达，并通过上调雌激素反应基因、激活碱性磷酸酶和子宫内膜腺体增殖来表现出雌激素活性。LC-MS/MS 分析指出，尽管磷酸化的 ZENs 部分水解为 ZEN，但它们各自的代谢途径不同。我们得出结论，磷酸化可能不足以使 ZEN 解毒，使其细胞毒性、促炎性和雌激素特性完好无损。