S B Waller1, M B Cleff2, D F Dalla Lana3, C B de Mattos2, K A Guterres2, R A Freitag4, E S V Sallis5, A M Fuentefria3, J R B de Mello6, R O de Faria1, M C A Meireles1. 1. Department of Preventive Veterinary, Faculty of Veterinary, Federal University of Pelotas, Pelotas/RS, Brazil. 2. Department of Veterinary Clinics, Faculty of Veterinary, Federal University of Pelotas, 96010-900 Pelotas/RS, Brazil. 3. Post-Graduate Program of Pharmaceutical Sciences, Federal University of Rio Grande do Sul, 90610-000 Porto Alegre/RS, Brazil. 4. Department of Organic Chemistry, Institute of Chemistry and Geoscience, Federal University of Pelotas, 96010-900 Pelotas/RS, Brazil. 5. Department of Animal Pathology, Faculty of Veterinary, Federal University of Pelotas, 96010-900 Pelotas/RS, Brazil. 6. Department of Pharmacology, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul (UFRGS), 90050-170 Porto Alegre/RS, Brazil.
Abstract
INTRODUCTION: Itraconazole is the first-choice option to treat human and animal sporotrichosis. However, the emergence of itraconazole-resistant strains has encouraged research on new active antifungals. Among them, the essential oil of rosemary (Rosmarinus officinalis Linn., Lamiaceae) has shown antifungal activity in vitro. OBJECTIVE: Assessing, for the first time, the effectiveness of rosemary essential oil in vivo in experimental cutaneous sporotrichosis, as well as its chemical composition and action mode. METHODS: Itraconazole-resistant Sporothrix brasiliensis was inoculated in the left foot pad of 30 Wistar rats, which were randomized (n=10) for treatment with saline solution (control, CONT), itraconazole (ITRA, 10 mg/kg) and rosemary oil (ROSM, 250 mg/kg) for 30 days at an oral dose of 1 mL, daily. Clinical evolution, histopathology and fungal burden were investigated. GC-MS was used for chemical analysis; sorbitol protection and ergosterol effect were used to evaluate the action mechanism of rosemary oil. RESULTS: ROSM was the only group evolving to skin lesion remission, lack of edema and exudate, and mild-to-absent yeast cells. Rosemary oil delayed fungal spreading and protected systemic organs, mainly liver and spleen. The ROSM group presented lower fungal load than that observed for the CONT and ITRA groups (p<0.05). Antifungal action took place at complexation level after ergosterol application. Most compounds were 1,8-cineole/eucalyptol (47.91%), camphor (17.92%), and α-pinene (11.52%). CONCLUSIONS: These findings have evidenced that rosemary oil is a promising antifungal to treat sporotrichosis, since it protects systemic organs from fungal spread.
INTRODUCTION: Itraconazole is the first-choice option to treat human and animal sporotrichosis. However, the emergence of itraconazole-resistant strains has encouraged research on new active antifungals. Among them, the essential oil of rosemary (Rosmarinus officinalis Linn., Lamiaceae) has shown antifungal activity in vitro. OBJECTIVE: Assessing, for the first time, the effectiveness of rosemary essential oil in vivo in experimental cutaneous sporotrichosis, as well as its chemical composition and action mode. METHODS: Itraconazole-resistant Sporothrix brasiliensis was inoculated in the left foot pad of 30 Wistar rats, which were randomized (n=10) for treatment with saline solution (control, CONT), itraconazole (ITRA, 10 mg/kg) and rosemary oil (ROSM, 250 mg/kg) for 30 days at an oral dose of 1 mL, daily. Clinical evolution, histopathology and fungal burden were investigated. GC-MS was used for chemical analysis; sorbitol protection and ergosterol effect were used to evaluate the action mechanism of rosemary oil. RESULTS: ROSM was the only group evolving to skin lesion remission, lack of edema and exudate, and mild-to-absent yeast cells. Rosemary oil delayed fungal spreading and protected systemic organs, mainly liver and spleen. The ROSM group presented lower fungal load than that observed for the CONT and ITRA groups (p<0.05). Antifungal action took place at complexation level after ergosterol application. Most compounds were 1,8-cineole/eucalyptol (47.91%), camphor (17.92%), and α-pinene (11.52%). CONCLUSIONS: These findings have evidenced that rosemary oil is a promising antifungal to treat sporotrichosis, since it protects systemic organs from fungal spread.