Simvastatin Protects Human Melanocytes from H2O2-Induced Oxidative Stress by Activating Nrf2

Abstract

The prevention of hydrogen peroxide (HO)-induced oxidative stress has proved to be beneficial to vitiligo patients. Simvastatin possesses antioxidative capacity and has shown protective effect in various oxidative stress-related diseases. However, whether simvastatin can protect human melanocytes against oxidative stress has not been investigated. In this study, we initially found that pretreatment with 0.1 μmol/L to 1.0 μmol/L simvastatin led to increased cell viability and decreased cell apoptosis of melanocytes in response to HO. In addition, simvastatin was able to potentiate the activity of antioxidant enzymes and lessen intracellular reactive oxygen species accumulation. Furthermore, we found that simvastatin promoted the activation of nuclear erythroid 2-related factor (Nrf2) and that knockdown of Nrf2 abolished the protective effect of simvastatin against HO-induced oxidative damage. More importantly, the mutual enhancement between mitogen-activated protein kinase pathways and p62 contributed to simvastatin-induced Nrf2 activation in melanocytes. Finally, simvastatin showed more antioxidative capacity and better protective effect than aspirin in HO-treated melanocytes. Taken together, our results show that simvastatin protects human melanocytes from HO-induced oxidative stress by activating Nrf2, thus supporting simvastatin as a potential therapeutic agent for vitiligo.

Geniposide prevents H2 O2 -induced oxidative damage in melanocytes by activating the PI3K-Akt signalling pathway

“…Extremely high levels of H 2 O 2 have been observed in vitiligo epidermis, and these are responsible for melanocyte loss . ROS accumulation directly induces melanocyte damage and causes an autoimmune response that subsequently results in melanocyte destruction …”

“…However, the underlying mechanisms are not fully understood, although oxidative stress is one possible pathogenic event . The accumulation of reactive oxygen species (ROS), mainly consisting of H 2 O 2 , superoxide anions and hydroxyl radicals, in melanocytes induces apoptosis and might therefore be involved in melanocyte destruction . Consequently, the application of antioxidants to ameliorate oxidative damage might represent a potential therapeutic approach for the treatment of vitiligo.…”

Reactive Oxygen Species in Skin Repair, Regeneration, Aging, and Inflammation

“…The effects of atorvastatin and simvastatin on oxidative stress markers in rats with hyperhomocysteinemia (Hhcy) were analyzed, and simvastatin was shown to have a superior antioxidant activity compared with that of the atorvastatin, independent of its effects on the lipid profile, but dependent on the homocysteine concentration. Simvastatin was shown to protect human melanocytes from H 2 O 2 -induced oxidative stress by activating NRF2, which indicates that this compound may be used for vitiligo treatment [83]. Sufficiently powered prospective clinical and intervention studies are required to determine the antioxidant effectiveness of simvastatin [84].…”

Simvastatin Protects Dopaminergic Neurons Against MPP+-Induced Oxidative Stress and Regulates the Endogenous Anti-Oxidant System Through ERK

“…In a related study, we observed that the anti-oxidative stress function of Sim in dopaminergic neurons is very prominent. Previous evidence suggests that Sim is able to activate Nrf2 and respond positively to oxidative stress caused by H 2 O 2 [10]. We have determined the anti-oxidant properties of Sim.…”