Full-length transcriptomics study of Ustiloxins-induced hepatocyte injury

Abstract

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.

Keywords: CYP450; DNA replication; Full-length transcriptomics; Hepatocyte injury; Ustiloxins.