Department of Food and Drug, University of Parma, Via G.P. Usberti 27/A, 43124 Parma, Italy.
Department of Food Chemistry and Toxicology, Faculty of Chemistry, University of Vienna, Waehringer Str. 38, 1090 Vienna, Austria.
Food Chem. 2018 May 15;248:253-261. doi: 10.1016/j.foodchem.2017.12.013. Epub 2017 Dec 7.
Xenoestrogenic mycotoxins may contaminate food and feed posing a public health issue. Besides the zearalenone group, the Alternaria toxin alternariol (AOH) has been described as a potential mycoestrogen. However, the estrogenicity of Alternaria toxins is still largely overlooked and further data are needed to better describe the group toxicity. In the frame of risk assessment, mixed in silico/in vitro approaches already proved to be effective first-line analytical tools. An integrated in silico/in vitro approach was used to investigate the effects of metabolic and chemical modifications on the estrogenicity of AOH. Among the considered modifications, methylation was found critical for enhancing estrogenicity (as seen for alternariol monomethyl ether (AME)) while hydroxylation and glucuronidation had the opposite effect (as seen for 4-hydroxy AOH and 4-hydroxy AME). The structure-activity relationship analysis provided the structural rationale. Our results provide insights to design more efficient risk assessment studies expanding knowledge over the group toxicity.
外源性雌激素真菌毒素可能会污染食物和饲料，从而对公共健康造成威胁。除了玉米赤霉烯酮外，链格孢菌毒素 alternariol（AOH）也被认为是一种潜在的真菌雌激素。然而，链格孢菌毒素的雌激素活性仍在很大程度上被忽视，需要进一步的数据来更好地描述该组毒素的毒性。在风险评估框架内，基于计算机的体外混合方法已被证明是有效的一线分析工具。本研究采用了一种整合的基于计算机的体外方法来研究代谢和化学修饰对 AOH 雌激素活性的影响。在所考虑的修饰中，甲基化被发现对增强雌激素活性至关重要（如 alternariol monomethyl ether (AME) 所见），而羟基化和葡萄糖醛酸化则产生相反的效果（如 4-羟基 AOH 和 4-羟基 AME 所见）。结构-活性关系分析提供了结构上的基本原理。我们的研究结果为设计更有效的风险评估研究提供了见解，扩展了对该组毒性的认识。
