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 (H₂) possesses potent antioxidant activity and has been shown to protect against various oxidative stress-related diseases. In this study, we first investigated the effects and mechanisms of H₂ in human melanocytes damaged by hydrogen peroxide. We initially found that H₂ reduced intracellular ROS accumulation and malondialdehyde levels in both vitiligo specimens and hydrogen peroxide-treated melanocytes in vitro in a concentration- and time-dependent manner, concomitant with the enhancement of antioxidant enzyme activity. Correspondingly, H₂ reversed hydrogen peroxide-induced apoptosis and dysfunction in both normal and vitiligo melanocytes. H₂ protected mitochondrial morphology and function in melanocytes under stress and promoted the activation of Nrf2 signaling, whereas Nrf2 deficiency abolished the protective effect of H₂ against hydrogen peroxide-induced oxidative damage. Furthermore, H₂ positively modulated β-catenin in hydrogen peroxide-treated melanocytes, and the β-catenin pathway was implicated in H₂-induced Nrf2 activation. Collectively, our results indicate that H₂ could be a promising therapeutic agent for vitiligo treatment via attenuating oxidative damage, and its beneficial effect in human melanocytes might involve Wnt/β-catenin-mediated activation of Nrf2 signaling.