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

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Forsgård , R A , Marrachelli , V G , Linden , J , Frias , R , Carmen Collado , M , Korpela , R , Monleon , D , Spillmann , T & Österlund , P 2019 , ' 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 ' , Translational oncology , vol. 12 , no. 8 , pp. 1122-1130 . https://doi.org/10.1016/j.tranon.2019.04.019

Title: 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
Author: Forsgård, Richard A.; Marrachelli, Vannina G.; Linden, Jere; Frias, Rafael; Carmen Collado, Maria; Korpela, Riitta; Monleon, Daniel; Spillmann, Thomas; Österlund, Pia
Contributor: University of Helsinki, Research Programs Unit
University of Helsinki, Veterinary Pathology and Parasitology
University of Helsinki, University Management
University of Helsinki, Thomas Spillmann / Principal Investigator
University of Helsinki, Department of Oncology
Date: 2019-08
Language: eng
Number of pages: 9
Belongs to series: Translational oncology
ISSN: 1936-5233
URI: http://hdl.handle.net/10138/304274
Abstract: 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.
Subject: METASTATIC COLORECTAL-CANCER
1ST-LINE TREATMENT
ANTITUMOR-ACTIVITY
OXIDATIVE STRESS
BEVACIZUMAB
COMBINATION
CELLS
CHEMOTHERAPY
TOXICITY
ACID
3122 Cancers
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