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| Author(s): |
Cristiana de Melo Trinconi Tronco
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) |
| Defense date: | 2015-12-04 |
| Examining board members: |
Silvia Reni Bortolin Uliana;
Bartira Rossi Bergmann;
Frederic Jean Georges Frezard;
Alejandro Miguel Katzin;
Jeffrey Jon Shaw
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| Advisor: | Silvia Reni Bortolin Uliana |
| Abstract | |
Leishmaniasis is a parasitic disease with wide distribution and limited treatment. Recent reports demonstrate that tamoxifen is an effective drug for experimental leishmaniasis treatment. In this work, we evaluated the combined therapy of tamoxifen with current drugs used in leishmaniasis chemotherapy. The drug interaction was additive both, in vitro and in vivo. We also evaluated tamoxifen effect on in Leishmania sphingolipids biosynthesis. We found a reduction in phosphatidylinositol and inositol phosphorylceramide (IPC) synthesis and an accumulation of acilceramide. The reduction in IPC biosynthesis could not be assigned to the reduction observed in inositol transport, but probably is related to IPC synthase inhibition. These results show new strategies to circumvent shortcomings of leishmaniasis treatment using tamoxifen, a multitarget drug in Leishmania and widely used in the chemotherapy of breast cancer. (AU) | |
| FAPESP's process: | 11/18858-6 - TAMOXIFEN AS AN ANTI-LEISHMANIAL DRUG: ACTIVITY IN COMBINED THERAPEUTIC SCHEMES AND STUDY OF THE MECHANISM OF ACTION |
| Grantee: | Cristiana de Melo Trinconi Tronco |
| Support Opportunities: | Scholarships in Brazil - Doctorate |