Protective effect of dexamethasone on 5-FU-induced oral mucositis in hamsters

Oral mucositis (OM) is an important side effect of cancer treatment, characterized by ulcerative lesions in the mucosa of patients undergoing radiotherapy or chemotherapy, which has marked effects on patient quality of life and cancer therapy continuity. Considering that few protocols have demonstra...

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Published in:PloS one 2017-10, Vol.12 (10), p.e0186511-e0186511
Main Authors: Ribeiro, Susana Barbosa, de Araújo, Aurigena Antunes, Araújo Júnior, Raimundo Fernandes de, Brito, Gerly Anne de Castro, Leitão, Renata Carvalho, Barbosa, Maisie Mitchele, Garcia, Vinicius Barreto, Medeiros, Aldo Cunha, Medeiros, Caroline Addison Carvalho Xavier de
Format: Article
Language:English
Subjects:
5-Fluorouracil
AKT protein
Analysis
Animals
Biology and Life Sciences
Biophysics
Cancer
Cancer therapies
Cell division
Chemotherapy
Complications and side effects
Cricetinae
Cyclooxygenase 2 - metabolism
Cyclooxygenase-2
Cytokines
Cytokines - metabolism
Dexamethasone
Dexamethasone - pharmacology
Dosage and administration
Drug therapy
Fluorouracil
Fluorouracil - toxicity
Gene expression
Glucocorticoids
Hamsters
Health aspects
Immunoassays
Immunofluorescence
Interleukin 1
Kinases
Lesions
Leucine
Leucine zipper proteins
Leukocyte migration
Macrophage migration inhibitory factor
Macrophages
Male
MAP kinase
MAP kinase phosphatase
Matrix metalloproteinase
Matrix Metalloproteinase 2 - metabolism
Medicine and Health Sciences
Mesocricetus
Metalloproteinase
Morphology
Mucosa
Mucositis
NF-kappa B - metabolism
NF-κB protein
Phosphorylation
Polymerase chain reaction
Prevention
Protein kinase
Protein-serine/threonine kinase
Quality of life
Radiation therapy
Risk factors
Rodents
Side effects
Signal transduction
Signaling
Smad Proteins - metabolism
Steroids
Stomatitis - chemically induced
Stomatitis - metabolism
Stomatitis - prevention & control
Transcription factors
Transforming Growth Factor beta - metabolism
Trauma
Tumor necrosis factor-TNF
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Summary:Oral mucositis (OM) is an important side effect of cancer treatment, characterized by ulcerative lesions in the mucosa of patients undergoing radiotherapy or chemotherapy, which has marked effects on patient quality of life and cancer therapy continuity. Considering that few protocols have demonstrated efficacy in preventing this side effect, the aim of this study was to examine the effect of dexamethasone (DEX) on OM induced by 5-fluorouracil (5-FU) in hamsters by studying signaling pathways. OM was induced in hamsters by 5-FU followed by mechanical trauma (MT) on day 4. On day 10, the animals were euthanized. The experimental groups included saline, MT, 5-FU, and DEX (0.25, 0.5, or 1 mg/kg). Macroscopic, histopathological, and immunohistochemical analyses as well as immunofluorescence experiments were performed on the oral mucosa of the animals. The oral mucosal samples were analyzed by enzyme-linked immunosorbent assays, and quantitative real-time polymerase chain reaction (qPCR). DEX (0.5 or 1 mg/kg) reduced inflammation and ulceration of the oral mucosa of hamsters. In addition, DEX (1 mg/kg) reduced the cytokine levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and macrophage migration inhibitory factor (MIF). DEX (1 mg/kg) also reduced the immunoexpression of cyclooxygenase (COX)-2, matrix metalloproteinase (MMP)-2, transforming growth factor (TGF)-β, MIF, Smad 2/3, Smad 2/3 phosphorylated and NFκB p65 in the jugal mucosa. Finally, DEX (1 mg/kg) increased interleukin-1 receptor-associated kinase 3 (IRAK-M), glucocorticoid-induced leucine zipper (GILZ), and mitogen-activated protein kinase (MKP1) gene expression and reduced NFκB p65 and serine threonine kinase (AKt) gene expression, relative to the 5-FU group. Thus, DEX improved OM induced by 5-FU in hamsters.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0186511