Evidence map›Paper›PMID 37685929›Full record

ArticleInternational journal of molecular sciences2023

A Clinically Relevant Dosage of Mitoxantrone Disrupts the Glutathione and Lipid Metabolic Pathways of the CD-1 Mice Brain: A Metabolomics Study.

Ana Dias-Carvalho, Ana Margarida-Araújo, Ana Reis-Mendes, Catarina Oliveira Sequeira, Sofia Azeredo Pereira, Paula Guedes de Pinho, Félix Carvalho, Susana Isabel Sá, Eduarda Fernandes, Vera Marisa Costa

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
2.1field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 8 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 1 country.

Ana Dias-CarvalhoAssociate Laboratory i4HB, Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal.
Ana Margarida-AraújoAssociate Laboratory i4HB, Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal.ORCID 0000-0002-4073-2121
Ana Reis-MendesAssociate Laboratory i4HB, Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal.ORCID 0000-0002-2775-3147
Catarina Oliveira SequeiraiNOVA4Health, LS4Future, NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM), Universidade Nova de Lisboa, 1150-082 Lisboa, Portugal.
Sofia Azeredo PereiraiNOVA4Health, LS4Future, NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM), Universidade Nova de Lisboa, 1150-082 Lisboa, Portugal.ORCID 0000-0002-8456-9995
Paula Guedes de PinhoAssociate Laboratory i4HB, Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal.ORCID 0000-0002-7395-5700
Félix CarvalhoAssociate Laboratory i4HB, Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal.
Susana Isabel SáUnit of Anatomy, Department of Biomedicine, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal.ORCID 0000-0002-5078-980X
Eduarda FernandesLAQV-REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal.ORCID 0000-0001-6424-0976
Vera Marisa CostaAssociate Laboratory i4HB, Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal.ORCID 0000-0002-0471-2756
Universidade do Porto · PTUniversidade Nova de Lisboa · PT

Funding

Fundação para a Ciência e Tecnologia DL57/2016/CP1334/CT0006Fundação para a Ciência e Tecnologia UIDP/04378/2020 and UIDB/04378/2020
6 · The paper itself

Abstract

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.

Indexed as

Chemotherapy-Related Cognitive ImpairmentMitoxantroneAnimalsBrainGlutathioneLipidsMaleMetabolic Networks and PathwaysMetabolomicsMiceGlutathioneLipidsMitoxantroneadverse outcome pathwayscancerchemotherapymetabolomics approachmultiple sclerosistopoisomerase inhibitors

Identifiers

PMID37685929
PMCPMC10488007
OpenAlexW4386099349

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.