Microarray analysis of the mechanism of liver injury induced by acute cadmium exposure in rats

Abstract

Objective To explore the mechanism of acute cadmium (Cd) exposure-induced liver injury in rats. Methods Sixteen male SD rats were randomly divided into control group and acute cadmium exposure group (n=8), and received a single peritoneal injection of normal saline and 1.25 mg/kg CdCl2 dissolved in normal saline, respectively. The rats were euthanized at 24 h after the injection for histopathological assessment using HE staining and detection of serum alanine transaminase (ALT) and aspartate transaminase (AST) activities using a biochemical analyzer. The tissue microarray GSE65198 dataset from the GEO database was analyzed for the gene expression profiles in the liver tissues of rats receiving identical treatments, and online analysis with GEO2R was performed to compare the data between the control and daily 1.25 mg/kg cadmium exposure group to identify the differentially expressed genes (DEGs). The functions and pathway enrichment of the DEGs were analyzed using Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The hub genes were identified by protein-protein interactions (PPIs) network and Cytoscape software, and their expression levels in the liver tissues of the rats were verified by qRT-PCR. Results Compared with the control rats, the rats with acute Cd exposure showed marked elevations of serum AST and ALT levels (P < 0.01) without exhibiting obvious pathologies in the liver tissues, where no ballooning hepatocyte degeneration, focal necrosis or inflammatory cell infiltration was found. GO and KEGG enrichment analysis confirmed that the DEGs were highly enriched in cell cycle arrest (the Top 1 signaling pathway). Cdc20, Ccnb1, Cdk1, Top2a, and Ube2c were the hub genes in the PPI network of the DEGs, all of which showed decreased expression at the mRNA level in the liver of rats with acute Cd exposure (P < 0.01). Only Cdk1 out of the 3 hub genes involved in cell cycle (Cdc20, Ccnb1, and Cdk1) was significantly down-regulated following cadmium exposure in rats (P < 0.05). Conclusion Acute Cd exposure induces liver injuries in rats by causing cell cycle arrest of the hepatocytes, and Cdk1, along with other hub genes, may play important roles in Cd-induced cell cycle arrest.

Keywords

• cdcl2
• rats
• hepatoxicity
• microarray
• cell cycle