Eugenol-Derived Cytoprotective Action Against Dityrosine-Induced Oxidative Stress in Mice Liver via Akt/Nrf2/ARE...

Dityrosine (Dityr), a byproduct of protein oxidation in protein-rich food, induces oxidative stress, inflammation, and apoptosis, jeopardizing human health. Eugenol (EUG), a natural compound with antioxidative and anti-inflammatory properties, was investigated for its protective effects against Dityr-induced hepatotoxicity in this work. In this study, in vivo and in vitro analyses demonstrated EUG's protective effects against Dityr-induced hepatotoxicity. EUG significantly attenuated oxidative stress markers, inflammatory infiltration, fibrotic progression, and apoptotic signaling in mice liver tissues. Mechanistically, EUG activated the Akt/NF-E2-related factor 2/antioxidant response element (Akt/Nrf2/ARE) pathway, enhancing cellular antioxidant capacity while suppressing pro-inflammatory cytokine release. In HepG2 cells, EUG treatment effectively counteracted Dityr-induced ROS overproduction and cell death through Nrf2-mediated antioxidant upregulation. In conclusion, our findings indicate that EUG effectively mitigates Dityr-induced oxidative stress via the Akt/Nrf2/ARE pathway, and this antioxidative impact further inhibits inflammation and apoptosis. These effects ultimately ameliorate liver function impairment caused by Dityr.