nÃo hà / O aumento nos Ãltimos anos de indivÃduos imunocomprometidos, como portadores da SÃndrome da ImunodeficiÃncia Adquirida, de doenÃas malignas, transplantados e outros usuÃrios de terapias imunossupressoras, favorece o surgimento de infecÃÃes oportunistas, principalmente as de teor fÃngico, como a candidÃase e a criptococose. Apesar de a terapia antifÃngica atual ser eficiente na maioria dos casos, algumas vezes fazem-se necessÃrias novas drogas que atuem como alternativa ou como coadjuvantes no tratamento para potencializar o efeito dos antifÃngicos utilizados. As estatinas sÃo fÃrmacos hipolipemiantes mais prescritos mundialmente para doenÃas cardiovasculares. Entretanto, recentemente, tem sido descritos outros efeitos benÃficos destas drogas, como, por exemplo, o controle de infecÃÃes. Este trabalho teve como objetivo determinar a atividade antifÃngica in vitro das estatinas ante 51 cepas de Candida, sendo 16 de C. albicans, 11 de C. krusei, 12 de C. tropicalis e 12 de C. parapsilosis, e 25 cepas de Cryptococcus, sendo 12 de C. gattii e 13 de C. neoformans, por meio de testes de microdiluiÃÃo em caldo, segundo documento M27-A3 padronizado pelo CLSI. O intervalo de concentraÃÃo testado para pravastatina foi de 50 a 0,0977 mg/mL, para sinvastatina, 1 a 0,0020 mg/mL e para atorvastatina, 10 a 0,0200 mg/mL. Pravastatina inibiu 37 leveduras do gÃnero Candida apresentando concentraÃÃo inibitÃria mÃnima (CIM) na faixa de 1,56 a 6,25 mg /mL e as cepas restantes nÃo foram inibidas mesmo na maior concentraÃÃo testada (50 mg /mL), enquanto que sinvastatina e atorvastatina apresentaram atividade antifÃngica sobre todas as 51 cepas avaliadas, apresentando CIMs de 0,02 a 1 mg / mL e 0,04 a 5,00 mg / mL, respectivamente. Para o gÃnero Cryptococcus, apenas 4 cepas foram inibidas ante a pravastatina (CIM = 25 mg / mL), por outro lado, sinvastatina inibiu todas as 25 cepas (CIM = 0,06 a 1 mg / mL), e atorvastatina apenas 8 cepas (CIM = 0,62 a 2,5 mg / mL), sendo que as 17 restantes nÃo foram inibidas mesmo na maior concentraÃÃo testada ( ≥ 10 mg / mL). Foi determinada concentraÃÃo fungicida mÃnima (CFM) de pravastatina sobre 15 cepas do gÃnero Candida (CFM = 3,12 a 25 mg / mL), de sinvastatina sobre 34 cepas (CFM = 0,03 a 1 mg / mL), e de atorvastatina sobre 16 cepas (CFM = 0,04 a 0,31 mg / mL). Para o gÃnero Cryptococcus, das 25 cepas testadas, pravastatina exibiu CFM sobre apenas 3 cepas (CFM = 50 mg / mL), sinvastatina sobre 21 cepas (CFM = 0,12 a 1 mg / mL), e atorvastatina sobre 1 cepa (CFM = 1 mg / mL). Esta atividade inibitÃria in vitro de estatinas sobre espÃcies de Candida e Cryptococcus, abre uma perspectiva importante para a investigaÃÃo do possÃvel uso destas drogas com finalidade antifÃngica in vivo. / In the past years, fungal opportunistic infections, especially, candidiasis and cryptococcosis, have become more frequent because of the increase in the number of immunocompromised individuals, such as AIDS, transplant and cancer patients and those that are on immunosuppressive therapy. In spite of being effective, sometimes it is necessary to use new drugs as alternatives or as adjuvants in order to potentiate the effect of the classical antifungal therapy. Statins are the most prescribed hypolipemiant drugs worldwide for preventing cardiovascular diseases. However, other benefic effects for these drugs have been described, such as the control of infections. This work aimed at determining the antifungal activity of statins against Candida spp. and Cryptococcus spp. The minimum inhibitory concentrations (MICs) for three different statins (pravastatin, simvastatin and atorvastatin) were determined against 51 strains of Candida spp. (16 C. albicans, 11 C.krusei, 12 C. tropicalis and 12 C. parapsilosis) and 25 strains of Cryptococcus spp. (12 C. gattii and 13 C. neoformans), through broth microdilution assay, according to the Clinical Laboratory Standards Institute (CLSI - Document M27-A3). The concentration tested for pravastatin ranged from 50 to 0.0977 mg/mL, for simvastatin, it ranged from 1 to 0.0020 mg/mL and, for atorvastatin, it varied from 10 to 0.0200 mg/mL. Pravastatin inhibited 37 Candida strains, with MICs varying from 1.56 to 6.25 mg/mL and the remaining strains were not inhibited, even at the highest concentration tested (50 mg/mL). Simvastatin and atorvastatin, on the other hand, inhibited all 51 Candida strains evaluated, presenting MICs ranging from 0.02 to 1 mg/mL and from 0.04 to 5 mg/mL, respectively. Concerning Cryptococcus spp., only four strains were inhibited by pravastatin (MIC=25 mg/mL), while all 25 strains were inhibited by simvastatin (0.06≤MIC≤1 mg/mL) and eight were inhibited by atorvastatin (0.62≤MIC≤2.5 mg/mL) and the remaining 17 were not susceptible to the highest atorvastatin concentration tested (10 mg/mL). The minimum fungicidal concentrations (MFCs) for the tested statins were also determined. The MFC for pravastatin against Candida spp. was determined against 15 strains (3.12≤MIC≤25 mg/mL). The MFC values for simvastatin were determined for 34 strains of Candida spp. (0.03≤MFC≤1 mg/mL), while those for atorvastatin were determined against 16 strains (0.04≤MFC≤0,31 mg/mL). Concerning Cryptococcus spp., the 25 strains tested, MFC values for pravastatin were found against three strains (MFC=50 mg/mL), while those for simvastatin were determined against 21 strains (0.12≤MFC≤1 mg/mL) and those for atorvastatin were determined against one single strain (MFC=1 mg/mL). This in vitro inhibitory activity of statins against Candida spp. and Cryptococcus spp. creates an important perspective for the use of these drugs in vivo in order to control fungal infections.
| Identifer | oai:union.ndltd.org:IBICT/oai:www.teses.ufc.br:6403 |
| Date | 29 September 2011 |
| Creators | Elizabeth Ribeiro Yokobatake Souza |
| Contributors | Raimunda SÃmia Nogueira Brilhante, Josà JÃlio Costa Sidrim, Marcos FÃbio Gadelha Rocha |
| Publisher | Universidade Federal do CearÃ, Programa de PÃs-GraduaÃÃo em Microbiologia MÃdica, UFC, BR |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/masterThesis |
| Format | application/pdf |
| Source | reponame:Biblioteca Digital de Teses e Dissertações da UFC, instname:Universidade Federal do Ceará, instacron:UFC |
| Rights | info:eu-repo/semantics/openAccess |
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