Metformin effect on driving cell survival pathway through inhibition of UVB-induced ROS formation in human keratinocytes.

Human skin functions go beyond serving only as a mechanical barrier. As a complex organ, the skin is capable to cope with external stressors cutaneous by neuroendocrine systems to control homeostasis. However, constant skin exposure to ultraviolet (UV) radiation causes progressive damage to cellular skin constituents, mainly due excessive reactive oxygen species (ROS) production. The present study shows new approaches of metformin (MET) as an antioxidant agent. Currently, MET is the first line treatment of type 2 diabetes and has attracted attention, based on its broad mechanism of action. Therefore, we evaluated MET antioxidant potential in cell-free systems and in UVB irradiated human keratinocyte HaCaT cells. In cell-free system assays MET did not show intrinsic scavenging activity on DPPH radicals or superoxide (O2-) xanthine/luminol/xanthine oxidase-generated. Cell-based results demonstrated that MET was able to reduce UVB-induced intracellular ROS and NADPH oxidase-dependent superoxide (O2-) production. MET posttreatment of HaCaT cells reduced ERK 1/2 phosphorylation, NADPH oxidase activity, and cell death by apoptosis. These findings suggest that the protection mechanism of MET may be through the inhibition of ROS formation enzyme. These results showed that MET might be a promising antioxidant agent against UV radiation induced skin damage.