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

Abstract

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.

Oral administration of nanomicelle curcumin in the prevention of radiotherapy‐induced mucositis in head and neck cancers

“…Oral mucositis (OM) is defined as erythematous and ulcerative lesions of the oral mucosa. It is among the clinically important and common side effects caused by chemotherapy and radiation therapy in cancer patients …”

“…Mucositis lesions are often extremely painful and may lead to oral discomfort, inadequate intake of food and medications, delays in cancer treatment, longer hospitalization time and consequently more costs and higher risk of life‐threatening infection . These complications may limit the patient's ability to tolerate an optimal antineoplastic treatment, which can negatively impact treatment planning and prognosis . It is therefore critical that mucositis can be prevented or treated to improve the overall care of patients with cancer.…”

“…can negatively impact treatment planning and prognosis. 2,6,7 It is therefore critical that mucositis can be prevented or treated to improve the overall care of patients with cancer.…”

Effect of Gold Nanoparticle on 5-Fluorouracil-Induced Experimental Oral Mucositis in Hamsters

“…Oral mucositis is induced with 5-fluorouracil (5-FU) followed by mechanical trauma (MT) [5,[22][23][24]. The induced mechanical trauma simulates irritating damages suffered by the oral mucosa of humans, which occur due to constant contact of the oral cavity with orthodontic appliances, maladaptive dental prostheses, and frequently used objects for hydration and feeding.…”

“…The induced mechanical trauma simulates irritating damages suffered by the oral mucosa of humans, which occur due to constant contact of the oral cavity with orthodontic appliances, maladaptive dental prostheses, and frequently used objects for hydration and feeding. These damages are promptly repaired in healthy individuals, in contrast to patients undergoing anticancer therapy [24].…”