Application of HepG2-derived organoid and organ-on-a-chip platforms in elucidating selenium-mediated protection against cadmium-induced liver dysfunction.

HepG2 cells were cultured into liver organoids (more native liver-like than 2D cultures) and integrated into a microfluidic chip, which regulates flow, nutrients, and waste to simulate in vivo hepatic microcirculation. Key findings: Cadmium (Cd) exposure shows a positive dose-response with liver damage; 40 ng/mL selenium (Se) alleviates 3 sets of liver biochemical dysfunctions under 40 μg/mL Cd co-exposure, but 160/640 ng/mL Se diminishes this protection. Metabolomics (40 μg/mL Cd vs. 640 ng/mL Se+Cd) identified two mechanisms: high Se induces oxidative stress and disrupts liver cellular metabolism. This study provides data/theory for rational Se use against Cd-induced liver dysfunction. The platform integrates organoid/organ-on-a-chip assessments with microfluidic metabolomics (a cross-scale toxicological system) and informs 3D cell model development.