Efeito dos ácidos oleico e linoleico no modelo ex vivo de pele humana psoriásica: avaliação do estresse oxidativo

Abstract

Psoriasis is a chronic, incurable inflammatory disease that affects approximately 3% of the global population and may lead to significant systemic complications. Despite advances in research, the underlying mechanisms of its pathogenesis—such as oxidative stress—remain poorly understood. This study investigated the role of oxidative stress in an ex vivo model of human psoriatic skin induced by imiquimod (IMQ), as well as the potential therapeutic effects of linoleic acid (LNA) and oleic acid (OA). Healthy human skin samples were maintained in culture medium and topically treated with a cream containing 5% IMQ or a neutral cream base, while simultaneously receiving LNA, OA, or vehicle (V) diluted in the culture medium. An in vitro model using immortalized human keratinocytes treated with IMQ and LNA was also employed to support the ex vivo findings. The psoriatic phenotype was characterized by histological analysis and immune profiling, with a focus on interleukins IL-17 and IL-23. Oxidative stress was assessed through measurements of oxidants, oxidation products, antioxidant levels, GSH/GSSG ratio, and enzymatic activity. IMQ treatment led to increased epidermal thickness and keratinocyte hyperproliferation, accompanied by elevated levels of IL-17 and IL-23, defining a characteristic psoriatic inflammatory profile. Additionally, a pronounced redox imbalance was observed, marked by decreased GSH levels and catalase activity, increased MDA levels, and exacerbated activation of the NF-κB p65 pathway. While OA had no significant effect on these parameters, LNA mitigated inflammation, oxidative imbalance, and IMQ-induced morphological alterations. This study contributed to the characterization of a functional ex vivo model of human psoriasis that effectively reproduces the histological, inflammatory, and redox features of the disease. In addition to reinforcing the contribution of oxidative stress to psoriasis pathogenesis, the findings highlight LNA as a potential adjuvant therapeutic agent with anti-inflammatory and antioxidant properties.