Atividade do ganciclovir em coelhos inoculados com o alfaherpesvírus equino 1
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Manancial - Repositório Digital da UFSM |
Texto Completo: | http://repositorio.ufsm.br/handle/1/20918 |
Resumo: | Equine alfaherpervirus 1 (EHV-1), a member of the family Herpesviridae and subfamily Alphaherpesvirinae, is distributed worldwide and associated with abortions, respiratory and neurological disease in horses. No specific treatment for diseases associated with EHV-1 in horses is available, since human anti-herpetic drugs are not yet routinely used in equine medicine. Thus, the objective of this study was to investigate the in vivo anti-herpetic activity of ganciclovir (GCV), a nucleoside analogue drug used in the herpesvirus infections treatment in humans, against EHV-1. In vivo tests were performed in rabbits, an experimental model for EHV-1 respiratory disease. For this, eighteen New Zealand rabbits with approximately 30 days of age were alocated into three groups of 6 animals each and each group received a treatment: (G1) inoculated by the intranasal route (IN) with RPMI medium; (G2) inoculated by the IN route with 107 DICC50 of EHV-1 strain Kentucky D and (G3) inoculated with EHV-1 and treated with GCV (intravenously with 2.5mg / kg every 12h for 7 days). After inoculation, the animals were monitored for clinical, virological and pathological aspects for 15 days. All animals of G2 developed systemic signs (apathy, inappetence) and respiratory signs of variable severity between days 3 and 13 pi. These signs consisted of serous to mucopurulent nasal secretion and mild to severe respiratory distress, as well as ocular secretion. In addition, these animals presented lower weight gain than the control (G1) and GCV (G3) groups at days 4, 6, 10, 12 and 14 pi (p <0.05). A rabbit from this group presented neurological signs and died on day three after inoculation (pi). The presence of the virus in the lung of this animal was confirmed by viral isolation and histopathology. In contrast, animals from the G3 group (inoculated with EHV-1 and treated with GCV) showed no systemic signs and presented only mild serous nasal secretion. The weight gain of these animals was similar to those of the control group (G1) and higher than those of the G2 group at days 4, 6, 10, 12 and 14 pi (p <0.05). Viral excretion in secretions and seroconversion to EHV-1 were observed in both G2 and G3 animals, with no evident differences in magnitude and duration. Thus, GCV treatment in rabbits infected with EHV-1 (G3) resulted in maintenance of daily weight gain, abolition of systemic signs and significant attenuation of respiratory clinical signs. These results are promising for the use of GCV in the treatment of herpes infections in horses. However, further studies investigating different doses, frequency of administration and activity when administered after the onset of clinical signs are necessary prior to its use in this species. |
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Atividade do ganciclovir em coelhos inoculados com o alfaherpesvírus equino 1Activity of ganciclovir in rabbits inoclulated with equid alphaherpesvirus 1AlfaherpesvírusEHV-1TerapiaGanciclovirModelo animalAlphaherpesvirusTherapyGanciclovirAnimal modelCNPQ::CIENCIAS AGRARIAS::MEDICINA VETERINARIAEquine alfaherpervirus 1 (EHV-1), a member of the family Herpesviridae and subfamily Alphaherpesvirinae, is distributed worldwide and associated with abortions, respiratory and neurological disease in horses. No specific treatment for diseases associated with EHV-1 in horses is available, since human anti-herpetic drugs are not yet routinely used in equine medicine. Thus, the objective of this study was to investigate the in vivo anti-herpetic activity of ganciclovir (GCV), a nucleoside analogue drug used in the herpesvirus infections treatment in humans, against EHV-1. In vivo tests were performed in rabbits, an experimental model for EHV-1 respiratory disease. For this, eighteen New Zealand rabbits with approximately 30 days of age were alocated into three groups of 6 animals each and each group received a treatment: (G1) inoculated by the intranasal route (IN) with RPMI medium; (G2) inoculated by the IN route with 107 DICC50 of EHV-1 strain Kentucky D and (G3) inoculated with EHV-1 and treated with GCV (intravenously with 2.5mg / kg every 12h for 7 days). After inoculation, the animals were monitored for clinical, virological and pathological aspects for 15 days. All animals of G2 developed systemic signs (apathy, inappetence) and respiratory signs of variable severity between days 3 and 13 pi. These signs consisted of serous to mucopurulent nasal secretion and mild to severe respiratory distress, as well as ocular secretion. In addition, these animals presented lower weight gain than the control (G1) and GCV (G3) groups at days 4, 6, 10, 12 and 14 pi (p <0.05). A rabbit from this group presented neurological signs and died on day three after inoculation (pi). The presence of the virus in the lung of this animal was confirmed by viral isolation and histopathology. In contrast, animals from the G3 group (inoculated with EHV-1 and treated with GCV) showed no systemic signs and presented only mild serous nasal secretion. The weight gain of these animals was similar to those of the control group (G1) and higher than those of the G2 group at days 4, 6, 10, 12 and 14 pi (p <0.05). Viral excretion in secretions and seroconversion to EHV-1 were observed in both G2 and G3 animals, with no evident differences in magnitude and duration. Thus, GCV treatment in rabbits infected with EHV-1 (G3) resulted in maintenance of daily weight gain, abolition of systemic signs and significant attenuation of respiratory clinical signs. These results are promising for the use of GCV in the treatment of herpes infections in horses. However, further studies investigating different doses, frequency of administration and activity when administered after the onset of clinical signs are necessary prior to its use in this species.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESO alfaherpesvírus equino 1 (EHV-1), membro da família Herpesviridae e subfamília Alphaherpesvirinae, possui distribuição mundial e tem sido associado com abortos, doença respiratória e neurológica em equinos. Como os fármacos anti-herpéticos de uso humano ainda não são rotineiramente utilizados em medicina equina, não há tratamento específico para as doenças associadas com o EHV-1. Assim, o objetivo deste trabalho foi investigar a atividade in vivo anti-EHV-1 do ganciclovir (GCV), um análogo de nucleosídeo utilizado no tratamento de infecções herpéticas em humanos. Os testes in vivo foram realizados em coelhos, um modelo experimental para a doença respiratória pelo EHV-1. Para isso, dezoito coelhos da raça Nova Zelândia com aproximadamente 30 dias de idade foram alocados em três grupos de 6 animais cada, e cada grupo recebeu um tratamento: (G1) inoculados pela via intranasal (IN) com meio RPMI; (G2) inoculados pela via IN com 107 DICC50 do EHV-1 cepa Kentucky D e (G3) inoculados com o EHV-1 e tratados com o GCV (via intravenosa, 2,5mg/kg a cada 12h por 7 dias). Após a inoculação, os animais foram monitorados nos aspectos clínicos, virológicos e patológicos durante 15 dias. Todos os animais do G2 apresentaram sinais sistêmicos (apatia, inapetência) e sinais clínicos respiratórios, de severidade variável, entre os dias 3 e 13 pi. Esses sinais consistiram de secreção nasal serosa à mucopurulenta e dificuldade respiratória leve à grave, além de secreção ocular. Além disso, esses animais apresentaram ganho de peso inferior aos grupos controle (G1) e ao grupo tratado com GCV (G3) nos dias 4, 6, 10, 12 e 14 pi (p<0,05). Um coelho deste grupo apresentou sinais neurológicos e morreu no dia 3 pós inoculação (pi). A presença do vírus no pulmão deste animal foi confirmada pelo isolamento viral e achados de histopatologia. Ao contrário, os animais do grupo G3 (inoculados com o EHV-1 e tratados com GCV) não apresentaram sinais sistêmicos e apresentaram apenas secreção nasal serosa leve. O ganho de peso desses animais foi semelhante aos animais do grupo controle (G1) e superior aos do grupo G2 nos dias 4, 6, 10, 12 e 14 pi (p<0,05). Excreção viral em secreções e soroconversão ao EHV-1 foram observados tanto nos animais do G2 quanto do G3, sem diferenças evidentes em magnitude e duração. Assim, o tratamento com GCV nos coelhos infectados com o EHV-1 (G3) resultou em manutenção do ganho diário de peso, abolição dos sinais sistêmicos e atenuação importante dos sinais clínicos respiratórios. Esses resultados são promissores no sentido da utilização do GCV no tratamento de infecções herpéticas em equinos. Não obstante, estudos mais aprofundados investigando-se diferentes doses, frequência de administração e atividade quando administrado após início dos sinais clínicos são necessários antes de sua utilização nessa espécie.Universidade Federal de Santa MariaBrasilMedicina VeterináriaUFSMPrograma de Pós-Graduação em Medicina VeterináriaCentro de Ciências RuraisFlores, Eduardo Furtadohttp://lattes.cnpq.br/0446078331070694Cargnelutti, Juliana FelipettoXXXXXXXXXXXXXXXXXXXXWeiblen, RudiXXXXXXXXXXXXXXXWeiss, MarceloXXXXXXXXXXXXXXXXXXMortari, Ana Paula Gnocato2021-05-18T17:34:52Z2021-05-18T17:34:52Z2019-02-27info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://repositorio.ufsm.br/handle/1/20918porAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessreponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSM2021-05-19T06:02:11Zoai:repositorio.ufsm.br:1/20918Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2021-05-19T06:02:11Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.none.fl_str_mv |
Atividade do ganciclovir em coelhos inoculados com o alfaherpesvírus equino 1 Activity of ganciclovir in rabbits inoclulated with equid alphaherpesvirus 1 |
title |
Atividade do ganciclovir em coelhos inoculados com o alfaherpesvírus equino 1 |
spellingShingle |
Atividade do ganciclovir em coelhos inoculados com o alfaherpesvírus equino 1 Mortari, Ana Paula Gnocato Alfaherpesvírus EHV-1 Terapia Ganciclovir Modelo animal Alphaherpesvirus Therapy Ganciclovir Animal model CNPQ::CIENCIAS AGRARIAS::MEDICINA VETERINARIA |
title_short |
Atividade do ganciclovir em coelhos inoculados com o alfaherpesvírus equino 1 |
title_full |
Atividade do ganciclovir em coelhos inoculados com o alfaherpesvírus equino 1 |
title_fullStr |
Atividade do ganciclovir em coelhos inoculados com o alfaherpesvírus equino 1 |
title_full_unstemmed |
Atividade do ganciclovir em coelhos inoculados com o alfaherpesvírus equino 1 |
title_sort |
Atividade do ganciclovir em coelhos inoculados com o alfaherpesvírus equino 1 |
author |
Mortari, Ana Paula Gnocato |
author_facet |
Mortari, Ana Paula Gnocato |
author_role |
author |
dc.contributor.none.fl_str_mv |
Flores, Eduardo Furtado http://lattes.cnpq.br/0446078331070694 Cargnelutti, Juliana Felipetto XXXXXXXXXXXXXXXXXXXX Weiblen, Rudi XXXXXXXXXXXXXXX Weiss, Marcelo XXXXXXXXXXXXXXXXXX |
dc.contributor.author.fl_str_mv |
Mortari, Ana Paula Gnocato |
dc.subject.por.fl_str_mv |
Alfaherpesvírus EHV-1 Terapia Ganciclovir Modelo animal Alphaherpesvirus Therapy Ganciclovir Animal model CNPQ::CIENCIAS AGRARIAS::MEDICINA VETERINARIA |
topic |
Alfaherpesvírus EHV-1 Terapia Ganciclovir Modelo animal Alphaherpesvirus Therapy Ganciclovir Animal model CNPQ::CIENCIAS AGRARIAS::MEDICINA VETERINARIA |
description |
Equine alfaherpervirus 1 (EHV-1), a member of the family Herpesviridae and subfamily Alphaherpesvirinae, is distributed worldwide and associated with abortions, respiratory and neurological disease in horses. No specific treatment for diseases associated with EHV-1 in horses is available, since human anti-herpetic drugs are not yet routinely used in equine medicine. Thus, the objective of this study was to investigate the in vivo anti-herpetic activity of ganciclovir (GCV), a nucleoside analogue drug used in the herpesvirus infections treatment in humans, against EHV-1. In vivo tests were performed in rabbits, an experimental model for EHV-1 respiratory disease. For this, eighteen New Zealand rabbits with approximately 30 days of age were alocated into three groups of 6 animals each and each group received a treatment: (G1) inoculated by the intranasal route (IN) with RPMI medium; (G2) inoculated by the IN route with 107 DICC50 of EHV-1 strain Kentucky D and (G3) inoculated with EHV-1 and treated with GCV (intravenously with 2.5mg / kg every 12h for 7 days). After inoculation, the animals were monitored for clinical, virological and pathological aspects for 15 days. All animals of G2 developed systemic signs (apathy, inappetence) and respiratory signs of variable severity between days 3 and 13 pi. These signs consisted of serous to mucopurulent nasal secretion and mild to severe respiratory distress, as well as ocular secretion. In addition, these animals presented lower weight gain than the control (G1) and GCV (G3) groups at days 4, 6, 10, 12 and 14 pi (p <0.05). A rabbit from this group presented neurological signs and died on day three after inoculation (pi). The presence of the virus in the lung of this animal was confirmed by viral isolation and histopathology. In contrast, animals from the G3 group (inoculated with EHV-1 and treated with GCV) showed no systemic signs and presented only mild serous nasal secretion. The weight gain of these animals was similar to those of the control group (G1) and higher than those of the G2 group at days 4, 6, 10, 12 and 14 pi (p <0.05). Viral excretion in secretions and seroconversion to EHV-1 were observed in both G2 and G3 animals, with no evident differences in magnitude and duration. Thus, GCV treatment in rabbits infected with EHV-1 (G3) resulted in maintenance of daily weight gain, abolition of systemic signs and significant attenuation of respiratory clinical signs. These results are promising for the use of GCV in the treatment of herpes infections in horses. However, further studies investigating different doses, frequency of administration and activity when administered after the onset of clinical signs are necessary prior to its use in this species. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019-02-27 2021-05-18T17:34:52Z 2021-05-18T17:34:52Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/20918 |
url |
http://repositorio.ufsm.br/handle/1/20918 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.rights.driver.fl_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Brasil Medicina Veterinária UFSM Programa de Pós-Graduação em Medicina Veterinária Centro de Ciências Rurais |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Brasil Medicina Veterinária UFSM Programa de Pós-Graduação em Medicina Veterinária Centro de Ciências Rurais |
dc.source.none.fl_str_mv |
reponame:Manancial - Repositório Digital da UFSM instname:Universidade Federal de Santa Maria (UFSM) instacron:UFSM |
instname_str |
Universidade Federal de Santa Maria (UFSM) |
instacron_str |
UFSM |
institution |
UFSM |
reponame_str |
Manancial - Repositório Digital da UFSM |
collection |
Manancial - Repositório Digital da UFSM |
repository.name.fl_str_mv |
Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM) |
repository.mail.fl_str_mv |
atendimento.sib@ufsm.br||tedebc@gmail.com |
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1805922088865759232 |