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

Abstract

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 stresserelated 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 peroxideetreated melanocytes in vitro in a concentration- and time-dependent manner, concomitant with the enhancement of antioxidant enzyme ac- tivity. Correspondingly, H2 reversed hydrogen peroxideeinduced 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 peroxideeinduced oxidative damage. Furthermore, H2 positively modulated b-catenin in hydrogen peroxideetreated melanocytes, and the b-catenin pathway was implicated in H2-induced Nrf2 acti- vation. 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/b-cateninemediated activation of Nrf2 signaling.

Study details

Article type

Original Research

Disease / injury model

Vitiligo (oxidative stress-induced melanocyte damage)

Dose comparison

The study compared the effects of different concentrations (2%, 35%, 75%) and durations (2-24 hours) of H2 exposure on oxidative stress and cell viability, showing a concentration- and time-dependent protective effect.

Dose-dependent effect

Yes

Outcome

Positive

Findings

Molecular hydrogen (H2) protects human melanocytes from oxidative stress by reducing ROS and MDA, enhancing antioxidant enzyme activity, preserving mitochondrial function, and activating Nrf2 signaling. The protective effect is concentration- and time-dependent, and is abolished by Nrf2 deficiency. H2 also modulates b-catenin, implicating the Wnt/b-catenin pathway in Nrf2 activation. H2 shows promise as a therapeutic agent for vitiligo.