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dc.contributor.author
de Silva Rodrigues, Jean Hernrique  
dc.contributor.author
Stein, Jasmin  
dc.contributor.author
Strauss, Mariana  
dc.contributor.author
Rivarola, Hector Walter  
dc.contributor.author
Ueda Nakamura, Tania  
dc.contributor.author
Nakamura, Celso Vaturu  
dc.contributor.author
Duszenko, Michael  
dc.date.available
2018-09-04T18:20:00Z  
dc.date.issued
2016-04  
dc.identifier.citation
de Silva Rodrigues, Jean Hernrique; Stein, Jasmin; Strauss, Mariana; Rivarola, Hector Walter; Ueda Nakamura, Tania; et al.; Clomipramine kills Trypanosoma brucei by apoptosis; Elsevier Gmbh; International Journal of Medical Microbiology (print); 16; 4; 4-2016; 1438-4221  
dc.identifier.issn
1438-4221  
dc.identifier.uri
http://hdl.handle.net/11336/58264  
dc.description.abstract
Drug repositioning, i.e. use of existing medicals to treat a different illness, is especially rewarding for neglected tropical diseases (NTD), since in this field the pharmaceutical industry is rather reluctant to spend vast investments for drug development. NTDs afflict primarily poor populations in under-developed countries, which minimizes financial profit. Here we investigated the trypanocidal effect of clomipramine, a commercial antipsychotic drug, on Trypanosoma brucei. The data showed that this drug killed the parasite with an IC50 of about 5 μM. Analysis of the involved cell death mechanism revealed furthermore an initial autophagic stress response and finally the induction of apoptosis. The latter was substantiated by a set of respective markers such as phosphatidylserine exposition, DNA degradation, loss of the inner mitochondrial membrane potential and characteristic morphological changes. Clomipramine was described as a trypanothione inhibitor, but as judged from our results it also showed DNA binding capacities and induced substantial morphological changes. We thus consider it likely that the drug induces a multifold adverse interaction with the parasite?s physiology and induces stress in a way that trypanosomes cannot cope with.  
dc.format
application/pdf  
dc.language.iso
eng  
dc.publisher
Elsevier Gmbh  
dc.rights
info:eu-repo/semantics/openAccess  
dc.rights.uri
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/  
dc.subject
Apoptosis  
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Clomipramine  
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Sleeping Sickness  
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Otras Ciencias Biológicas  
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Ciencias Biológicas  
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CIENCIAS NATURALES Y EXACTAS  
dc.title
Clomipramine kills Trypanosoma brucei by apoptosis  
dc.type
info:eu-repo/semantics/article  
dc.type
info:ar-repo/semantics/artículo  
dc.type
info:eu-repo/semantics/publishedVersion  
dc.date.updated
2018-08-29T18:39:20Z  
dc.journal.volume
16  
dc.journal.number
4  
dc.journal.pagination
1438-4221  
dc.journal.pais
Alemania  
dc.description.fil
Fil: de Silva Rodrigues, Jean Hernrique. Universidade Estadual de Maringá; Brasil. University of Tübingen. Interfaculty Institute of Biochemistry; Alemania  
dc.description.fil
Fil: Stein, Jasmin. University Of Tübingen, Interfaculty Institute Of Bioch; Alemania  
dc.description.fil
Fil: Strauss, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina  
dc.description.fil
Fil: Rivarola, Hector Walter. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina  
dc.description.fil
Fil: Ueda Nakamura, Tania. Universidade Estadual de Maringa; Brasil  
dc.description.fil
Fil: Nakamura, Celso Vaturu. Universidade Estadual de Maringa; Brasil  
dc.description.fil
Fil: Duszenko, Michael. University Of Tübingen, Interfaculty Institute Of Bioch; Alemania  
dc.journal.title
International Journal of Medical Microbiology (print)  
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1016/j.ijmm.2016.03.009  
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S1438422116300297