Ácido betulínico aplicado sobre a pele de camundongos com lesões psoriasiformes induzidas por imiquimode: efeitos locais, biossinalização e efeitos potencialmente adversos

• Autor(a) principal: Fernandes, Flávia de Souza
• Data de Publicação: 2020
• Tipo de documento: Tese
• Idioma: por
• Título da fonte: Repositório Universitário da Ânima (RUNA)
• Texto Completo: https://repositorio.animaeducacao.com.br/handle/ANIMA/15185
• topic: Ácido betulínico; Lesões psoriasiformes; Tratamento sobre a pele; Eficácia e segurança; Mecanismo de ação

Introduction: Psoriatic patients discontinue oral or injectable treatments alleging efficacy and safety problems. Betulinic acid (AB) forms supramolecular aggregates by spontaneous self-assembly in a hydroalcoholic vehicle, which can potentially be deposited on psoriasiform lesions of the animals' skin from which it could be released, having a systemic reach and exhibiting a broad spectrum of assets, including for cases moderate and severe psoriasis. The aim of this study was to evaluate the efficacy, safety and mechanism of action of AB applied on the skin of mice with psoriasiform lesions induced by imiquimod. Methodology: Every 24 h (5 days), imiquimod was applied to the shaved back of the mice (except in the untreated group); 2 h later, the vehicle (10% aqueous glycerol solution) (100 µL), 0.05 mg / ml clobetasol or 0.5 mg / ml AB ​​were administered by the same route. The severity index by area of ​​psoriasis (PASI), body weight, water / feed consumption and walking (n = 12 / group) were evaluated. The time for complete cleaning of the skin (CSC) was evaluated (n = 6 / group) and AB caused its greatest reduction (up to 40%). In six other mice / group, the skin was quantified: epidermal acanthosis and the number of lymphocytes and granulocytes in the dermal papillae. In addition, phosphorylation of Akt and ERK. In the blood, TNF, IL-17A, IFNγ, IL-10, TGFβ and toxicity indicators were evaluated. Results: AB and clobetasol reduced PASI (p <0.001) and acanthosis (up to 3 times), normalizing immunocyte infiltration and TNF concentration, reducing IL-17A (≅ 50%) (both, p = 0.01 ), p-Akt (p <0.01 and 0.05, respectively) and p-ERK2 (p <0.001 and 0.05, respectively). Only AB normalized the INFγ concentration and was the only one capable of inhibiting p-ERK1 (p <0.001), without intensifying the toxicity of imiquimod. Conclusion: The data suggest that AB can be considered a candidate molecule for the development of a new treatment for psoriasis applied to the skin.