Avaliações de creme cicatrizante com extratos vegetais de urucum e trigo associado à imunomodulação junto ao tratamento convencional da esporotricose

Abstract

Sporotrichosis is the most important subcutaneous implantation mycosis in Brazil, caused by fungi of the Sporothrix schenckii complex, frequently affecting humans, dogs, and especially cats. Feline sporotrichosis and its zoonotic transmission have been increasing in Brazil, and cases of treatment failure with conventional therapies have already been reported. This study aimed to evaluate the efficacy of formulations containing plant-derived actives from Bixa orellana L. (annatto) and Triticum aestivum (wheat), as well as thymomodulin as adjuvants in the treatment of cutaneous sporotrichosis lesions, through in vitro and in vivo experiments in murine models and naturally infected cats.Initially, oleaginous extracts of annatto and aqueous and ethanolic extracts of wheat were obtained. Subsequently, two distinct pharmaceutical formulations were developed: one containing annatto oil and aqueous wheat extract (LCFT2001), and another containing annatto oil and ethanolic wheat extract (LCFT2002). In the in vitro study, the formulations were tested against Sporothrix isolates to assess antifungal susceptibility and synergism. The ethanolic wheat extract and annatto oil showed individual antifungal activity; however, when combined, they exhibited antagonistic effects. In the in vivo murine model, sporotrichosis was experimentally induced in Wistar rats, which were treated daily with: topical formulation LCFT2001 (GF1); topical formulation LCFT2002 (GF2); thymomodulin, itraconazole, and LCFT2001 (GITF1); thymomodulin, itraconazole, and LCFT2002 (GITF2); thymomodulin and itraconazole (GIT); thymomodulin alone (GT); positive control with itraconazole (GI); and a negative control without treatment (GCN). At days 4, 11, 18, 30, and 42, treatment effectiveness was evaluated through clinical data, mycological analysis (fungal load quantification and re-isolation), and histological assessment (tissue lesion pattern). It was observed that groups GF2, GITF1, and GITF2 showed distinct clinical progression, with more pronounced inflammatory signs early on, which decreased over the course of treatment. The GIT, GITF1, and GITF2 groups significantly reduced fungal load compared to controls. Histologically, these groups exhibited greater lymphocytic infiltration and fewer fungal cells; in addition, GITF2 showed mature fibrosis earlier than other groups. In the clinical trial in cats, the effects of thymomodulin and LCFT2002 were evaluated in cats with naturally acquired sporotrichosis. This was a prospective study analyzing treatments with itraconazole, thymomodulin, and LCFT2002 topical formulation (GITF); itraconazole and thymomodulin (GIT); itraconazole and LCFT2002 (GIF); and itraconazole alone (GI) over a 60-day period. Cats underwent clinical, cytological (yeast quantification in lesions), and histological evaluations (tissue lesion pattern).It was found that the GIT group had the best clinical outcome, with no therapeutic failures, while the GITF group showed faster reduction in fungal cells and lesion areas. Histologically, the GITF group showed increased numbers of lymphocytes, epithelioid cells, and fibrosis during treatment. These findings highlight that the use of thymomodulin and topical LCFT2002 as adjuvants enhances the inflammatory response, potentiating the effects of itraconazole. This thesis resulted in three scientific articles submitted to the journals Revista Observatório de La Economía Latinoamericana, Mycoses, and Ciência Animal.