EFFECTS OF METFORMIN ON OXIDATIVE DAMAGE AND INFLAMMATORY RESPONSE CAUSED BY ULTRAVIOLET B RADIACION (UVB) IN HUMAN KERATINOCYTES

SOUZA NETO, F; FRIEDRICH, A; PAZ, M; LOURENÇO CECCHINI, A; LEONI, J; GONZALEZ MAGLIO, D

Congreso; IV LASID Meeting; LXIII Argentinean Immunology Society Meeting; II French-Argentinean Immunology Meeting; 2015

Ultraviolet radiation (UVr) induces aninflammatory and oxidative response in epidermal exposed cells, due to mitochondrialand cytosolic alterations. Both responses are related to skin cancerdevelopment. Themitochondrial electron transport chain (one of the major cellular generators ofROS) is inhibited by Metformin, an oral anti-hyperglycemic agent derived from Galegaofficinalis, which also has anticancereffects, which are explained trough the activation of AMPK. Theaim of this work was to evaluate the effects of Metformin on UV-inducedinflammation and mitochondrial alterations.HaCaT cell line pre-treated with 1 mM Metformin ormedia were exposed to 25 mJ/cm2 of UVr and incubated for 24 hs withor without 1 mM Metformin (a total of 4 groups). Non irradiated treated cellswere used as control. Mitochondrial membrane depolarization, superoxide (O2·-)and cytokine production were evaluated by flow cytometry and ELISA, respectively.Metformin was more effectivewhen solely administered before irradiation compared to the othertreatments.  It increased metabolicallyactive cells (21.5% vs. 12.4%) and decreased O2·-producing cells (56% vs. 76%) as well as it reduced IL-6 production (2390 vs 3233pg/ml) compared to non-treated irradiated cells. No changes in IL-10 productionwere detected. Metformin treatment after irradiation was less effective inreducing UV-induced damage. All differences were statistically significant (p<0.05).Metformin is capable of modulating UV-inducedinflammation and mitochondrial alterations in keratinocytes. The presentedresults set Metformin as a possible preventive agent against UV-induceddamaged. Further studies are necessary to accurately prove and understand Metformin anticancer effects.