Lutein Modulates Stress-Responsive Signaling Pathways in THLE-2 Human Hepatocytes Under Intestinal Failure-Associated...

Intestinal dysfunction and parenteral nutrition (PN) can trigger a spectrum of liver disorders collectively referred to as intestinal failure-associated liver disease (IFALD), for which therapeutic options remain limited. In the present study, we investigated the modulatory effects of the bioactive xanthophyll carotenoid lutein in an in vitro IFALD model utilizing human THLE-2 hepatocytes exposed to lipopolysaccharide and Intralipid to mimic PN-associated inflammatory and metabolic stress. Because lutein is poorly water-soluble and patients receiving PN lack enteral intake of this compound, we also evaluated the cyto- and hemocompatibility of a human serum albumin-based lutein nanoformulation developed to enable intravenous administration. A bead-based multiplex immunoassay revealed that lutein attenuated dysregulation of inflammatory and metabolic signaling by modulating total and phosphorylated levels of MAPKs, NF-κB, Akt, STAT5, CREB, and p70S6K. Lutein also affected lipid metabolism-related gene expression, decreasing SREBF2 and restoring ABCA1 and PRKAA2 mRNA toward control levels, as determined by qPCR. Nanoformulated lutein, with a mean particle size of approximately 160 nm, was non-toxic in THLE-2 cells and exhibited hemocompatibility in a human erythrocyte hemolysis assay. Together, our findings provide both biological and technological rationale for further exploration of lutein-based strategies to mitigate IFALD in patients receiving PN.