Immune dysregulation and cellular dysfunction mediate di-n-pentyl phthalate-induced hepatotoxicity: Insights from...

Phthalates are plastic-derived endocrine-disrupting chemicals that can migrate into the environment and enter the human body, posing considerable health risks. Di-n-pentyl phthalate (DNPP), a commonly used phthalate, has not been fully characterized with respect to its hepatotoxic effects. In this study, we investigated DNPP-induced liver toxicity and its underlying mechanisms in mice using single-cell RNA sequencing (scRNA-seq). A DNPP-exposed mouse model was established, followed by histological evaluation of liver tissues and measurement of serum transaminase levels. Additionally, scRNA-seq, flow cytometry, and quantitative real-time polymerase chain reaction were performed to assess the changes in cellular subpopulations and gene expression profiles. DNPP exposure substantially increased liver-to-body weight ratio and serum alanine aminotransferase levels in a dose-dependent manner. Histological analysis revealed enhanced lymphocyte infiltration in DNPP-exposed livers. ScRNA-seq analysis demonstrated marked alterations in T-NK, myeloid, and endothelial cells, accompanied by the downregulation of the expressions of genes associated with immune cell chemotaxis, myeloid cell stress response, and endothelial protein synthesis. These findings suggest that DNPP may induce liver injury by disrupting immune homeostasis and impairing cellular functions. Overall, this study provides novel insights into DNPP-induced hepatotoxicity and highlights the need for strengthened monitoring of DNPP in environmental media to safeguard public health.