Inibição fotodinâmica em Trichophyton rubrum e Paracoccidioides brasiliensis: ensaios in vitro e in vivo
The antimicrobial photodynamic inhibition (aPI) is a treatment that involves the use of a photosensitizer (PS) and a source of light. When this process occurs at presence of molecular oxygen different biological effectors are generated, resulting in the cell death. In the present study the effective...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2013 |
| País: | Brasil |
| Institución: | Universidade Federal de Minas Gerais (UFMG) |
| Repositorio: | Repositório Institucional da UFMG |
| Idioma: | portugués |
| OAI Identifier: | oai:repositorio.ufmg.br:1843/BUOS-9B9H2N |
| Acceso en línea: | http://hdl.handle.net/1843/BUOS-9B9H2N |
| Access Level: | acceso abierto |
| Palabra clave: | Inibição (e terapia) fotodinâmica antimicrobiana Estresse oxidativo e nitrosativo T rubrum Redução da carga fúngica Paracoccidioides brasiliensis Microbiologia Trichophyton rubrum Fotoquimioterapia Estresse oxidativo |
| Sumario: | The antimicrobial photodynamic inhibition (aPI) is a treatment that involves the use of a photosensitizer (PS) and a source of light. When this process occurs at presence of molecular oxygen different biological effectors are generated, resulting in the cell death. In the present study the effectiveness of aPI using toluidine blue (TBO) as PS and LED, 630 nm, as a source of light against a set of samples of T. rubrum and ofParacoccididoides brasiliensis was evaluated. Time kill curves were performed; production of reactive oxygen species (ROS), peroxinitrite (ONOO) and nitric oxide (NO) after aPI were quantified and susceptibility profiles of Trichophyton rubrum to ciclopioxolamine and of Paracoccidioides brasiliensis, in nonmelanized and melanized conditions, to itraconazole and amphotericin B were determined. In addition, the efficacy of antimicrobial photodynamic therapy to reduce the fungal burden at skin in an animal model of dermatophytosis by T. rubrum was evaluated. The results showed that aPI on optimized conditions was fungicidal, reducing up to 98% of T. rubrum and 99.95% of Paracoccidioides growth. The time kill curve assays showed that aPIreduced the fungal viability faster than the treatment with conventional antifungal drugs. This probably occurred because of the mechanism of action of each treatment. The generation of ROS, ONOO and NO during aPI was important to reduce the fungal viability. The in vivo analisys showed that photodynamic therapy was efficient in reducing the fungal burden in the skin without causing significant damage on the surrounding tissue. These results are pioneer and suggest that aPI could be a useful approach for the treatment of dermatophytosis. Lastly, our results showed that melanized Paracoccidioides cells were more resistant to antifungal treatments than nonmelanized cells, confirming previous evidences that melanin can alter the efficacy of conventional drugs and to aPI. |
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