Cadmium causes hepatopathy by changing the status of DNA methylation in the metabolic pathway

Toxicity caused by the heavy metal Cadmium leads to liver diseases; this finding has generated interest among researchers. We detected DNA methylation using Whole Genome Bisulfite Sequencing (WGBS) to study the relationship between Cadmium exposure and liver damage. Forty-eight Sprague-Dawley rats were randomly divided into six groups, and given normal saline or 2.5, 5, 10, 20, and 40 mg/kg body weight per day CdCl₂ by gavage. Twelve weeks later, their liver tissues were collected for pathological examination and DNA extraction. Increased exposure to Cadmium led to a reduction in the amount of weight gain as well as pathological degeneration and necrosis of liver cells of the rats. Using WGBS, we found that DNA methylation changes in the high-dose exposure group were more remarkable, and most of the changes occurred in the gene promoter region. GO enrichment analysis showed that the genes were enriched in the biological process of "response to stimulus." KEGG analysis revealed that metabolic pathways, like MAPK, PI3K-Akt and cAMP, had the largest number of enriched genes. Using Integrative Genomics Viewer (IGV), the demethylation of F2rl3 after Cadmium poisoning was established. This finding may explain why there are changes in liver metabolism after Cadmium poisoning.