Toxicity of a methotrexate metronomic schedule in Wistar rats
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1016/j.rvsc.2020.07.015 http://hdl.handle.net/11449/201984 |
Resumo: | Metronomic chemotherapy is a relevant strategy that uses low doses of antineoplastic drugs for sustained periods to control tumor growth, an alternative frequently utilized in veterinary patients. This work aimed to evaluate the toxic effects of a metronomic oral dose of methotrexate (MTX) for 45 days in tumor-free Wistar rats when compared with control animals. Clinical alterations, body weight, food, and water intake were monitored daily, and bone marrow suppression, hematological, biochemical, and histopathological analyses were performed at three points (days 30, 45, and 60). MTX-treated animals did not demonstrate severe systemic involvement. At 30 days, compared with control animals, MTX-treated animals showed significant leukocytosis (11.9 ± 2.3 vs. 7.8 ± 0.2 106/μL; P <.05) and augmentation of immature myeloid populations from bone marrow (9.0 ± 0.8 vs. 6.5 ± 1.5%; P <.05), and at 60 days, treated animals showed significant neutrophilia (35.0 ± 11.0 vs. 23.00 ± 3.0%; P <.05), depletion of bone marrow lymphocytes (8.2 ± 0.7 vs. 11.5 ± 1.9%; P <.05), and immature myeloid populations (7.2 ± 0.7 vs. 8.3 ± 0.6%; P <.05). At a histopathological level, splenic hypoplasia and respiratory inflammatory lesions were significant when compared with control animals, presenting mild to moderate myelotoxicity, immune suppression, and associated clinical compromise that persisted beyond treatment withdrawal. This suggested that MTX metronomic toxicity should not be neglected owing to the observed residual side-effects and special care should be taken regarding myelosuppression. |
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Toxicity of a methotrexate metronomic schedule in Wistar ratsAnimalsAnti-folateCancerChemotherapyMetronomicMetronomic chemotherapy is a relevant strategy that uses low doses of antineoplastic drugs for sustained periods to control tumor growth, an alternative frequently utilized in veterinary patients. This work aimed to evaluate the toxic effects of a metronomic oral dose of methotrexate (MTX) for 45 days in tumor-free Wistar rats when compared with control animals. Clinical alterations, body weight, food, and water intake were monitored daily, and bone marrow suppression, hematological, biochemical, and histopathological analyses were performed at three points (days 30, 45, and 60). MTX-treated animals did not demonstrate severe systemic involvement. At 30 days, compared with control animals, MTX-treated animals showed significant leukocytosis (11.9 ± 2.3 vs. 7.8 ± 0.2 106/μL; P <.05) and augmentation of immature myeloid populations from bone marrow (9.0 ± 0.8 vs. 6.5 ± 1.5%; P <.05), and at 60 days, treated animals showed significant neutrophilia (35.0 ± 11.0 vs. 23.00 ± 3.0%; P <.05), depletion of bone marrow lymphocytes (8.2 ± 0.7 vs. 11.5 ± 1.9%; P <.05), and immature myeloid populations (7.2 ± 0.7 vs. 8.3 ± 0.6%; P <.05). At a histopathological level, splenic hypoplasia and respiratory inflammatory lesions were significant when compared with control animals, presenting mild to moderate myelotoxicity, immune suppression, and associated clinical compromise that persisted beyond treatment withdrawal. This suggested that MTX metronomic toxicity should not be neglected owing to the observed residual side-effects and special care should be taken regarding myelosuppression.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Department of Veterinary Clinic and Surgery School of Agricultural and Veterinarian Sciences São Paulo State University (Unesp), Via de Acesso Prof. Paulo Donato Castellane s/nDepartment of Veterinary Pathology School of Agricultural and Veterinarian Sciences São Paulo State University (Unesp), Via de Acesso Prof. Paulo Donato Castellane s/nDepartment of Veterinary Clinic and Surgery School of Agricultural and Veterinarian Sciences São Paulo State University (Unesp), Via de Acesso Prof. Paulo Donato Castellane s/nDepartment of Veterinary Pathology School of Agricultural and Veterinarian Sciences São Paulo State University (Unesp), Via de Acesso Prof. Paulo Donato Castellane s/nCNPq: 304468/2013-4Universidade Estadual Paulista (Unesp)Correal, María Lucía [UNESP]Camplesi, Annelise Carla [UNESP]Anai, Letícia Abrahão [UNESP]Bertolo, Paulo Henrique Leal [UNESP]Vasconcelos, Rosemeri de Oliveira [UNESP]Santana, Áureo Evangelista [UNESP]2020-12-12T02:46:53Z2020-12-12T02:46:53Z2020-10-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article379-385http://dx.doi.org/10.1016/j.rvsc.2020.07.015Research in Veterinary Science, v. 132, p. 379-385.1532-26610034-5288http://hdl.handle.net/11449/20198410.1016/j.rvsc.2020.07.0152-s2.0-85088863941Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengResearch in Veterinary Scienceinfo:eu-repo/semantics/openAccess2021-10-23T04:16:11Zoai:repositorio.unesp.br:11449/201984Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462021-10-23T04:16:11Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Toxicity of a methotrexate metronomic schedule in Wistar rats |
title |
Toxicity of a methotrexate metronomic schedule in Wistar rats |
spellingShingle |
Toxicity of a methotrexate metronomic schedule in Wistar rats Correal, María Lucía [UNESP] Animals Anti-folate Cancer Chemotherapy Metronomic |
title_short |
Toxicity of a methotrexate metronomic schedule in Wistar rats |
title_full |
Toxicity of a methotrexate metronomic schedule in Wistar rats |
title_fullStr |
Toxicity of a methotrexate metronomic schedule in Wistar rats |
title_full_unstemmed |
Toxicity of a methotrexate metronomic schedule in Wistar rats |
title_sort |
Toxicity of a methotrexate metronomic schedule in Wistar rats |
author |
Correal, María Lucía [UNESP] |
author_facet |
Correal, María Lucía [UNESP] Camplesi, Annelise Carla [UNESP] Anai, Letícia Abrahão [UNESP] Bertolo, Paulo Henrique Leal [UNESP] Vasconcelos, Rosemeri de Oliveira [UNESP] Santana, Áureo Evangelista [UNESP] |
author_role |
author |
author2 |
Camplesi, Annelise Carla [UNESP] Anai, Letícia Abrahão [UNESP] Bertolo, Paulo Henrique Leal [UNESP] Vasconcelos, Rosemeri de Oliveira [UNESP] Santana, Áureo Evangelista [UNESP] |
author2_role |
author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (Unesp) |
dc.contributor.author.fl_str_mv |
Correal, María Lucía [UNESP] Camplesi, Annelise Carla [UNESP] Anai, Letícia Abrahão [UNESP] Bertolo, Paulo Henrique Leal [UNESP] Vasconcelos, Rosemeri de Oliveira [UNESP] Santana, Áureo Evangelista [UNESP] |
dc.subject.por.fl_str_mv |
Animals Anti-folate Cancer Chemotherapy Metronomic |
topic |
Animals Anti-folate Cancer Chemotherapy Metronomic |
description |
Metronomic chemotherapy is a relevant strategy that uses low doses of antineoplastic drugs for sustained periods to control tumor growth, an alternative frequently utilized in veterinary patients. This work aimed to evaluate the toxic effects of a metronomic oral dose of methotrexate (MTX) for 45 days in tumor-free Wistar rats when compared with control animals. Clinical alterations, body weight, food, and water intake were monitored daily, and bone marrow suppression, hematological, biochemical, and histopathological analyses were performed at three points (days 30, 45, and 60). MTX-treated animals did not demonstrate severe systemic involvement. At 30 days, compared with control animals, MTX-treated animals showed significant leukocytosis (11.9 ± 2.3 vs. 7.8 ± 0.2 106/μL; P <.05) and augmentation of immature myeloid populations from bone marrow (9.0 ± 0.8 vs. 6.5 ± 1.5%; P <.05), and at 60 days, treated animals showed significant neutrophilia (35.0 ± 11.0 vs. 23.00 ± 3.0%; P <.05), depletion of bone marrow lymphocytes (8.2 ± 0.7 vs. 11.5 ± 1.9%; P <.05), and immature myeloid populations (7.2 ± 0.7 vs. 8.3 ± 0.6%; P <.05). At a histopathological level, splenic hypoplasia and respiratory inflammatory lesions were significant when compared with control animals, presenting mild to moderate myelotoxicity, immune suppression, and associated clinical compromise that persisted beyond treatment withdrawal. This suggested that MTX metronomic toxicity should not be neglected owing to the observed residual side-effects and special care should be taken regarding myelosuppression. |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020-12-12T02:46:53Z 2020-12-12T02:46:53Z 2020-10-01 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1016/j.rvsc.2020.07.015 Research in Veterinary Science, v. 132, p. 379-385. 1532-2661 0034-5288 http://hdl.handle.net/11449/201984 10.1016/j.rvsc.2020.07.015 2-s2.0-85088863941 |
url |
http://dx.doi.org/10.1016/j.rvsc.2020.07.015 http://hdl.handle.net/11449/201984 |
identifier_str_mv |
Research in Veterinary Science, v. 132, p. 379-385. 1532-2661 0034-5288 10.1016/j.rvsc.2020.07.015 2-s2.0-85088863941 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Research in Veterinary Science |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
379-385 |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
_version_ |
1797789537595817984 |