Study on the effects and molecular mechanisms of arsenic-induced kidney damage in mice

Arsenic, a common environmental contaminant, presents a significant risk of severe health issues after prolonged or high-dose exposure. Although arsenic-induced nephrotoxicity is well-known, the specific molecular mechanisms are not yet fully understood. To explore the dose-dependent toxic effects and mechanisms of sodium arsenite (NaAsO₂) on the kidney, C57BL/6 mice were intraperitoneally injected with NaAsO₂ at doses of 0, 3, 6, and 12 mg/kg every other day for 28 days. Our results showed that, compared to the control, the 6 mg/kg group had a notably reduced rate of body weight gain and lower levels of crucial antioxidant enzymes, including catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (Gpx). Conversely, the 12 mg/kg group exhibited significantly higher serum levels of creatinine (CREA) and uric acid (UA), increased Gpx activity, and a greater rate of kidney cell apoptosis. RNA-sequencing (RNA-seq) analysis revealed 6 differentially expressed genes (DEGs) in the 3 mg/kg group (4 upregulated, 2 downregulated), 33 DEGs in the 6 mg/kg group (15 up, 18 down), and 29 DEGs in the 12 mg/kg group (12 up, 17 down). Functional enrichment analysis using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways suggested that disruption of cellular development and metabolic balance could be underlying arsenic-induced kidney damage. Among the DEGs, Early Growth Response 1 (Egr1) was consistently expressed across all three dose groups. Immunofluorescence (IF) assays further confirmed that Egr1 protein expression was significantly increased in the 12 mg/kg group, with a notable portion of the protein moving into the nucleus. Overall, these findings suggest that arsenic exposure causes kidney injury by inducing oxidative stress and cell death. We propose that Egr1, through its nuclear translocation and regulation of apoptotic and oxidative pathways, acts as a key mediator in this harmful process.