2-Fluorofucose Attenuates Hydrogen Peroxide-Induced Oxidative Stress in HepG2 Cells via Nrf2/keap1 and NF-κB Signaling Pathways.

Fucosylation is one of the most important glycan terminal modifications that affects multiple biological activities of proteins. 2-Fluorofucose (2FF), its specific inhibitor, has recently been reported to reveal numerous biological effects by blocking fucosylation both in vitro and in vivo. The current study aimed to evaluate the effect of 2FF on hydrogen peroxide (HO)-induced oxidative damage in vitro. In our study, treatment with HO increased the level of fucosylation, and 2FF improved the cell viability in HO-treated HepG2 cells. Our study also showed that 2FF significantly decreased the overproduction of reactive oxygen species (ROS) induced by HO and the activities of catalase, glutathione and Mn-superoxide dismutase were remarkably increased by 2FF pretreatment. Furthermore, 2FF attenuated HO-induced early mitochondria dysfunction. The second part of the study revealed that 2FF enhanced antioxidant capacity by affecting Nrf2/keap1 and NF-κB signaling pathways in HepG2 cells. Being pretreated with 2FF significantly increased the nuclear translocation of Nrf2 and simultaneously promoted the expression of downstream proteins, such as HO-1 and NQO1. Moreover, 2FF remarkably suppressed the expression of inflammation-associated proteins. Taken together, these data suggest that 2FF might have a potential therapeutic effect for oxidative stress.