Network toxicological analysis of sodium dehydroacetate in food safety
Jing Jin, Xue Yan, Liang Tian
Abstract
Sodium dehydroacetate (Na-DHA), a synthetic preservative under tightened regulations, was evaluated for multi-organ toxicity using network toxicology. ADMETlab3.0 predicted genotoxicity, hepatotoxicity, and carcinogenicity risks. Target mining identified 13 cancer-related, 11 liver injury-related, and 8 genotoxicity-related core genes, with shared hubs (ALOX5, PTGS2, SMAD3, TNF) across pathologies. Functional analyses revealed inflammation, oxidative stress, and immune dysregulation as central mechanisms. KEGG pathway analysis linked cancer/liver injury to AGE-RAGE signaling (TNF, NOX4) and genotoxicity to efferocytosis impairment (PTGS2, ALOX5), suggesting DNA repair disruption. The integrated network demonstrated Na-DHA's pleiotropic effects through convergent pathways, transcending organ-specific toxicity. This systemic profile challenges conventional single-endpoint assessments, advocating comprehensive multi-organ risk evaluation.