In vitro study reveals α-tocopherol metabolites protect hepatocytes against oxidative stress via HO-1 upregulation, highlighting indirect gene-mediated antioxidant defense.
Key Points
To evaluate the antioxidant and cytoprotective activities of α-tocopherol metabolites, αCEHC and αCMBHC, compared to parent α-tocopherol in liver cells.
Mouse hepatoma Hepa1c1c7 cells were pretreated with α-tocopherol (αT) and its metabolites (αCEHC and αCMBHC) prior to hydrogen peroxide-induced oxidative challenge.
Radical scavenging was measured via hydrogen peroxide and DPPH assays, while mechanism of action was evaluated through antioxidant-related gene expression and HO-1 inhibitor co-treatment.
Pretreatment with αT, αCEHC, and αCMBHC provided cytoprotection against hydrogen peroxide toxicity and scavenged DPPH radicals, despite exhibiting minimal direct hydrogen peroxide scavenging.
Compounds significantly upregulated heme oxygenase-1 (HO-1) expression likely via Nrf2 transcription factor activation, and pharmacological inhibition of HO-1 abolished this protective effect.