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  • Forsgård, Richard A.,1987-Pharmacology, Faculty of Medicine, University of Helsinki, Helsinki, Finland (författare)

Chemotherapy-induced gastrointestinal toxicity is associated with changes in serum and urine metabolome and fecal microbiota in male Sprague-Dawley rats

  • Artikel/kapitelEngelska2017

Förlag, utgivningsår, omfång ...

  • 2017-06-23
  • Springer,2017
  • printrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:oru-83107
  • https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-83107URI
  • https://doi.org/10.1007/s00280-017-3364-zDOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:136321276URI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • Funding Agencies:Cancer Society of Finland  Finska Läkaresällskapet  Foundation of Clinical Chemistry Research  Biomedicum Helsinki Foundation  Ministry of Economy and Competitiveness of Spain SAF2014-52875RInstituto de Salud Carlos IIIEuropean Union (EU) PIE15/00013
  • Purpose: Chemotherapy-induced gastrointestinal toxicity (CIGT) is a complex process that involves multiple pathophysiological mechanisms. We have previously shown that commonly used chemotherapeutics 5-fluorouracil, oxaliplatin, and irinotecan damage the intestinal mucosa and increase intestinal permeability to iohexol. We hypothesized that CIGT is associated with alterations in fecal microbiota and metabolome. Our aim was to characterize these changes and examine how they relate to the severity of CIGT.Methods: A total of 48 male Sprague-Dawley rats were injected intraperitoneally either with 5-fluorouracil (150 mg/kg), oxaliplatin (15 mg/kg), or irinotecan (200 mg/kg). Body weight change was measured daily after drug administration and the animals were euthanized after 72 h. Blood, urine, and fecal samples were collected at baseline and at the end of the experiment. The changes in the composition of fecal microbiota were analyzed with 16S rRNA gene sequencing. Metabolic changes in serum and urine metabolome were measured with 1 mm proton nuclear magnetic resonance (1H-NMR).Results: Irinotecan increased the relative abundance of Fusobacteria and Proteobacteria, while 5-FU and oxaliplatin caused only minor changes in the composition of fecal microbiota. All chemotherapeutics increased the levels of serum fatty acids and N(CH3)(3) moieties and decreased the levels of Krebs cycle metabolites and free amino acids.Conclusions: Chemotherapeutic drugs, 5-fluorouracil, oxaliplatin, and irinotecan, induce several microbial and metabolic changes which may play a role in the pathophysiology of CIGT. The observed changes in intestinal permeability, fecal microbiota, and metabolome suggest the activation of inflammatory processes.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Marrachelli, Vannina G.Metabolomics and Molecular Imaging Lab, Health Research Institute INCLIVA, Valencia, Spain (författare)
  • Korpela, KatriImmunobiology Research Program, Department of Bacteriology and Immunology, University of Helsinki, Helsinki, Finland (författare)
  • Frias, RafaelKarolinska Institutet (författare)
  • Carmen Collado, MariaInstitute of Agrochemistry and Food Technology, National Research Council (IATA-CSIC), Valencia, Spain (författare)
  • Korpela, RiittaPharmacology, Faculty of Medicine, University of Helsinki, Helsinki, Finland (författare)
  • Monleon, DanielMetabolomics and Molecular Imaging Lab, Health Research Institute INCLIVA, Valencia, Spain (författare)
  • Spillmann, ThomasDepartment of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland (författare)
  • Österlund, PiaDepartment of Oncology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Department of Oncology, Tampere University Hospital, Tampere, Finland (författare)
  • Pharmacology, Faculty of Medicine, University of Helsinki, Helsinki, FinlandMetabolomics and Molecular Imaging Lab, Health Research Institute INCLIVA, Valencia, Spain (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Cancer Chemotherapy and Pharmacology: Springer80:2, s. 317-3320344-57041432-0843

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