RXRα agonist bexarotene attenuates radiation-induced skin injury by relieving oxidative stress

Objective To investigate the protective effect of bexarotene in radiation-induced skin injury and elucidate underlying mechanism. Methods Irradiated cellular and animal models were established using an X-ray linear accelerator. Cell viability and apoptosis were evaluated by CCK8 and flow cytometry. In vivo protective effect of bexarotene was measured in irradiated SD rats. The antioxidant capacity of bexarotene was validated by DCF-DA method. The signaling pathways involved in bexarotene-mediated skin repair were enriched by RNA sequencing. Results Bexarotene could significantly restore the proliferation and inhibit the apoptosis of WS1 cells with radiation damage (P ​< ​0.05). Moreover, bexarotene could effectively shorten the process of skin damage and promote skin repair in a rat model of radiation-induced skin injury (P ​< ​0.05). Mechanistically, bexarotene effectively reduced the expression of RXRα (P ​< ​0.05), thus leading to an early decrease in reactive oxygen species (ROS) after radiation exposure. Furthermore, a transcriptome analysis indicated that bexarotene-mediated recovery of radiation damage involves redox signaling, immune regulation, lipid metabolism and autophagy. Conclusion Bexarotene is a promising therapeutic agent in the treatment of radiation-induced skin injury.