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首页> 美国卫生研究院文献>Toxins >Biotransformation of the Mycotoxin Zearalenone to its Metabolites Hydrolyzed Zearalenone (HZEN) and Decarboxylated Hydrolyzed Zearalenone (DHZEN) Diminishes its Estrogenicity In Vitro and In Vivo
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Biotransformation of the Mycotoxin Zearalenone to its Metabolites Hydrolyzed Zearalenone (HZEN) and Decarboxylated Hydrolyzed Zearalenone (DHZEN) Diminishes its Estrogenicity In Vitro and In Vivo

机译：霉菌毒素玉米赤霉烯酮对其代谢产物水解玉米赤霉烯酮（HZEN）和脱羧水解玉米赤霉烯酮（DHZEN）的生物转化降低了其体内和体内的雌激素性。

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Zearalenone (ZEN)-degrading enzymes are a promising strategy to counteract the negative effects of this mycotoxin in livestock. The reaction products of such enzymes need to be thoroughly characterized before technological application as a feed additive can be envisaged. Here, we evaluated the estrogenic activity of the metabolites hydrolyzed zearalenone (HZEN) and decarboxylated hydrolyzed zearalenone (DHZEN) formed by hydrolysis of ZEN by the zearalenone-lactonase Zhd101p. ZEN, HZEN, and DHZEN were tested in two in vitro models, the MCF-7 cell proliferation assay (0.01–500 nM) and an estrogen-sensitive yeast bioassay (1–10,000 nM). In addition, we compared the impact of dietary ZEN (4.58 mg/kg) and equimolar dietary concentrations of HZEN and DHZEN on reproductive tract morphology as well as uterine mRNA and microRNA expression in female piglets (n = 6, four weeks exposure). While ZEN increased cell proliferation and reporter gene transcription, neither HZEN nor DHZEN elicited an estrogenic response, suggesting that these metabolites are at least 50–10,000 times less estrogenic than ZEN in vitro. In piglets, HZEN and DHZEN did not increase vulva size or uterus weight. Moreover, RNA transcripts altered upon ZEN treatment (EBAG9, miR-135a-5p, miR-187-3p and miR-204-5p) were unaffected by HZEN and DHZEN. Our study shows that both metabolites exhibit markedly reduced estrogenicity in vitro and in vivo, and thus provides an important basis for further evaluation of ZEN-degrading enzymes.
机译：玉米赤霉烯酮（ZEN）降解酶是一种有前景的策略，可以抵消这种霉菌毒素对家畜的负面影响。这种酶的反应产物需要在技术应用中作为饲料添加剂被彻底表征之前。在这里，我们评估了由玉米赤霉烯酮-内酰胺酶Zhd101p水解ZEN形成的代谢产物水解玉米赤霉烯酮（HZEN）和脱羧水解玉米赤霉烯酮（DHZEN）的雌激素活性。 ZEN，HZEN和DHZEN在两个体外模型中进行了测试：MCF-7细胞增殖测定（0.01–500 nM）和雌激素敏感性酵母生物测定（1–10,000 nM）。此外，我们比较了日粮ZEN（4.58 mg / kg）和等摩尔日粮中HZEN和DHZEN对雌性仔猪的生殖道形态以及子宫mRNA和microRNA表达的影响（n = 6，接触4周）。尽管ZEN增加了细胞增殖和报告基因的转录，但HZEN和DHZEN均未引发雌激素反应，这表明这些代谢产物在体外的雌激素水平至少比ZEN低50–10,000倍。在仔猪中，HZEN和DHZEN不会增加外阴大小或子宫重量。此外，ZEN处理后改变的RNA转录本（EBAG9，miR-135a-5p，miR-187-3p和miR-204-5p）不受HZEN和DHZEN的影响。我们的研究表明，两种代谢物在体内和体外均表现出明显降低的雌激素性，因此为进一步评估ZEN降解酶提供了重要依据。

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