Molecular Hydrogen Protects Human Melanocytes from Oxidative Stress by Activating Nrf2 Signaling

Oxidative stress is proven to be critical for the initiation and progression of vitiligo. Molecular hydrogen (H-2) possesses potent antioxidant activity and has been shown to protect against various oxidative stresserelated diseases. In this study, we first investigated the effects and mechanisms of H-2 in human melanocytes damaged by hydrogen peroxide. We initially found that H-2 reduced intracellular ROS accumulation and malondialdehyde levels in both vitiligo specimens and hydrogen peroxideetreated melanocytes in vitro in a concentration- and time-dependent manner, concomitant with the enhancement of antioxidant enzyme activity. Correspondingly, H-2 reversed hydrogen peroxideeinduced apoptosis and dysfunction in both normal and vitiligo melanocytes. H-2 protected mitochondrial morphology and function in melanocytes under stress and promoted the activation of Nrf2 signaling, whereas Nrf2 deficiency abolished the protective effect of H-2 against hydrogen peroxideeinduced oxidative damage. Furthermore, H-2 positively modulated beta-catenin in hydrogen peroxideetreated melanocytes, and the beta-catenin pathway was implicated in H-2-induced Nrf2 activation. Collectively, our results indicate that H-2 could be a promising therapeutic agent for vitiligo treatment via attenuating oxidative damage, and its beneficial effect in human melanocytes might involve Wnt/beta-cateninemediated activation of Nrf2 signaling.