Alternariol is a mycotoxin produced by Alternaria spp. relevant to the food safety area due to its abundance in certain foods. The shortage of data on its toxicology, also as a part of chemical mixtures, prevents setting regulation to limit its abundance in food. To extend knowledge on the possible mechanisms underpinning alternariol toxicology in chemical mixtures, this work assessed the effects of urolithin C, a structurally related gut ellagitannin-derived metabolite, on its absorption and phase II metabolism in a monolayer of Caco-2 cells. A computational study was also used to provide a mechanistic explanation for the results obtained. Urolithin C influenced transport and phase II metabolism of alternariol with a late reduction of transport to the basolateral compartment. Moreover, it caused an early effect in terms of accumulation of alternariol glucuronides in the basolateral compartment, followed by a late reduction of glucuronides in both compartments. Concerning alternariol sulfates, the data collected pointed to a possible competition of urolithin C for the sulfotransferases resulting in a reduced production of alternariol sulfates. Our results provide a compelling line-of-evidence pointing to the need to systematically tackle the evaluation of mycotoxin toxicity in the context of chemical mixture.

中文翻译：

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与结构相关的肠道微生物代谢物尿石素 C 相结合，对霉菌毒素交链菌素的转运和 II 期代谢的体外研究

Alternariol 是一种由 Alternaria spp 产生的真菌毒素。由于其在某些食物中含量丰富，因此与食品安全领域相关。其毒理学数据的短缺，也作为化学混合物的一部分，阻碍了制定法规来限制其在食物中的丰度。为了进一步了解支持化学混合物中交链孢菌素毒理学的可能机制，这项工作评估了尿石素 C（一种结构相关的肠道鞣花单宁衍生代谢物）对其在 Caco-2 细胞单层中的吸收和 II 期代谢的影响。还使用计算研究为获得的结果提供机械解释。尿石素 C 影响了交链孢素的转运和 II 期代谢，晚期转运到基底外侧室的减少。而且，它在基底外侧隔室中的交链孢葡糖苷酸积累方面产生了早期影响，随后在两个隔室中葡萄糖醛酸苷的后期减少。关于硫酸交链孢，收集到的数据表明尿石素 C 可能与磺基转移酶竞争，导致交链孢硫酸盐的产生减少。我们的结果提供了令人信服的证据线，表明需要系统地处理化学混合物背景下的霉菌毒素毒性评估。