Nanoeugenol modula o efeito pró-inflamatório da oxazolona em modelo de dermatite de contato alérgica aguda e crônica em camundongos

• Ano de defesa: 2022
• Autor(a) principal: Araujo, Emmanuel Vinicius Oliveira
• Orientador(a): Leal, Luzia Kalyne Almeida Moreira
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Palavras-chave em Português: Eugenol; Nanotecnologia; Dermatite Alérgica de Contato
• Link de acesso: http://www.repositorio.ufc.br/handle/riufc/67811

The allergic contact dermatitis (ACD) is classified as skin inflammatory disease provoked by cutaneous exposition to allergenic substances, capable to sensitize the genetically predisposed individuos and consequently further a specific response to new exposition. The actual pharmacotherapy shows considerable eficace, however, it has disadvantages associated with the drug safety, justifying the importance to search new medicine. Previous studies performed by our research group, aimed to avaliad the eugenol nanoencapsulation impact (NEUG) to treatment the irritative contact dermatitis, showing importance results in terms to cytotoxicity decrease in keratinocyte and potentiation topical anti-inflammatory effect. The aim of the present study was to contribute to the development of a topical nanodrug, NEUG, evaluating the anti-inflammatory properties in murine experimental models of allergic contact dermatitis oxazolone-induced. Swiss mices were sensitized and desafied with oxazolone 1,5 and 0,5%, respectively. The treatments were realized with NEUG (0,16 - 0,08 and 0,04 mg/ear) by topical route. Initially, it was evaluated the NEUG antiedematogenyc effect and myeloperoxidase activity in acute inflammatory site oxazolone-induced through a single application, to determine the better therapeutic dose. The 0,16 mg/ear dose was selected and pró-inflammatory (TNF-α, IL-1β, IFN-γ, IL-4) and anti-inflammatory (IL-10) cytokines levels were investigated. Topical NEUG (0,16 mg/ear) reduced by 75% the ear oedema compared to the oxazolone group, as well as the leukocyte accumulation, measured by myeloperoxidase activity, decreased by 37%. In addition, NEUG showed module capacity the inflammatory response through the reduction pró-inflammatory cytokines teciduals levels, as TNF-α, IFN-γ, IL-1β, IL-4, by 43,2%, 74,8%, 45,8%, and 47,8%, respectively, and increased by 49% the IL-10 production in inflamed tissue. Following, in ACD chronic model, the NEUG decreased significantly the edematogenyc process in all avaliated doses 0,04, 0,08 and 0,16 mg/ear, by 44,9, 48,2 and 57,5% respectively. Based on previous results obtained through acute ACD method and macroscopic evaluation of the chronic injuries, we continued the study with the NEUG 0,16 mg/ear dose. The NEUG topical application was capable to module the tecidual levels of TNF-α, IFN-γ e IL-4, decreased the pró-inflammatory of such substances production by 46,4, 50,3 e 28,3%, respectively. Moreover, the NEUG daily topical administration increased the IL-10 levels in inflamed ear by 121,9%, compared with the oxazolone group. Additionally, NEUG reduced the epidermis hyperplasia, decreased the mast cell concentration in inflammatory site as well as partially kept the dermis structure reversing the edematogenic process and infiltrade inflammatory, analyzed by histopatologic methods. Unprecedentedly, we evaluated the NEUG eficace in allergic contact dermatiti murine models, showed that the eugenol encapsulation provided changes in biological characteristic, resignifying use of the active principle by topical route and revealed a therapeutic strategic promissor for acute and chronic ACD treatment.