Combined effects of arsenic and palmitic acid on oxidative stress and lipid metabolism disorder in human hepatoma HepG2 cells

Abstract

The toxicity of arsenic (As) can be influenced by many nutrients in food. However, the combined effects and underlying mechanisms of As and palmitic acid (PA) are still unclear. Here, cell viability, oxidative stress, lipids accumulation, gene expression profiles, and metabolome profiles of human hepatoma HepG2 cells exposed to As, PA, and As + PA were analyzed and compared. Results showed that co-exposure of 100 μM PA and 2 μM As induced lower cell viability, higher intracellular reactive oxygen species level, more lipid droplet accumulation, and more intracellular triglyceride contents than As alone or PA alone exposure. High-throughput quantitative PCR and 1H NMR-based metabolomics analysis showed that co-exposure of As and PA caused all toxic effects on gene expression and metabolome profiles induced by As alone or PA alone exposure, and showed higher toxicities. Gene expression profiles in the As + PA group had higher similarity with those in the As group than the PA group. However, PA played a more important role in metabolism disorder than As in their interactive effects. Oxidative stress and lipid metabolism disorder were found to be the main toxic effects in the As + PA group. Several differentially expressed genes (such as OXR1, OXSR1, INSR, and PPARA) and changed metabolites (such as pyruvate, acetate, and L-phenylalanine) were involved in the combined toxicity of As and PA. This study provides basic information on the interactive effects of As and PA, which is useful for the health risk assessment of As and FFA.