Perfluoroundecanoic Acid Inhibits Liver Cell Development in Pubertal Male Rats via Inducing Oxidative Stress

Perfluoroundecanoic acid (PFUnA) is a long-chain perfluoroalkyl substance. However, whether PFUnA affects liver development during puberty is still unclear. Male 35-day-old Sprague-Dawley rats were gavaged with 0 (corn oil), 1, 5, and 10 mg/kg/day of PFUnA for 21 days. Liver weight was remarkably increased by PFUnA at ≥1 mg/kg, while serum alanine aminotransferase levels were higher at 5 and 10 mg/kg. PFUnA upregulated the expression of <i>Lxrα, Hmgcr, Srebp2</i>, and <i>Cyp7a1</i> and downregulated the expression of <i>Abcg8, Ldlr, Sod1</i>, and <i>Cat</i>. These changes were also confirmed at the protein level. It increased the release of inflammatory factors (IL-1β, IL-6, and TNF-α). It also downregulated the fibrosis-related gene expression of <i>Adamts6</i> and <i>Col4a1</i>. Similar results were obtained in HepG2 cells treated with 50 μM PFUnA in vitro. PFUnA induced oxidative stress and perturbed lipid metabolism. Overall, PFUnA may induce oxidative stress and disrupt lipid metabolism to have an inhibitory influence on pubertal liver development.