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Chemotherapy-induce...
Chemotherapy-induced gastrointestinal toxicity is associated with changes in serum and urine metabolome and fecal microbiota in male Sprague-Dawley rats
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- Forsgård, Richard A., 1987- (author)
- Pharmacology, Faculty of Medicine, University of Helsinki, Helsinki, Finland
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- Marrachelli, Vannina G. (author)
- Metabolomics and Molecular Imaging Lab, Health Research Institute INCLIVA, Valencia, Spain
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- Korpela, Katri (author)
- Immunobiology Research Program, Department of Bacteriology and Immunology, University of Helsinki, Helsinki, Finland
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- Frias, Rafael (author)
- Karolinska Institutet
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- Carmen Collado, Maria (author)
- Institute of Agrochemistry and Food Technology, National Research Council (IATA-CSIC), Valencia, Spain
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- Korpela, Riitta (author)
- Pharmacology, Faculty of Medicine, University of Helsinki, Helsinki, Finland
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- Monleon, Daniel (author)
- Metabolomics and Molecular Imaging Lab, Health Research Institute INCLIVA, Valencia, Spain
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- Spillmann, Thomas (author)
- Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland
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- Österlund, Pia (author)
- Department of Oncology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Department of Oncology, Tampere University Hospital, Tampere, Finland
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(creator_code:org_t)
- 2017-06-23
- 2017
- English.
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In: Cancer Chemotherapy and Pharmacology. - : Springer. - 0344-5704 .- 1432-0843. ; 80:2, s. 317-332
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Abstract
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
Keyword
- Chemotherapy
- Metabolomics
- Microbiota
- 5-FU
- Oxaliplatin
- Irinotecan
Publication and Content Type
- ref (subject category)
- art (subject category)
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