Cumulative Mitoxantrone-Induced Haematological and Hepatic Adverse Effects in a Subchronic In vivo Study
Autor(a) principal: | |
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Data de Publicação: | 2014 |
Outros Autores: | , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10316/25490 https://doi.org/10.1111/bcpt.12143 |
Resumo: | Mitoxantrone (MTX) is an antineoplastic agent that can induce hepato- and haematotoxicity. This work aimed to investigate the occurrence of cumulative early and late MTX-induced hepatic and haematological disturbances in an vivo model. A control group and two groups treated with three cycles of 2.5 mg/kg MTX at days 0, 10 and 20 were formed. One of the treated groups suffered euthanasia on day 22 (MTX22) to evaluate early MTX toxic effects, while the other suffered euthanasia on day 48 (MTX48), to allow the evaluation of MTX late effects. An early immunosuppression with a drop in the IgG levels was observed, causing a slight decrease in the plasma total protein content. The early bone marrow depression was followed by signs of recovery in MTX48. The genotoxic potential of MTX was demonstrated by the presence of several micronuclei in MTX22 leucocytes. Increases in plasma iron and cholesterol levels in the MTX22 rats were observed, while in both groups increases in the unconjugated bilirubin, C4 complement, and decreases in the triglycerides, alanine aminotransferase, alkaline phosphatase and transferrin were found in plasma samples. On MTX 48, the liver histology showed more hepatotoxic signs, the hepatic levels of reduced and oxidized glutathione were increased, and ATP hepatic levels were decreased. However, the hepatic total protein levels were decreased only in the livers of MTX22 group. Results demonstrated the MTX genotoxic effects, haemato- and direct hepatotoxicity. While the haematological toxicity is ameliorated with time, the same was not observed in the hepatic injury. |
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Cumulative Mitoxantrone-Induced Haematological and Hepatic Adverse Effects in a Subchronic In vivo StudyMULTIPLE-SCLEROSISPROTEIN-SYNTHESISLIVERHEPATOTOXICITYCELLSTOXICITYPHARMACOKINETICSCARDIOTOXICITYCHEMOTHERAPYINHIBITIONMitoxantrone (MTX) is an antineoplastic agent that can induce hepato- and haematotoxicity. This work aimed to investigate the occurrence of cumulative early and late MTX-induced hepatic and haematological disturbances in an vivo model. A control group and two groups treated with three cycles of 2.5 mg/kg MTX at days 0, 10 and 20 were formed. One of the treated groups suffered euthanasia on day 22 (MTX22) to evaluate early MTX toxic effects, while the other suffered euthanasia on day 48 (MTX48), to allow the evaluation of MTX late effects. An early immunosuppression with a drop in the IgG levels was observed, causing a slight decrease in the plasma total protein content. The early bone marrow depression was followed by signs of recovery in MTX48. The genotoxic potential of MTX was demonstrated by the presence of several micronuclei in MTX22 leucocytes. Increases in plasma iron and cholesterol levels in the MTX22 rats were observed, while in both groups increases in the unconjugated bilirubin, C4 complement, and decreases in the triglycerides, alanine aminotransferase, alkaline phosphatase and transferrin were found in plasma samples. On MTX 48, the liver histology showed more hepatotoxic signs, the hepatic levels of reduced and oxidized glutathione were increased, and ATP hepatic levels were decreased. However, the hepatic total protein levels were decreased only in the livers of MTX22 group. Results demonstrated the MTX genotoxic effects, haemato- and direct hepatotoxicity. While the haematological toxicity is ameliorated with time, the same was not observed in the hepatic injury.This work was supported by the Fundação para a Ciencia e Tecnologia (FCT) - project (EXPL/DTP-FTO/0290/2012) - QREN initiative with EU/FEDER financing through COMPETE - Operational Programme for Competitiveness Factors. The work was also supported by FCT within the framework of Strategic Projects for Scientific Research Units of R&D (project PEst-C/EQB/LA0006/2011). LGR, VMC and RJD-O thank FCT for their PhD grant (SFRH/BD/63473/2009) and Post-doc grants (SFRH/BPD/63746/2009) and (SFRH/BPD/ 36865/2007), respectively. MDA thanks Capes Foundation (Brazil) for his PhD Grant (BEX 0593/10-9).Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society)2014info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/25490http://hdl.handle.net/10316/25490https://doi.org/10.1111/bcpt.12143enghttp://onlinelibrary.wiley.com/doi/10.1111/bcpt.12143/abstractRossato, Luciana G.Costa, Vera M.Dallegrave, ElianeArbo, MarceloDinis-Oliveira, Ricardo J.Santos-Silva, AliceDuarte, José A.Bastos, Maria de LourdesPalmeira, C. M.Remião, Fernandoinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2021-10-20T15:23:53Zoai:estudogeral.uc.pt:10316/25490Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:56:00.681708Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Cumulative Mitoxantrone-Induced Haematological and Hepatic Adverse Effects in a Subchronic In vivo Study |
title |
Cumulative Mitoxantrone-Induced Haematological and Hepatic Adverse Effects in a Subchronic In vivo Study |
spellingShingle |
Cumulative Mitoxantrone-Induced Haematological and Hepatic Adverse Effects in a Subchronic In vivo Study Rossato, Luciana G. MULTIPLE-SCLEROSIS PROTEIN-SYNTHESIS LIVER HEPATOTOXICITY CELLS TOXICITY PHARMACOKINETICS CARDIOTOXICITY CHEMOTHERAPY INHIBITION |
title_short |
Cumulative Mitoxantrone-Induced Haematological and Hepatic Adverse Effects in a Subchronic In vivo Study |
title_full |
Cumulative Mitoxantrone-Induced Haematological and Hepatic Adverse Effects in a Subchronic In vivo Study |
title_fullStr |
Cumulative Mitoxantrone-Induced Haematological and Hepatic Adverse Effects in a Subchronic In vivo Study |
title_full_unstemmed |
Cumulative Mitoxantrone-Induced Haematological and Hepatic Adverse Effects in a Subchronic In vivo Study |
title_sort |
Cumulative Mitoxantrone-Induced Haematological and Hepatic Adverse Effects in a Subchronic In vivo Study |
author |
Rossato, Luciana G. |
author_facet |
Rossato, Luciana G. Costa, Vera M. Dallegrave, Eliane Arbo, Marcelo Dinis-Oliveira, Ricardo J. Santos-Silva, Alice Duarte, José A. Bastos, Maria de Lourdes Palmeira, C. M. Remião, Fernando |
author_role |
author |
author2 |
Costa, Vera M. Dallegrave, Eliane Arbo, Marcelo Dinis-Oliveira, Ricardo J. Santos-Silva, Alice Duarte, José A. Bastos, Maria de Lourdes Palmeira, C. M. Remião, Fernando |
author2_role |
author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Rossato, Luciana G. Costa, Vera M. Dallegrave, Eliane Arbo, Marcelo Dinis-Oliveira, Ricardo J. Santos-Silva, Alice Duarte, José A. Bastos, Maria de Lourdes Palmeira, C. M. Remião, Fernando |
dc.subject.por.fl_str_mv |
MULTIPLE-SCLEROSIS PROTEIN-SYNTHESIS LIVER HEPATOTOXICITY CELLS TOXICITY PHARMACOKINETICS CARDIOTOXICITY CHEMOTHERAPY INHIBITION |
topic |
MULTIPLE-SCLEROSIS PROTEIN-SYNTHESIS LIVER HEPATOTOXICITY CELLS TOXICITY PHARMACOKINETICS CARDIOTOXICITY CHEMOTHERAPY INHIBITION |
description |
Mitoxantrone (MTX) is an antineoplastic agent that can induce hepato- and haematotoxicity. This work aimed to investigate the occurrence of cumulative early and late MTX-induced hepatic and haematological disturbances in an vivo model. A control group and two groups treated with three cycles of 2.5 mg/kg MTX at days 0, 10 and 20 were formed. One of the treated groups suffered euthanasia on day 22 (MTX22) to evaluate early MTX toxic effects, while the other suffered euthanasia on day 48 (MTX48), to allow the evaluation of MTX late effects. An early immunosuppression with a drop in the IgG levels was observed, causing a slight decrease in the plasma total protein content. The early bone marrow depression was followed by signs of recovery in MTX48. The genotoxic potential of MTX was demonstrated by the presence of several micronuclei in MTX22 leucocytes. Increases in plasma iron and cholesterol levels in the MTX22 rats were observed, while in both groups increases in the unconjugated bilirubin, C4 complement, and decreases in the triglycerides, alanine aminotransferase, alkaline phosphatase and transferrin were found in plasma samples. On MTX 48, the liver histology showed more hepatotoxic signs, the hepatic levels of reduced and oxidized glutathione were increased, and ATP hepatic levels were decreased. However, the hepatic total protein levels were decreased only in the livers of MTX22 group. Results demonstrated the MTX genotoxic effects, haemato- and direct hepatotoxicity. While the haematological toxicity is ameliorated with time, the same was not observed in the hepatic injury. |
publishDate |
2014 |
dc.date.none.fl_str_mv |
2014 |
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://hdl.handle.net/10316/25490 http://hdl.handle.net/10316/25490 https://doi.org/10.1111/bcpt.12143 |
url |
http://hdl.handle.net/10316/25490 https://doi.org/10.1111/bcpt.12143 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
http://onlinelibrary.wiley.com/doi/10.1111/bcpt.12143/abstract |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society) |
publisher.none.fl_str_mv |
Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society) |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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