Toxicogenomic analysis of physiologically important metals: An integrated in silico approach.

Abstract

Biologically important metals regulate cellular homeostasis in living systems. Anthropogenic exposure to these metals can cause adverse effects, including an increased incidence of diseases in humans such as cancer, lung, and cardiovascular defects. However, the effects of metals and the common genes/signaling pathways involved in metal toxicity have not been elucidated. Hence, the present study used toxicogenomic data mining with the comparative toxicogenomics database to explore the impact of these metals. The metals were categorized into transition, alkali, and alkaline earth. The common genes were identified and subjected to functional enrichment analysis. Further, gene-gene and protein-protein interactions were assessed. Also, the top ten transcription factors and miRNAs that regulate the genes were identified. The phenotypes and diseases that have increased incidence upon alterations of these genes were detected. Overall, we were able to identify IL1B and SOD2 as the common genes, along with the AGE-RAGE signaling pathway in diabetic complications as the common pathway altered. Enriched genes and pathways specific to each metal category were also found. Further, we identified heart failure as the major disease that could have increase in the incidence upon these metals' exposure. In conclusion, exposure to essential metals might cause adverse effects via inflammation and oxidative stress.