A Clinically Relevant Dosage of Mitoxantrone Disrupts the Glutathione and Lipid Metabolic Pathways of the CD-1 Mice Brain
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2023 |
| 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/10362/158255 |
Resumo: | Funding Information: This work is financed by national funds from Fundação para a Ciência e a Tecnologia (FCT), I.P., in the scope of the project UIDP/04378/2020 and UIDB/04378/2020 of the Research Unit on Applied Molecular Biosciences (UCIBIO) and the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy—i4HB and through the project EXPL/MEDFAR/0203/2021. A. Dias-Carvalho acknowledges FCT and UCIBIO for her PhD grant (UI/BD/151318/2021). V.M.C acknowledges FCT for her grant (SFRH/BPD/110001/2015) that was funded by national funds through FCT under the Norma Transitória–DL57/2016/CP1334/CT0006. A.R.-M. acknowledges FCT for her grant SFRH/BD/129359/2017. Publisher Copyright: © 2023 by the authors. |
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A Clinically Relevant Dosage of Mitoxantrone Disrupts the Glutathione and Lipid Metabolic Pathways of the CD-1 Mice BrainA Metabolomics Studyadverse outcome pathwayscancerchemotherapymetabolomics approachmultiple sclerosistopoisomerase inhibitorsCatalysisMolecular BiologySpectroscopyComputer Science ApplicationsPhysical and Theoretical ChemistryOrganic ChemistryInorganic ChemistrySDG 3 - Good Health and Well-beingFunding Information: This work is financed by national funds from Fundação para a Ciência e a Tecnologia (FCT), I.P., in the scope of the project UIDP/04378/2020 and UIDB/04378/2020 of the Research Unit on Applied Molecular Biosciences (UCIBIO) and the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy—i4HB and through the project EXPL/MEDFAR/0203/2021. A. Dias-Carvalho acknowledges FCT and UCIBIO for her PhD grant (UI/BD/151318/2021). V.M.C acknowledges FCT for her grant (SFRH/BPD/110001/2015) that was funded by national funds through FCT under the Norma Transitória–DL57/2016/CP1334/CT0006. A.R.-M. acknowledges FCT for her grant SFRH/BD/129359/2017. Publisher Copyright: © 2023 by the authors.Long-term cognitive dysfunction, or “chemobrain”, has been observed in cancer patients treated with chemotherapy. Mitoxantrone (MTX) is a topoisomerase II inhibitor that binds and intercalates with DNA, being used in the treatment of several cancers and multiple sclerosis. Although MTX can induce chemobrain, its neurotoxic mechanisms are poorly studied. This work aimed to identify the adverse outcome pathways (AOPs) activated in the brain upon the use of a clinically relevant cumulative dose of MTX. Three-month-old male CD-1 mice were given a biweekly intraperitoneal administration of MTX over the course of three weeks until reaching a total cumulative dose of 6 mg/kg. Controls were given sterile saline in the same schedule. Two weeks after the last administration, the mice were euthanized and their brains removed. The left brain hemisphere was used for targeted profiling of the metabolism of glutathione and the right hemisphere for an untargeted metabolomics approach. The obtained results revealed that MTX treatment reduced the availability of cysteine (Cys), cysteinylglycine (CysGly), and reduced glutathione (GSH) suggesting that MTX disrupts glutathione metabolism. The untargeted approach revealed metabolic circuits of phosphatidylethanolamine, catecholamines, unsaturated fatty acids biosynthesis, and glycerolipids as relevant players in AOPs of MTX in our in vivo model. As far as we know, our study was the first to perform such a broad profiling study on pathways that could put patients given MTX at risk of cognitive deficits.iNOVA4Health - pólo NMSNOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)RUNDias-Carvalho, AnaMargarida-Araújo, AnaReis-Mendes, AnaSequeira, Catarina OliveiraPereira, Sofia AzeredoGuedes de Pinho, PaulaCarvalho, FélixSá, Susana IsabelFernandes, EduardaCosta, Vera Marisa2023-09-25T22:18:58Z2023-092023-09-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/158255eng1661-6596PURE: 71606192https://doi.org/10.3390/ijms241713126info: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:RCAAP2024-03-11T05:40:29Zoai:run.unl.pt:10362/158255Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:57:01.999933Repositório 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 |
A Clinically Relevant Dosage of Mitoxantrone Disrupts the Glutathione and Lipid Metabolic Pathways of the CD-1 Mice Brain A Metabolomics Study |
| title |
A Clinically Relevant Dosage of Mitoxantrone Disrupts the Glutathione and Lipid Metabolic Pathways of the CD-1 Mice Brain |
| spellingShingle |
A Clinically Relevant Dosage of Mitoxantrone Disrupts the Glutathione and Lipid Metabolic Pathways of the CD-1 Mice Brain Dias-Carvalho, Ana adverse outcome pathways cancer chemotherapy metabolomics approach multiple sclerosis topoisomerase inhibitors Catalysis Molecular Biology Spectroscopy Computer Science Applications Physical and Theoretical Chemistry Organic Chemistry Inorganic Chemistry SDG 3 - Good Health and Well-being |
| title_short |
A Clinically Relevant Dosage of Mitoxantrone Disrupts the Glutathione and Lipid Metabolic Pathways of the CD-1 Mice Brain |
| title_full |
A Clinically Relevant Dosage of Mitoxantrone Disrupts the Glutathione and Lipid Metabolic Pathways of the CD-1 Mice Brain |
| title_fullStr |
A Clinically Relevant Dosage of Mitoxantrone Disrupts the Glutathione and Lipid Metabolic Pathways of the CD-1 Mice Brain |
| title_full_unstemmed |
A Clinically Relevant Dosage of Mitoxantrone Disrupts the Glutathione and Lipid Metabolic Pathways of the CD-1 Mice Brain |
| title_sort |
A Clinically Relevant Dosage of Mitoxantrone Disrupts the Glutathione and Lipid Metabolic Pathways of the CD-1 Mice Brain |
| author |
Dias-Carvalho, Ana |
| author_facet |
Dias-Carvalho, Ana Margarida-Araújo, Ana Reis-Mendes, Ana Sequeira, Catarina Oliveira Pereira, Sofia Azeredo Guedes de Pinho, Paula Carvalho, Félix Sá, Susana Isabel Fernandes, Eduarda Costa, Vera Marisa |
| author_role |
author |
| author2 |
Margarida-Araújo, Ana Reis-Mendes, Ana Sequeira, Catarina Oliveira Pereira, Sofia Azeredo Guedes de Pinho, Paula Carvalho, Félix Sá, Susana Isabel Fernandes, Eduarda Costa, Vera Marisa |
| author2_role |
author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
iNOVA4Health - pólo NMS NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM) RUN |
| dc.contributor.author.fl_str_mv |
Dias-Carvalho, Ana Margarida-Araújo, Ana Reis-Mendes, Ana Sequeira, Catarina Oliveira Pereira, Sofia Azeredo Guedes de Pinho, Paula Carvalho, Félix Sá, Susana Isabel Fernandes, Eduarda Costa, Vera Marisa |
| dc.subject.por.fl_str_mv |
adverse outcome pathways cancer chemotherapy metabolomics approach multiple sclerosis topoisomerase inhibitors Catalysis Molecular Biology Spectroscopy Computer Science Applications Physical and Theoretical Chemistry Organic Chemistry Inorganic Chemistry SDG 3 - Good Health and Well-being |
| topic |
adverse outcome pathways cancer chemotherapy metabolomics approach multiple sclerosis topoisomerase inhibitors Catalysis Molecular Biology Spectroscopy Computer Science Applications Physical and Theoretical Chemistry Organic Chemistry Inorganic Chemistry SDG 3 - Good Health and Well-being |
| description |
Funding Information: This work is financed by national funds from Fundação para a Ciência e a Tecnologia (FCT), I.P., in the scope of the project UIDP/04378/2020 and UIDB/04378/2020 of the Research Unit on Applied Molecular Biosciences (UCIBIO) and the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy—i4HB and through the project EXPL/MEDFAR/0203/2021. A. Dias-Carvalho acknowledges FCT and UCIBIO for her PhD grant (UI/BD/151318/2021). V.M.C acknowledges FCT for her grant (SFRH/BPD/110001/2015) that was funded by national funds through FCT under the Norma Transitória–DL57/2016/CP1334/CT0006. A.R.-M. acknowledges FCT for her grant SFRH/BD/129359/2017. Publisher Copyright: © 2023 by the authors. |
| publishDate |
2023 |
| dc.date.none.fl_str_mv |
2023-09-25T22:18:58Z 2023-09 2023-09-01T00:00:00Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
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http://hdl.handle.net/10362/158255 |
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http://hdl.handle.net/10362/158255 |
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eng |
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eng |
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1661-6596 PURE: 71606192 https://doi.org/10.3390/ijms241713126 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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