3'Deoxiadenosina e deoxicoformicina no tratamento de camundongos infectados experimentalmente com Trypanosoma evansi
Autor(a) principal: | |
---|---|
Data de Publicação: | 2014 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Repositório Institucional Manancial UFSM |
Texto Completo: | http://repositorio.ufsm.br/handle/1/4102 |
Resumo: | Trypanosoma evansi is a pathogenic trypanosomatid with world distribution, which may cause big economic losses and affect almost all mammalian species. One of the most affected species is horses, which may develop a disease known as Mal das cadeiras. There are several clinical signs and pathologies resulting from this parasite infection. The acute phase is characterized by intermittent fever, subcutaneous edema, progressive anemia, blindness, lethargy and hemostatic abnormalities. In the chronic phase, animals exhibit cachexia, edema, incoordination and paralysis. The most common treatment for this infection is the use of drugs; however, these drugs have a moderate efficacy, and they may present toxicity, especially to kidney and liver. Thus, it is important to study new therapies for the treatment of the disease caused by T. evansi. The aim of this study was to investigate the anti-trypanosomal effect of the treatment with 3‟deoxyadenosine (cordycepin - adenosine analogue) combined with deoxycoformycin (pentostatin - inhibitor of the adenosine deaminase (ADA) enzyme and deoxyadenosine analogue) in mice experimentally infected with T. evansi. Furthermore, we also verified the influence of the therapy in the hematologic, biochemical and ADA activity parameters, makers of cell viability and toxicity, oxidative stress and histopathology analyses. These analyses were divided into three experiments. The first one showed that the combination of cordycepin (2mgkg-1) and pentostatin (2mgkg-1) was 100% effective in the T. evansi-infected groups; however, the treatment increased significantly the liver enzyme levels, which were accompanied by histological lesions in the liver and kidneys. The second experiment showed a reduction in the levels of plasma total protein in healthy mice and treated with 1mg/kg cordycepin or 1mg/kg pentostatin. The animals treated with pentostatin alone or associated with cordycepin showed an ADA activity significantly reduced. The third experiment showed that the combination of cordycepin (2.0 mg kg-1) and pentostatin (0.2, 0.5, 1.0, 2.0 mg kg-1) is effective in the clearance of T. evansi, although at higher concentrations (cordycepin 2mg kg-1 and pentostatin 2mg kg-1), toxicity was observed. Therefore, the dose cordycepin 2.0 mg kg-1 in combination with pentostatin 0.2 mg kg-1 was recommended as a therapeutic option. This combination showed to be 100% effective in the experimentally infected animals and presented no toxicity to the animals. |
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2017-06-142017-06-142014-12-01ROSA, Luciana Dalla. 3'Deoxyadenosin and deoxycoformycin treatment of experimentally infected mice with Trypanosoma evansi. 2014. 81 f. Tese (Doutorado em Medicina Veterinária) - Universidade Federal de Santa Maria, Santa Maria, 2014.http://repositorio.ufsm.br/handle/1/4102Trypanosoma evansi is a pathogenic trypanosomatid with world distribution, which may cause big economic losses and affect almost all mammalian species. One of the most affected species is horses, which may develop a disease known as Mal das cadeiras. There are several clinical signs and pathologies resulting from this parasite infection. The acute phase is characterized by intermittent fever, subcutaneous edema, progressive anemia, blindness, lethargy and hemostatic abnormalities. In the chronic phase, animals exhibit cachexia, edema, incoordination and paralysis. The most common treatment for this infection is the use of drugs; however, these drugs have a moderate efficacy, and they may present toxicity, especially to kidney and liver. Thus, it is important to study new therapies for the treatment of the disease caused by T. evansi. The aim of this study was to investigate the anti-trypanosomal effect of the treatment with 3‟deoxyadenosine (cordycepin - adenosine analogue) combined with deoxycoformycin (pentostatin - inhibitor of the adenosine deaminase (ADA) enzyme and deoxyadenosine analogue) in mice experimentally infected with T. evansi. Furthermore, we also verified the influence of the therapy in the hematologic, biochemical and ADA activity parameters, makers of cell viability and toxicity, oxidative stress and histopathology analyses. These analyses were divided into three experiments. The first one showed that the combination of cordycepin (2mgkg-1) and pentostatin (2mgkg-1) was 100% effective in the T. evansi-infected groups; however, the treatment increased significantly the liver enzyme levels, which were accompanied by histological lesions in the liver and kidneys. The second experiment showed a reduction in the levels of plasma total protein in healthy mice and treated with 1mg/kg cordycepin or 1mg/kg pentostatin. The animals treated with pentostatin alone or associated with cordycepin showed an ADA activity significantly reduced. The third experiment showed that the combination of cordycepin (2.0 mg kg-1) and pentostatin (0.2, 0.5, 1.0, 2.0 mg kg-1) is effective in the clearance of T. evansi, although at higher concentrations (cordycepin 2mg kg-1 and pentostatin 2mg kg-1), toxicity was observed. Therefore, the dose cordycepin 2.0 mg kg-1 in combination with pentostatin 0.2 mg kg-1 was recommended as a therapeutic option. This combination showed to be 100% effective in the experimentally infected animals and presented no toxicity to the animals.Trypanosoma evansi é um tripanossomatídeo patogênico de distribuição mundial, causador de grandes prejuízos econômicos, podendo afetar várias espécies de mamíferos, principalmente equinos, espécie na qual produz uma doença conhecida como Mal das cadeiras . Muitos são os sinais clínicos e as patologias decorrentes da infecção por este parasito. A fase aguda da doença é caracterizada pelo surgimento de febre intermitente, edema subcutâneo, anemia progressiva, cegueira, letargia e alterações hemostáticas. Na fase crônica os animais apresentam caquexia, edema, incoordenação motora e paralisia de membros posteriores. O tratamento para essa infecção é medicamentoso, no entanto, os produtos químicos disponíveis possuem eficácia moderada e toxicidade, especialmente para os rins e fígado. Assim, é importante a pesquisa de terapias alternativas para o tratamento da doença causada pelo T. evansi. O objetivo deste estudo foi investigar a susceptibilidade do T. evansi à 3′-deoxiadenosina (cordicepina - análogo da adenosina) associada a deoxicoformicina (pentostatina - inibidor da adenosina deaminase (ADA) e análogo da desoxiadenosina) em camundongos infectados experimentalmente e verificar a influência desta terapia nos parâmetros hematológicos, bioquímicos, de atividade da ADA, marcadores de viabilidade e toxicidade celular e de estresse oxidativo e análise histopatológica. Essas análises foram divididas em três experimentos. O primeiro experimento demonstrou que a combinação de cordicepina (2 mg kg−1) e pentostatina (2 mg kg−1) foi 100% efetiva na cura dos animais infectados, mas esse tratamento ocasionou um aumento significativo nos níveis de enzimas hepáticas e produziu lesões histológicas no fígado e rins. O segundo experimento demonstrou uma reducão nos níveis de proteínas plasmáticas totais nos roedores sadios e tratados com 1mg/kg de cordicepina ou 1mg/kg de pentostatina, tendo os animais pertencentes aos grupos tratados com pentostatina isolada ou associada a cordicepina, uma diminuição da atividade da ADA. O terceiro experimento mostrou que as combinações de cordicepina (2,0 mg kg-1) e pentostatina (0,2; 0,5; 1,0; 2,0 mg kg1) foram eficazes na cura de animais infectados, mas na dose mais alta (cordicepina 2mg kg-1 e pentostatina 2mg kg-1), foi observado toxicidade elevada. A dose de cordicepina 2.0 mg kg-1 associada a pentostatina 0.2 mg kg-1 foi recomendada como opção terapêutica, com 100% de cura dos animais infectados experimentalmente sem apresentar toxicidade aos mesmos.Coordenação de Aperfeiçoamento de Pessoal de Nível Superiorapplication/pdfporUniversidade Federal de Santa MariaPrograma de Pós-Graduação em Medicina VeterináriaUFSMBRMedicina VeterináriaCordicepinaPentostatinaAdenosinaTripanossomatídeoDose idealCordycepinPentostatinAdenosineTrypanosomatidOptimal doseCNPQ::CIENCIAS AGRARIAS::MEDICINA VETERINARIA3'Deoxiadenosina e deoxicoformicina no tratamento de camundongos infectados experimentalmente com Trypanosoma evansi3'Deoxyadenosin and deoxycoformycin treatment of experimentally infected mice with Trypanosoma evansiinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisMonteiro, Silvia Gonzalezhttp://lattes.cnpq.br/3762606653182779Stainki, Daniel Roulimhttp://lattes.cnpq.br/0445408645323550Leal, Marta Lizandra do Rêgohttp://lattes.cnpq.br/6859797230596402Vaucher, Rodrigo de Almeidahttp://lattes.cnpq.br/0953074420467371Krause, Luciana Maria Fontanarihttp://lattes.cnpq.br/9844890896121847http://lattes.cnpq.br/2030771484016188Dalla Rosa, Luciana500500000007400300300300300300300f658c142-7522-4cd5-a133-f2479652bf3168ab40b9-11d0-4861-b037-0bdb425b9ab4f2c77936-cacd-4d88-a79f-1f941457a6956e07b261-9fab-4e13-b45e-b965edb04f265fdb7e57-59de-4afd-be5f-3f491fff9113a45db657-fbef-4efc-a2e6-1b1ebab5c203info:eu-repo/semantics/openAccessreponame:Repositório Institucional Manancial UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALDALLA ROSA, LUCIANA.pdfapplication/pdf2130879http://repositorio.ufsm.br/bitstream/1/4102/1/DALLA%20ROSA%2c%20LUCIANA.pdf0a6fae52144ed91d1886775e518c03fbMD51TEXTDALLA ROSA, LUCIANA.pdf.txtDALLA ROSA, LUCIANA.pdf.txtExtracted texttext/plain157852http://repositorio.ufsm.br/bitstream/1/4102/2/DALLA%20ROSA%2c%20LUCIANA.pdf.txtad5f64b67b40f377fafcb0d867392211MD52THUMBNAILDALLA ROSA, LUCIANA.pdf.jpgDALLA ROSA, LUCIANA.pdf.jpgIM Thumbnailimage/jpeg4868http://repositorio.ufsm.br/bitstream/1/4102/3/DALLA%20ROSA%2c%20LUCIANA.pdf.jpgb1444b5252253a1f1e04a2522b8a675aMD531/41022023-09-13 10:45:48.907oai:repositorio.ufsm.br:1/4102Repositório Institucionalhttp://repositorio.ufsm.br/PUBhttp://repositorio.ufsm.br/oai/requestouvidoria@ufsm.bropendoar:39132023-09-13T13:45:48Repositório Institucional Manancial UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.por.fl_str_mv |
3'Deoxiadenosina e deoxicoformicina no tratamento de camundongos infectados experimentalmente com Trypanosoma evansi |
dc.title.alternative.eng.fl_str_mv |
3'Deoxyadenosin and deoxycoformycin treatment of experimentally infected mice with Trypanosoma evansi |
title |
3'Deoxiadenosina e deoxicoformicina no tratamento de camundongos infectados experimentalmente com Trypanosoma evansi |
spellingShingle |
3'Deoxiadenosina e deoxicoformicina no tratamento de camundongos infectados experimentalmente com Trypanosoma evansi Dalla Rosa, Luciana Cordicepina Pentostatina Adenosina Tripanossomatídeo Dose ideal Cordycepin Pentostatin Adenosine Trypanosomatid Optimal dose CNPQ::CIENCIAS AGRARIAS::MEDICINA VETERINARIA |
title_short |
3'Deoxiadenosina e deoxicoformicina no tratamento de camundongos infectados experimentalmente com Trypanosoma evansi |
title_full |
3'Deoxiadenosina e deoxicoformicina no tratamento de camundongos infectados experimentalmente com Trypanosoma evansi |
title_fullStr |
3'Deoxiadenosina e deoxicoformicina no tratamento de camundongos infectados experimentalmente com Trypanosoma evansi |
title_full_unstemmed |
3'Deoxiadenosina e deoxicoformicina no tratamento de camundongos infectados experimentalmente com Trypanosoma evansi |
title_sort |
3'Deoxiadenosina e deoxicoformicina no tratamento de camundongos infectados experimentalmente com Trypanosoma evansi |
author |
Dalla Rosa, Luciana |
author_facet |
Dalla Rosa, Luciana |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Monteiro, Silvia Gonzalez |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/3762606653182779 |
dc.contributor.referee1.fl_str_mv |
Stainki, Daniel Roulim |
dc.contributor.referee1Lattes.fl_str_mv |
http://lattes.cnpq.br/0445408645323550 |
dc.contributor.referee2.fl_str_mv |
Leal, Marta Lizandra do Rêgo |
dc.contributor.referee2Lattes.fl_str_mv |
http://lattes.cnpq.br/6859797230596402 |
dc.contributor.referee3.fl_str_mv |
Vaucher, Rodrigo de Almeida |
dc.contributor.referee3Lattes.fl_str_mv |
http://lattes.cnpq.br/0953074420467371 |
dc.contributor.referee4.fl_str_mv |
Krause, Luciana Maria Fontanari |
dc.contributor.referee4Lattes.fl_str_mv |
http://lattes.cnpq.br/9844890896121847 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/2030771484016188 |
dc.contributor.author.fl_str_mv |
Dalla Rosa, Luciana |
contributor_str_mv |
Monteiro, Silvia Gonzalez Stainki, Daniel Roulim Leal, Marta Lizandra do Rêgo Vaucher, Rodrigo de Almeida Krause, Luciana Maria Fontanari |
dc.subject.por.fl_str_mv |
Cordicepina Pentostatina Adenosina Tripanossomatídeo Dose ideal |
topic |
Cordicepina Pentostatina Adenosina Tripanossomatídeo Dose ideal Cordycepin Pentostatin Adenosine Trypanosomatid Optimal dose CNPQ::CIENCIAS AGRARIAS::MEDICINA VETERINARIA |
dc.subject.eng.fl_str_mv |
Cordycepin Pentostatin Adenosine Trypanosomatid Optimal dose |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS AGRARIAS::MEDICINA VETERINARIA |
description |
Trypanosoma evansi is a pathogenic trypanosomatid with world distribution, which may cause big economic losses and affect almost all mammalian species. One of the most affected species is horses, which may develop a disease known as Mal das cadeiras. There are several clinical signs and pathologies resulting from this parasite infection. The acute phase is characterized by intermittent fever, subcutaneous edema, progressive anemia, blindness, lethargy and hemostatic abnormalities. In the chronic phase, animals exhibit cachexia, edema, incoordination and paralysis. The most common treatment for this infection is the use of drugs; however, these drugs have a moderate efficacy, and they may present toxicity, especially to kidney and liver. Thus, it is important to study new therapies for the treatment of the disease caused by T. evansi. The aim of this study was to investigate the anti-trypanosomal effect of the treatment with 3‟deoxyadenosine (cordycepin - adenosine analogue) combined with deoxycoformycin (pentostatin - inhibitor of the adenosine deaminase (ADA) enzyme and deoxyadenosine analogue) in mice experimentally infected with T. evansi. Furthermore, we also verified the influence of the therapy in the hematologic, biochemical and ADA activity parameters, makers of cell viability and toxicity, oxidative stress and histopathology analyses. These analyses were divided into three experiments. The first one showed that the combination of cordycepin (2mgkg-1) and pentostatin (2mgkg-1) was 100% effective in the T. evansi-infected groups; however, the treatment increased significantly the liver enzyme levels, which were accompanied by histological lesions in the liver and kidneys. The second experiment showed a reduction in the levels of plasma total protein in healthy mice and treated with 1mg/kg cordycepin or 1mg/kg pentostatin. The animals treated with pentostatin alone or associated with cordycepin showed an ADA activity significantly reduced. The third experiment showed that the combination of cordycepin (2.0 mg kg-1) and pentostatin (0.2, 0.5, 1.0, 2.0 mg kg-1) is effective in the clearance of T. evansi, although at higher concentrations (cordycepin 2mg kg-1 and pentostatin 2mg kg-1), toxicity was observed. Therefore, the dose cordycepin 2.0 mg kg-1 in combination with pentostatin 0.2 mg kg-1 was recommended as a therapeutic option. This combination showed to be 100% effective in the experimentally infected animals and presented no toxicity to the animals. |
publishDate |
2014 |
dc.date.issued.fl_str_mv |
2014-12-01 |
dc.date.accessioned.fl_str_mv |
2017-06-14 |
dc.date.available.fl_str_mv |
2017-06-14 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/doctoralThesis |
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doctoralThesis |
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publishedVersion |
dc.identifier.citation.fl_str_mv |
ROSA, Luciana Dalla. 3'Deoxyadenosin and deoxycoformycin treatment of experimentally infected mice with Trypanosoma evansi. 2014. 81 f. Tese (Doutorado em Medicina Veterinária) - Universidade Federal de Santa Maria, Santa Maria, 2014. |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/4102 |
identifier_str_mv |
ROSA, Luciana Dalla. 3'Deoxyadenosin and deoxycoformycin treatment of experimentally infected mice with Trypanosoma evansi. 2014. 81 f. Tese (Doutorado em Medicina Veterinária) - Universidade Federal de Santa Maria, Santa Maria, 2014. |
url |
http://repositorio.ufsm.br/handle/1/4102 |
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por |
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por |
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500500000007 |
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400 300 300 300 300 300 300 |
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Universidade Federal de Santa Maria |
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UFSM |
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BR |
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Medicina Veterinária |
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Universidade Federal de Santa Maria |
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