Pirfenidone Protects from UVB-Induced Photodamage in Hairless Mice

Background: Ultraviolet radiation (UV) is the main environmental factor that causes histological degenerative changes of the skin giving rise to a chronic process called photodamage. Non-melanoma skin cancer induced by UVB radiation is a result of a cascade of molecular events caused by DNA damage in epidermis cells, including persistent inflammation, oxidative stress, and suppression of T cell-mediated immunity. Retinoids such as tretinoin have been widely used in skin to treat photoaging and photodamage, though its secondary adverse effects have been recognized. Pirfenidone (PFD) has emerged as an antifibrogenic, anti-inflammatory and antioxidant agent, and in this work its efficacy was evaluated in a model of UVB-induced photodamage. Methods: Epidermal, dermal, and inflammatory changes were measured by histomorphometric parameters. In addition, gene, and protein expression of key molecules in these processes were evaluated. Results: Our results revealed an anti-photodamage effect of topical PFD with absence of inflammatory skin lesions determined by dermoscopy. In addition, PFD reduced elastosis, improved organization, arrangement, and deposition of dermal collagens, downregulated several pro-inflammatory markers such as NF-kB, IL-1, IL-6 and TNFa, and decreased keratinocyte damage. Conclusion: Topical pirfenidone represents a promising agent for the treatment of cell photodamage in humans. Clinical trials need to be carried out to explore this premise.

Automated summary

Ultraviolet radiation (UV) is the main cause of skin photodamage, which leads to histological degenerative changes and non-melanoma skin cancer. Retinoids have been commonly used to treat photoaging, but their adverse effects are recognized. Pirfenidone (PFD) has shown anti-inflammatory, antifibrogenic, and antioxidant properties. In this study, topical PFD was found to effectively reduce photodamage and inflammation in a UVB-induced model, making it a promising treatment for cell photodamage in humans. Clinical trials are needed to further investigate its potential.