To explore how dimethyl fumarate (DMF) protects against oxidative stress-induced melanocyte injury, in order to offer new ideas for vitiligo treatment.

The optimal DMF concentration for melanocytes was determined by assessing its impact on their proliferation. An oxidative stress model was created using H₂O₂. The study involved four groups: normal control, H₂O₂-treated, H₂O₂+DMF, and H₂O₂+DMF+ML385 (a Nrf2 inhibitor). Melanocyte morphology, dendrite length, and cell number were observed. The effect of DMF on melanocyte apoptosis under oxidative stress was evaluated with an apoptosis detection kit. Flow cytometry and immunofluorescence staining were used to measure intracellular ROS levels and CAT/SOD activity. Western blot analysis was performed to detect the expression of Nrf2, p-Nrf2, and HO-1. The four groups were compared for the above parameters to confirm Nrf2's role in DMF's antioxidant mechanism.

The H₂O₂-treated group had shorter dendrites, fewer dendrites, more apoptosis-positive cells, higher intracellular ROS, and lower SOD/CAT activity than the normal control group. The H₂O₂+DMF group had significantly inhibited oxidative stress-induced melanocyte apoptosis, reduced ROS, increased SOD/CAT activity, and boosted Nrf2, p-Nrf2, and HO-1 expression. In the H₂O₂+DMF+ML385 group, SOD/CAT activity decreased, and intracellular ROS rose compared to the H₂O₂+DMF group.

DMF protects against oxidative stress-induced melanocyte injury by activating the Nrf2/HO-1 pathway and enhancing antioxidant capacity, showing potential for vitiligo therapy.