| Journal: | Memorias do Instituto Oswaldo Cruz |
| Database: | PERIÓDICA |
| System number: | 000452409 |
| ISSN: | 0074-0276 |
| Authors: | Nunes, Débora Cristina de Oliveira Silva1 Costa, Mônica Soares1 Bispo da Silva, Luiz Borges2 Ferro, Eloísa Amália Vieira2 Zóia, Mariana Alves Pereira1 Goulart, Luiz Ricardo1 Rodrigues, Renata Santos1 Rodrigues, Veridiana de Melo1 Yoneyama, Kelly Aparecida Geraldo1 |
| Institutions: | 1Universidade Federal de Uberlandia, Instituto de Biotecnologia, Uberlandia, Minas Gerais. Brasil 2Universidade Federal de Uberlandia, Instituto de Ciencias Biomedicas, Uberlandia, Minas Gerais. Brasil |
| Year: | 2022 |
| Volumen: | 117 |
| Country: | Brasil |
| Language: | Inglés |
| Document type: | Artículo |
| Approach: | Experimental, aplicado |
| English abstract | BACKGROUND Leishmania parasites cause leishmaniasis that range from self-limiting cutaneous lesions to more serious forms of the disease. The search for potential drug targets focusing on biochemical and metabolic pathways revealed the sterol biosynthesis inhibitors (SBIs) as a promising approach. In this class of inhibitors is found ketoconazole, a classical inhibitor of 14α-methysterol 14-demethylase. OBJECTIVE The present study aimed to better understand the biological response of Leishmania (Leishmania) amazonensis promastigotes at the cellular level after ketoconazole treatment. METHODS Herein, techniques, such as fluorimetry, flow cytometry, fluorescence microscopy, electron and scanning microscopy were used to investigate the cellular structures and to identify organelles affected by ketoconazole treatment. FINDINGS The study demonstrated, for the first time, the effect of ketoconazole on mitochondrion functioning and its probable relationship to cell cycle and death on L. (L.) amazonensis promastigotes (IFLA/BR/67/PH8 strain). MAIN CONCLUSIONS Ketoconazole-induced mitochondrial damages led to hyperpolarisation of this single organelle and autophagic vacuoles formation, as a parasite survival strategy. These damages did not reflect directly on the parasite cell cycle, but drove the parasites to death, making them susceptible to ketoconazole treatment in in vitro models |
| Disciplines: | Medicina |
| Keyword: | Parasitología, Farmacología, Leishmaniasis cutánea, Ketoconazol, Disfunción mitocondrial, Ergosterol, Leishmania amazonensis |
| Keyword: | Parasitology, Pharmacology, Cutaneous leishmaniasis, Ketoconazole, Mitochondrial dysfunction, Ergosterol, Leishmania amazonensis |
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