Metformin inhibits the inflammatory and oxidative stress response induced by skin UVB-irradiation and provides 4-hydroxy-2-nonenal and nitrotyrosine formation and p53 protein activation

Abstract

Skin exposure to ultraviolet B (UVB) radiation leads to local oxidative stress, inflammation, systemic immunosuppression and, ultimately, the development of skin cancer. Metformin is the most prescribed drug for type 2 diabetes, and it has been shown that chronic treatments with this drug reduces skin cancer incidence.Objective. Our aim was to analyze the effects of metformin on UVB-induced acute local damage.Methods. C57/BL6 mice were pretreated with 90 mg/kg of metformin for 11 days and exposed to 400 mJ/cm2 of UVB radiation. Twenty-four hours later, we obtained skin samples to determine oxidative stress and the inflammatory response. Results. We observed that metformin did not prevent UVB-induced epidermal damage, Langerhans cells loss or mitochondrial alterations in epidermal cells. However, it improved the reducing state in the skin, increasing antioxidant molecules that led to reduced 4-hidroxynonenal and nitrotyrosine labeling. Local inflammatory mediators increased by UVB radiation, such as IL-6 and IL-1β, were also reduced by metformin.Conclusion. We demonstrated that metformin reduces UVB-induced local and systemic damage, changes that could explain its antitumoral effect. Thus, the use of metformin as a potential agent to maintain skin homeostasis and prevent UVB-induced lesions requires evaluation.