The effects and mechanisms of sodium arsenite exposure on liver injury in mice

As a common environmental pollutant, chronic exposure to arsenic can cause liver damage, however the molecular mechanisms remain unclear. This study investigates explore the liver toxicity induced by NaAsO₂ exposure in mice, focusing on molecular mechanisms and potential therapeutic targets. Male C57BL/6 J mice were treated with NaAsO₂ at 3, 6, and 12 mg/kg doses for 4 weeks. Body weight, liver index, serum ALT/AST levels, oxidative stress markers (MDA, SOD, GPx), histopathological changes, and apoptotic were assessed. RNA sequencing was used to identified differentially expressed genes (DEGs) and protein-protein interaction (PPI) network was further established to elucidate the interactions among the potential targets. Significant liver damage was observed at 6 mg/kg and 12 mg/kg doses, with the 12 mg/kg group showing elevated serum ALT (39.34 ± 1.21 U/L) and AST (200.79 ± 9.73 U/L). At those doses, oxidative stress markers were significantly altered and histology revealed hepatocyte disarrangement, vacuolation, and necrosis, and the TUNEL assay further conformed significant apoptosis. In the livers of treated mice, transcriptomic analysis identified 149 DEGs at 6 mg/kg and 259 DEGs at 12 mg/kg. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated disruptions in circadian rhythm, lipid metabolism, and immune signaling pathways. More importantly, Il1b, Acta2, and Serpine1 were identified as key regulatory genes, showing elevated expression. In conclusion, these findings indicate that NaAsO₂ exposure disrupts metabolic, circadian, and immune pathways, with inflammation being exacerbated at higher doses. Il1b, Acta2, and Serpine1 emerge as promising therapeutic targets for arsenic-induced liver damage. Future research should focus on long-term interventions and drug repurposing strategies to validate these targets and mitigate arsenic toxicity.