Unveiling the Hub Genes Associated with Manganese-Induced Hepatotoxicity

Abstract Excessive exposure to manganese (Mn) can cause severe toxicity in human and animal organs, particularly the liver. However, the specific mechanisms of Mn-induced hepatotoxicity remain unclear. Thus, the objective of this study was to identify the key genes associated with hepatotoxicity caused by Mn administration. We obtained the gene expression data set GSE59923 from the Gene Expression Omnibus, which included liver samples treated with manganese chloride (MnCl 2 ) as well as control samples. Through our analysis, we identified 222, 351, and 494 differentially expressed genes (DEGs) in the livers treated with MnCl 2 at 700 mg/kg on the 1st, 3rd, and 5th day, respectively. Notably, we found a total of 27 overlapping DEGs in the liver samples. Biological process analysis revealed that these common DEGs were associated with the response to xenobiotic stimulus, cellular calcium ion homeostasis, and ion transmembrane transport. Pathway analysis further indicated the involvement of cAMP, p53, PI3K-Akt, MAPK, and AMPK signaling pathways in Mn-induced hepatotoxicity. Furthermore, we identified several important genes, including CCR2 , CDKN1A , CELSR2 , LCN2 , and PER2 , which appeared to play a role in Mn-induced hepatotoxicity. Taken together, this study sheds light on the molecular mechanisms underlying Mn-induced hepatotoxicity, contributing to our overall understanding of this condition.