Ustiloxins is a mycotoxin produced by the metabolism of Rice false smut. Studies have shown that Ustiloxins may be toxic to animals, but there is still a lack of toxicological evidence. The liver, as the main organ for the biotransformation of foreign chemicals, may be the direct target organ of Ustiloxins toxicity. In this study, we found that cell viability decreased in a dose- and time-dependent manner when BNL CL.2 cells were treated with different concentrations of Ustiloxins (0, 5, 10, 20, 30, 40, 60, 80, 100, 150 and 200 μg/mL) for 24 and 48 h. In addition, scanning electron microscope observation showed that the cell membrane of the experimental group was damaged, with the appearance of apoptotic bodies. Moreover, the ROS and GSH levels were significantly increased in cells exposed to Ustiloxins. We analyzed the key action targets of Ustiloxins on hepatocyte injury using full-length transcriptomics. A total of 1099 differentially expressed genes were screened, of which 473 genes were up-regulated, and 626 genes were down-regulated. Besides, we also found that the expression of MCM7 and CDC45 in BNL CL.2 cells treated with Ustiloxins decreased, and the expression of CCl-2, CYP1b1, CYP4f13, and GSTM1 increased according to qRT-PCR. Ustiloxins might change CYP450 and GST-related genes, affect DNA replication and cell cycle, and lead to oxidative stress and liver cell injury.

乌霉毒素是稻曲病代谢产生的一种霉菌毒素。研究表明Ustiloxins可能对动物有毒，但目前仍缺乏毒理学证据。肝脏作为外来化学物质生物转化的主要器官，可能是乌司洛菌素毒性的直接靶器官。在这项研究中，我们发现当BNL CL.2细胞用不同浓度的Ustiloxins（0、5、10、20、30、40、60、80、100）处理时，细胞活力以剂量和时间依赖性方式下降。 、150 和 200 μg/mL) 24 和 48 小时。另外，扫描电镜观察显示，实验组细胞膜受损，出现凋亡小体。此外，暴露于Ustiloxins的细胞中ROS和GSH水平显着增加。我们使用全长转录组学分析了 Ustiloxins 对肝细胞损伤的关键作用靶点。共筛选出差异表达基因1099个，其中上调基因473个，下调基因626个。此外，qRT-PCR还发现，用Ustiloxins处理的BNL CL.2细胞中MCM7和CDC45的表达下降，而CCl-2、CYP1b1、CYP4f13和GSTM1的表达增加。 Ustiloxins 可能会改变 CYP450 和 GST 相关基因，影响 DNA 复制和细胞周期，并导致氧化应激和肝细胞损伤。