Toxics, Vol. 13, Pages 483: An Integrated Approach Involving Metabolomics and Transcriptomics Reveals Arsenic-Induced Toxicity in Human Renal Cells

Toxics doi: 10.3390/toxics13060483

Authors:
Lin Rong
Xinxin Liang
Xingfang Zhang
Yajun Qiao
Guoqiang Li
Yuancan Xiao
Hongtao Bi
Lixin Wei

Accumulating epidemiological evidence has indicated that arsenic exposure can lead to kidney injury. However, the underlying mechanisms of arsenic-induced nephrotoxicity have not been fully elucidated. In this study, the effect of sodium arsenite on the cell viability of HEK-293 cells was studied using a CCK-8 assay. Metabolomic and transcriptomic analyses were applied to identify differential metabolites (DMs) and differentially expressed genes (DEGs) in human renal cells exposed to arsenite, respectively. The results showed that the IC50 of arsenite on HEK-293 cells was 25 μM. A total of 621 DMs were identified in arsenic-treated cells (VIP > 1, p < 0.05). The results of the metabolome analysis revealed that purine metabolism was the major affected pathway, with 21 DMs enriched within this pathway. Additionally, 9831 DEGs were obtained after arsenic exposure (|log2FC| > 1, Padj < 0.05). The results of the transcriptome analysis showed that ECM–receptor interaction and cell adhesion molecules were the major altered KEGG pathways, with 54 and 70 enriched DEGs, respectively. Integrated metabolomics and transcriptomics analyses revealed that the predominant mechanisms underlying arsenic-induced nephrotoxicity were associated with the perturbations of lipid metabolism and purine metabolism. Overall, the present study provided comprehensive insights into the metabolic and transcriptional alterations in human renal cells in response to arsenic exposure, providing a referable scientific basis for subsequent arsenic-induced nephrotoxicity studies.

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