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调控和新兴霉菌毒素对 SH-SY5Y 细胞活力和线粒体功能的单一和联合作用。

Single and combined effects of regulated and emerging mycotoxins on viability and mitochondrial function of SH-SY5Y cells.

机构信息

Departamento de Farmacología, Facultad de Veterinaria, Universidad de Santiago de Compostela, Lugo, 27002, Spain.

Departamento de Farmacología, Facultad de Veterinaria, Universidad de Santiago de Compostela, Lugo, 27002, Spain.

出版信息

Food Chem Toxicol. 2021 Aug;154:112308. doi: 10.1016/j.fct.2021.112308. Epub 2021 May 29.

Abstract

Co-occurrence of emerging and regulated mycotoxins in contaminated samples has been widely documented, but studies about their combined toxicity are scarce. In this report, the regulated mycotoxins deoxynivalenol, fumonisin B1 and zearalenone, and the emerging ones enniatin A, enniatin B and beauvericin were tested in SH-SY5Y human neuroblastoma cells. Their individual and binary combined effects on cell viability and mitochondrial function were evaluated. The results with individual mycotoxins revealed that deoxynivalenol and emerging mycotoxins were the most damaging to neuronal cells, presenting IC values between 0.35 and 2.4 μM. Interestingly, non-regulated mycotoxins triggered apoptosis by affecting to mitochondrial membrane potential. However, when regulated and non-regulated mycotoxins were binary mixed, antagonistic effects were found in all cases. Finally, cow feed and milk extracts were analysed by UHPLC-MS/MS, detecting the presence of several mycotoxins included in this study. These extracts were tested in neuroblastoma cells, and damaging effects on cell viability were found. Although binary combinations of mycotoxins produced antagonistic effects, their mixture in natural matrixes induces greater effects than expected. Therefore, it would be interesting to explore the matrix influence on mycotoxin toxicity, and to continue studying the neurotoxic mechanism of action of emerging mycotoxins, as they could be a health hazard.

摘要

已广泛记录了污染样本中新兴和受管制霉菌毒素的共同出现,但关于它们联合毒性的研究却很少。在本报告中,受管制霉菌毒素脱氧雪腐镰刀菌烯醇、伏马菌素 B1 和玉米赤霉烯酮,以及新兴霉菌毒素恩镰菌素 A、恩镰菌素 B 和 beauvericin,在人神经母细胞瘤 SH-SY5Y 细胞中进行了测试。评估了它们对细胞活力和线粒体功能的单独和二元联合作用。单独使用霉菌毒素的结果表明,脱氧雪腐镰刀菌烯醇和新兴霉菌毒素对神经元细胞的损害最大,IC 值在 0.35 和 2.4 μM 之间。有趣的是,非管制霉菌毒素通过影响线粒体膜电位引发细胞凋亡。然而,当受管制和非管制霉菌毒素混合时,在所有情况下都发现了拮抗作用。最后,通过 UHPLC-MS/MS 分析了牛饲料和牛奶提取物,检测到了本研究中包含的几种霉菌毒素的存在。这些提取物在神经母细胞瘤细胞中进行了测试,发现它们对细胞活力有损害作用。尽管霉菌毒素的二元组合产生了拮抗作用,但它们在天然基质中的混合物会产生比预期更大的影响。因此,探索基质对霉菌毒素毒性的影响,并继续研究新兴霉菌毒素的神经毒性作用机制将是很有趣的,因为它们可能对健康构成危害。

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