Ameliorative Effects of Vitamin E and Lutein on Hydrogen Peroxide-Triggered Oxidative Cytotoxicity via Combined Transcriptome and Metabolome Analysis

Vitamin E and lutein both belong to food functional factors, which have cytoprotective potential and antioxidant effects. However, mechanism details at cell level remain scarce. In this study, HepG2 cells were utilized to inquire and compare the ameliorative effects of vitamin E and lutein under H₂O₂-induced oxidative stress through a combined transcriptomic and metabolomic profiling, in addition to physiology and biochemistry determination. Cell cytotoxicity caused by H₂O₂ was ameliorated by vitamin E or lutein as evidenced by elevating cell viability and balancing the redox system. Vitamin E had greater efficacy on ameliorating oxidative cytotoxicity than lutein. Transcriptome data revealed that differentially expressed genes were mainly enriched in the transport-related, enzyme-related, and oxidative stress-related GO terms with vitamin E pretreatment. Extracellular organization-related, biological process-related, and apoptosis-related GO terms were meaningfully enriched with lutein pretreatment. Metabolome data showed that with vitamin E ameliorative effects, the disturbed metabolic pathways included thiamine metabolism, vitamin digestion and absorption, and ABC transporters. With lutein ameliorative effects, KEGG pathway analysis showed enrichment of amino sugar and nucleotide sugar metabolism, pyrimidine metabolism, and starch and sucrose metabolism. Collectively, our study provides essential insights into utilization of vitamin E and lutein as a potential supplement for effective therapy of disease associated with oxidative stress.