Laboratory for Advanced Lipid Analysis, Faculty of Health Sciences, Hokkaido University, Kita 12, Nishi 5, Sapporo, Japan.
Food Control Department, Faculty of Veterinary Medicine, Zagazig University, Zagazig, 44519, Egypt.
Mycotoxin Res. 2020 Aug;36(3):287-299. doi: 10.1007/s12550-020-00392-x. Epub 2020 Feb 19.
Deoxynivalenol (DON) is a type B trichothecenes that is widely contaminating human and animal foods, leading to several toxicological implications if ingested. Induction of oxidative stress and production of lipid peroxides were suggested to be the reasons for DON-induced cytotoxicity. However, detailed and comprehensive profiling of DON-related lipid hydroperoxides was not identified. Furthermore, the mechanisms behind DON-induced cytotoxicity and oxidative stress have received less attention. Zinc (Zn) is an essential element that has antioxidant activities; however, the protective effects of Zn against DON-induced adverse effects were not examined. Therefore, this study was undertaken to investigate DON-induced cytotoxicity and oxidative damage to human HepG2 cell lines. Furthermore, a quantitative estimation for the formed lipid hydroperoxides was conducted using LC-MS/MS. In addition, DON-induced transcriptomic changes on the inflammatory markers and antioxidant enzymes were quantitatively examined using qPCR. The protective effects of Zn against DON-induced cytotoxicity and oxidative stress, the formation of lipid hydroperoxides (LPOOH), and antioxidant status in HepG2 cells were investigated. Finally, the effects of DON and Zn on the Nrf2-Keap1 pathway were further explored. The achieved results indicated that DON caused significant cytotoxicity in HepG2 cells accompanied by significant oxidative damage and induction of the inflammatory markers. Identification of DON-related LPOOH revealed the formation of 22 LPOOH species including 14 phosphatidylcholine hydroperoxides, 5 triacylglycerol hydroperoxides, and 3 cholesteryl ester hydroperoxides. DON caused significant downregulation of Nrf2-regulated antioxidant enzymes. Zn administration led to significant protection of HepG2 cells against DON-induced adverse effects, probably via activation of the Nrf2-Keap1 pathway.
脱氧雪腐镰刀菌烯醇（DON）是一种 B 型单端孢霉烯族毒素，广泛污染人类和动物食品，如果摄入，会产生几种毒理学影响。氧化应激的诱导和脂质过氧化物的产生被认为是 DON 诱导细胞毒性的原因。然而，尚未确定与 DON 相关的脂质氢过氧化物的详细和全面分析。此外，DON 诱导的细胞毒性和氧化应激的机制受到的关注较少。锌（Zn）是一种必需元素，具有抗氧化活性；然而，Zn 对 DON 诱导的不良反应的保护作用尚未得到检验。因此，本研究旨在研究 DON 对人 HepG2 细胞系的细胞毒性和氧化损伤作用。此外，还使用 LC-MS/MS 对形成的脂质氢过氧化物进行定量估计。此外，还使用 qPCR 定量检查 DON 诱导的炎症标志物和抗氧化酶的转录组变化。研究了 Zn 对 DON 诱导的细胞毒性和氧化应激、脂质氢过氧化物（LPOOH）的形成以及 HepG2 细胞中的抗氧化状态的保护作用。最后，进一步探讨了 DON 和 Zn 对 Nrf2-Keap1 通路的影响。研究结果表明，DON 导致 HepG2 细胞显著的细胞毒性，同时伴有显著的氧化损伤和炎症标志物的诱导。鉴定 DON 相关的 LPOOH 揭示了 22 种 LPOOH 物质的形成，包括 14 种磷脂氢过氧化物、5 种三酰基甘油氢过氧化物和 3 种胆固醇酯氢过氧化物。DON 导致 Nrf2 调节的抗氧化酶显著下调。Zn 给药导致 HepG2 细胞对 DON 诱导的不良反应有显著的保护作用，可能是通过激活 Nrf2-Keap1 通路。
