Ketoconazole alleviates UVB-induced photoaging by suppressing ROS generation and mitochondrial dysfunction in dermal fibroblasts and ex vivo porcine skin models

Background: Ultraviolet (UV) radiation is a major contributor to skin damage and photoaging, primarily through the generation of reactive oxygen species (ROS), which disrupt cellular functions and degrade extracellular matrix. Demand for effective agents to counteract these effects is increasing. Objective: This study investigated the protective effects of ketoconazole (KCZ), a well-known antifungal agent, against UVB-induced photoaging using human dermal fibroblasts (Hs68) and an ex vivo porcine skin model. Methods: Hs68 cells and ex vivo porcine skin were exposed to UVB radiation and subsequently treated with KCZ. We assessed cell viability, collagen production, MMP-1 expression, ROS levels, mitochondrial function, and the activation of the MAPK-AP-1 signaling pathway. Results: KCZ alleviated UVB-induced reductions in cell viability, suppressed MMP-1 expression, and prevented collagen degradation in Hs68 cells. In the ex vivo porcine skin model, KCZ reduced UVB-induced skin damage and collagen breakdown. Additionally, KCZ significantly inhibited UVB-induced ROS generation and rescued mitochondrial dysfunction, as evidenced by recovery of mitochondrial membrane potential and respiratory capacity. KCZ also blocked activation of the UV-stimulated MAPK-AP-1 signaling pathway. Conclusion: KCZ exhibits significant anti-photoaging effects by reducing UV-induced oxidative stress, preserving mitochondrial function, and preventing degradation of the extracellular matrix. These findings suggest that KCZ may be a potential anti-photoaging agent.