699 The histone deacetylase inhibitor vorinostat protects melanocytes from H2O2-induced oxidative stress and inflammatory response via Nrf2 pathway

Abstract

Vitiligo is a common skin depigmenting disorder characterized by the loss of functional melanocytes. Oxidative stress plays a critical role in the pathogenesis of vitiligo, and antioxidant therapy is a promising therapeutic strategy to prevent or even reverse the progression of depigmentation. Histone deacetylase inhibitors (HDACi) have emerged as a potential therapeutic strategy for oxidative damage and inflammatory diseases. The present investigation evaluates the protective effects of Vorinostat, a common HDACi, on melanocytes and further investigates the mechanism involved. In the present study, we first found that Vorinostat protected melanocytes against H2O2-induced apoptosis and alleviated the excessive accumulation of reactive oxygen species (ROS) and the lipid peroxidation by enhancing the activity of several antioxidative enzymes. Furthermore, we demonstrated that the antioxidative effects of Vorinostat were achieved by activating Nrf2 and its downstream antioxidative genes. In addition, the treatment with Vorinostat decreased the expressions of proinflammatory cytokines including IL-1β and IL-6 induced by H2O2 and interfering Nrf2 with siRNA disrupted the protective effect. In conclusion, our study demonstrates that vorinostat protects melanocytes from oxidative stress-induced cell death and inflammatory response via Nrf2 pathway.