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

J Invest Dermatol. 2020 Nov;140(11):2230-2241.e9. doi: 10.1016/j.jid.2019.03.1165. Epub 2020 Mar 29.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Humans
  • Hydrogen / pharmacology*
  • Hydrogen Peroxide / pharmacology
  • Keratinocytes / drug effects
  • Melanocytes / drug effects*
  • Melanocytes / metabolism
  • NF-E2-Related Factor 2 / physiology*
  • Oxidative Stress / drug effects*
  • Signal Transduction / physiology
  • Vitiligo / drug therapy
  • Wnt Signaling Pathway / physiology
  • beta Catenin / physiology


  • CTNNB1 protein, human
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • beta Catenin
  • Hydrogen
  • Hydrogen Peroxide