Crudo Francesco, Partsch Vanessa, Braga Dennis, Blažević Ruzica, Rollinger Judith M, Varga Elisabeth, Marko Doris
Department of Food Chemistry and Toxicology, Faculty of Chemistry, University of Vienna, Währinger Str. 38, 1090, Vienna, Austria.
Doctoral School in Chemistry, Faculty of Chemistry, University of Vienna, Vienna, Austria.
Arch Toxicol. 2025 Jan;99(1):407-421. doi: 10.1007/s00204-024-03877-1. Epub 2024 Oct 2.
Alternaria mycotoxins may pose significant challenges to food safety and public health due to the wide spectrum of reported adverse effects. Despite this, critical information on the immunomodulatory and antiestrogenic properties of most of these contaminants is still lacking. The present study aimed to identify the mycotoxins responsible for the immunosuppressive and antiestrogenic effects of a complex extract of Alternaria mycotoxins (CE) obtained by growing an Alternaria alternata strain on rice. Through a toxicity-guided fractionation procedure involving the production of CE-fractions by supercritical fluid chromatography and mycotoxin quantification by LC-MS/MS, the mycotoxins alternariol (AOH), tenuazonic acid (TeA), altertoxin I (ATX-I), and alterperylenol (ALTP) were identified as potential toxicologically relevant constituents contributing to the in vitro effects exerted by the extract. The assessment of the immunomodulatory effects, performed by applying the NF-κB reporter gene assay in THP1-Lucia™ monocytes, revealed the scarce contribution of AOH to the effects exerted by the CE. TeA showed no effect on the NF-κB pathway up to 250 µM, whereas ATX-I and ALTP suppressed the LPS-mediated pathway activation at concentrations ≥ 1 µM. The evaluation of antiestrogenic effects, performed in Ishikawa cells by applying the alkaline phosphatase assay, revealed the ability of ALTP (≥ 0.4 µM) and ATX-I (≥ 2 µM) to suppress the estrogen-dependent expression of enzyme activity. Given the risk of detrimental impacts stemming from alterations in endocrine and systemic immune responses by the investigated mycotoxins, further studies are needed to elucidate their underlying mechanisms of action and comprehensively evaluate the health risks posed by these toxins.
链格孢霉菌毒素可能对食品安全和公众健康构成重大挑战，因为有大量关于其不良反应的报道。尽管如此，关于这些污染物中大多数的免疫调节和抗雌激素特性的关键信息仍然缺乏。本研究旨在确定由链格孢菌株在大米上生长获得的链格孢霉菌毒素复合提取物（CE）的免疫抑制和抗雌激素作用所涉及的霉菌毒素。通过毒性导向分级分离程序，包括用超临界流体色谱法制备CE级分以及用LC-MS/MS进行霉菌毒素定量，确定了交替链格孢酚（AOH）、细交链孢菌酮酸（TeA）、变应毒素I（ATX-I）和变链格孢菌素（ALTP）为可能与毒理学相关的成分，它们对提取物产生的体外效应有贡献。通过在THP1-Lucia™单核细胞中应用NF-κB报告基因检测对免疫调节作用进行评估，结果显示AOH对CE产生的效应贡献不大。TeA在浓度高达250µM时对NF-κB途径无影响，而ATX-I和ALTP在浓度≥1µM时抑制LPS介导的途径激活。通过在石川细胞中应用碱性磷酸酶检测对抗雌激素作用进行评估，结果显示ALTP（≥0.4µM）和ATX-I（≥2µM）能够抑制雌激素依赖性酶活性表达。鉴于所研究的霉菌毒素可能因内分泌和全身免疫反应改变而产生有害影响，需要进一步研究以阐明其潜在作用机制，并全面评估这些毒素所带来的健康风险。
