Amifostine reduces inflammation and protects against 5-fluorouracil-induced oral mucositis and hyposalivation

• Published in: Brazilian journal of medical and biological research Vol. 52; no. 3; p. e8251
• Main Authors: Barbosa, S C M, Pereira, V B M, Wong, D V T, Santana, A P M, Lucetti, L T, Carvalho, L L, Barbosa, C R N, Callado, R B, Silva, C A A, Lopes, C D H, Brito, G A C, Alencar, N M N, Lima-Júnior, R C P
• Format: Journal Article
• Language: English
• Published: Brazil Associacao Brasileira de Divulgacao Cientifica (ABDC) 01-01-2019; Revista Brasileira de Pesquisas Medicas; Associação Brasileira de Divulgação Científica
• Subjects: 5-Fluorouracil; Amifostine; Analysis; Anti-inflammatory agents; Antineoplastic agents; BIOLOGY; Cancer; Cancer chemotherapy toxicity; Cancer treatment; Carboplatin; Cheek pouch; Chemotherapy; Cytokines; Enzyme-linked immunosorbent assay; Fluorouracil; Hamsters; Health aspects; IL-1β; Immunohistochemistry; Inflammation; Interleukin 1; Interleukins; MEDICINE, RESEARCH & EXPERIMENTAL; Metastases; Mucositis; Necrosis; Neutrophils; Nitric oxide; Nitric-oxide synthase; Nitrogen oxides; Oral mucositis; Radiation therapy; Stomatitis; Toxicity; Trauma; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Tumors; Xerostomia; Brazil; Cancer chemotherapy toxicity; Oral mucositis; 5-Fluorouracil; Cytokines; Amifostine
• ISSN: 0100-879X; 1414-431X; 1414-431X; 1678-4510
• DOI: 10.1590/1414-431x20188251

Oral mucositis (OM) is a common and dose-limiting side effect of cancer treatment, including 5-fluorouracil (5-FU) and radiotherapy. The efficacy of the therapeutic measures to prevent OM is limited and disease prevention is not fully observable. Amifostine is a cytoprotective agent with a described anti-inflammatory potential. It is clinically used to reduce radiotherapy and chemotherapy-associated xerostomia. This study investigated the protective effect of amifostine on an experimental model of OM. Hamsters were divided into six groups: saline control group (5 mL/kg), mechanical trauma (scratches) of the right cheek pouch; 5-FU (60 and 40 mg/kg, ip, respectively, administered on days 1 and 2); amifostine (12.5, 25, or 50 mg/kg) + 5-FU + scratches. Salivation rate was assessed and the animals were euthanized on day 10 for the analysis of macroscopic and microscopic injury by scores. Tissue samples were harvested for the measurement of neutrophil infiltration and detection of inflammatory markers by ELISA and immunohistochemistry. 5-FU induced pronounced hyposalivation, which was prevented by amifostine (P<0.05). In addition, 5-FU injection caused pronounced tissue injury accompanied by increased neutrophil accumulation, tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β) tissue levels, and positive immunostaining for TNF-α, IL-1β, and inducible nitric oxide synthase (iNOS). Interestingly, amifostine prevented the inflammatory reaction and consequently improved macroscopic and microscopic damage (P<0.05 vs 5-FU group). Amifostine reduced inflammation and protected against 5-FU-associated oral mucositis and hyposalivation.