Vitiligo is a common depigmented disorder characterized by a loss of functional melanocytes and melanin from epidermis based on various hypotheses, the consensus has been reached that it is a result of complex interactions between oxidative stress and autoimmunity processes in patients with vulnerable genetic background.
The melanocytes of vitiligo, according to genome-wide association studies, acquire high susceptibility to damage or apoptosis under certain circumstances and final destruction resulted from the synergistical interactions between reactive oxygen species (ROS) and autoimmunity. Specifically, both the abnormal generation of epidermal ROS and the compromised antioxidant defences indicate the loss of cellular redox equilibrium contributes to vitiligo. The crucial role of autoimmunity in melanocyte destruction is supported by the markedly increased incidence of vitiligo in cases of immune dysfunction. However, the specific interactions between ROS and autoimmunity in vitiligo still remains unclear. Here, by summarizing our current understanding, we try to shed light on ROS’s role in the induction of autoimmune responses and melanocyte destruction. The excessive production of ROS in vitiligo the excessive ROS are caused by overproduction and inadequate antioxidants defences. Various exogenous and endogenous stimuli involved in the aetiopathogenesis of vitiligo are reported to be responsible for the overproduction of ROS, including ultraviolet (UV) irradiation, trauma, stress, major infection, malignancies, neural abnormalities, vaccination, pregnancy, calcium imbalance, certain drugs, hormones, and exposure to cytotoxic compounds. However, for the shortage of evidence, the initiation of excessive ROS production in vitiligo still remains obstreat. Mitochondrial dysfunction is doubted to be one of culprits. The membrane lipid defects of mitochondria, such as the altered transmembrane distribution of cardiolipin and cholesterol, was found to be responsible for the generation of ROS in peripheral blood mononuclear cells of vitiligo patients. These stimuli, in our supposition, may indirectly induce ROS overproduction through impairing mitochondria in their distinctive pathways. ROS comprise a family of oxygen-based free radicals, including superoxide anions, hydroxyl radicals, hydrogen peroxide (H2O2), and singlet oxygen, which are produced during multiple cellular processes, such as cellular metabolism, proliferation, differentiation, apoptosis, and immune reactions. Pollution, atmospheric gases, ionizing or UV radiation, microorganisms, viruses, and xenobiotics/drugs are proven environmental elicitors of excessive ROS that quickly prevail against tissue antioxidants and other oxidant-degrading pathways.
Meanwhile, melanocytes tend to own increased vulnerability to oxidative stress due to the reduction of catalase and glutathione peroxidase activity. The gene polymorphisms of CAT, which are conventionally thought to be associated with vitiligo susceptibility, still lack sufficient evidence to support its pathogenicity according to a latest metaanalysis.