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Two-Week Aflibercept or Erlotinib Administration Does Not Induce Changes in Intestinal Morphology in Male Sprague-Dawley Rats But Aflibercept Affects Serum and Urine Metabolic Profiles
Pharmacology, Faculty of Medicine, University of Helsinki, Helsinki, Finland.ORCID iD: 0000-0002-1905-918x
Health research Institute INCLIVA, Metabolomics and Molecular Imaging Lab, Valencia, Spain; Department of Physiology, Faculty of Medicine, University of Valencia, Valencia, Spain.
FCLAP, Department of Veterinary Biosciences, Faculty of Veterinary Medicine, University of Helsinki, Finland.ORCID iD: 0000-0001-9872-3626
Comparative Medicine, Karolinska Institutet, Stockholm, Sweden.
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2019 (English)In: Translational Oncology, ISSN 1944-7124, E-ISSN 1936-5233, Vol. 12, no 8, p. 1122-1130Article in journal (Refereed) Published
Abstract [en]

Gastrointestinal toxicity is a frequently observed adverse event during cancer treatment with traditional chemotherapeutics. Currently, traditional chemotherapeutics are often combined with targeted biologic agents. These biologics, however, possess a distinct toxicity profile, and they may also exacerbate the adverse effects of traditional chemotherapeutics. In this study, we aimed to characterize the gastrointestinal and metabolic changes after a 2-week treatment period with aflibercept, an antiangiogenic VEGFR decoy, and with erlotinib, a tyrosine-kinase inhibitor. Male rats were treated either with aflibercept or erlotinib for 2 weeks. During the 2-week treatment period, the animals in the aflibercept group received twosubcutaneous doses of 25 mg/kg aflibercept. The erlotinib group got 10 mg/kg of erlotinib by oral gavage every other day. The control groups were treated similarly but received either saline injections or oral gavage of water. Intestinal toxicity was assessed by measuring intestinal permeability and by histological analyses of intestinal tissues. Metabolic changes were measured with H-1 nuclear magnetic resonance in serum and urine. Neither aflibercept nor erlotinib induced changes in intestinal permeability or intestinal tissue morphology. However, aflibercept treatment resulted in stunted body weight gain and altered choline, amino acid, and lipid metabolism. Two-week treatment with aflibercept or erlotinib alone does not induce observable changes in gastrointestinal morphology and function. However, observed aflibercept-treatment related metabolic changes suggest alterations in intestinal microbiota, nutrient intake, and adipose tissue function. The metabolic changes are also interesting in respect to the systemic effects of aflibercept and their possible associations with adverse events caused by aflibercept administration.

Place, publisher, year, edition, pages
Elsevier, 2019. Vol. 12, no 8, p. 1122-1130
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:oru:diva-83100DOI: 10.1016/j.tranon.2019.04.019ISI: 000474558700013PubMedID: 31176994Scopus ID: 2-s2.0-85066736520OAI: oai:DiVA.org:oru-83100DiVA, id: diva2:1439705
Note

Funding Agencies:

Cancer Society of Finland  

Finska Läkaresällskapet  

Foundation of Clinical Chemistry Research  

Biomedicum Helsinki Foundation  

Ministry of Economy and Competitiveness of Spain SAF2014-52875R

Instituto de Salud Carlos III

European Union (EU) PIE15/00013

Ministry of Science, Innovation and Universities  PCIN-2017-117

EU Joint Programming Initiative 'A Healthy Diet for a Healthy Life'  JPIHDHL INTIMIC-085

Spanish Government of Economy and Competitiveness (MINECO)  AGL2015-707487-P

Available from: 2020-06-12 Created: 2020-06-12 Last updated: 2020-06-12Bibliographically approved

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Forsgård, Richard A.

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