Ultraviolet A (UVA) radiation has been identified as a significant factor contributing to skin photoaging and skin diseases, operating through the excessive generation of reactive oxygen species (ROS) and the subsequent induction of DNA damage. Plant-derived antioxidants have demonstrated efficacy in mitigating UVA-induced damage; nevertheless, their instability limits their therapeutic potential. This study investigates the mechanisms of antioxidant and cytoprotective effects of squalane (Sq), a stable, plant-derived triterpene, in human dermal fibroblasts (HDFs) exposed to UVA radiation. Sq was administered at concentrations ranging from 0.005% to 0.015% prior to UVA exposure (10 J/cm2). It has been found that Sq counteracted UVA-induced ROS formation, decreased the level of reduced thiol groups, activated apoptosis, and inhibited DNA biosynthesis. Immunofluorescence analysis revealed that Sq suppressed the UVA-induced expression of p53, caspase-3, caspase-9, and PARP, while restoring the activity of the pro-survival p-Akt/mTOR pathway. The findings indicate that Sq exerts protective effects on UVA-induced fibroblast damage through a combination of antioxidant and anti-apoptotic mechanisms.
Keywords: DNA damage; ROS; UVA radiation; apoptosis; oxidative stress; squalane.