title: The therapeutic effects of apigenin and dexamethasone on 5-fluorouracil-induced oral mucositis - a pilot study using a Syrian hamster model.
abstract: OBJECTIVE
  Oral mucositis (OM) is a common complication of chemotherapy and radiotherapy. The aim of this study was to evaluate the effects of treating 5-fluorouracil-induced OM with apigenin and dexamethasone.
  
  
  METHODS
  Thirty-six male Syrian hamsters were randomly assigned to one of three groups: control (50% acetic acid + 5-FU), 50% acetic acid + 5-FU + potassium Apigenin (KA), and 50% acetic acid + 5-FU + dexamethasone. The animals from each group were sacrificed 5, 7, 10, and 14 days after inducing the mucositis, and two samples collected from each animal, accounting a total of 72 samples. Macroscopic changes were assessed by histomorphometric analysis, with ulcers being assessed by imaging analysis and the number of inflammatory cells in the ulcerated region quantified in all periods through histomorphometric analysis (H&E). Furthermore, immunohistochemical changes were evaluated by proliferating cell nuclear antigen.
  
  
  RESULTS
  All groups presented an increased inflammatory infiltrate after 7 days, compared to other evaluation times (P ≥ 0.05). There was significant difference between apigenin and control group in the 10-days period. Lower quantity of inflammatory cells in the apigenin-treated group in comparison with control group in the 7- and 10-days periods was observed (P < 0.05). No statistically significant difference was verified among the groups in 5- and 14-days periods. The healing process of the control group was slower than that of apigenin and dexamethasone-treated groups, with an overall significant difference between apigenin and the control group in the 10-days period.
  
  
  CONCLUSIONS
  Apigenin treatment may enhance healing of OM induced by 5-fluorouracil, thus suggesting that more extensive research in this area may be useful to assess the role of agents of natural origin capable of preventing OM. Hence, further studies involving broader samples are need to confirm the therapeutic potential shown by this study.
authors.affiliation: Department of Oral Medicine, Ageing Research Institute, Faculty of Medicine and Dentistry, University of Murcia, Murcia, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Molina Prats
authors.affiliation: Pathologic Anatomy, Faculty of Medicine and Dentistry, University of Murcia, Murcia, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Gómez Garcia
authors.affiliation: Pathologic Anatomy, Faculty of Medicine and Dentistry, University of Murcia, Murcia, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Martinez Diaz
authors.affiliation: Department of Oral and Maxillofacial Medicine and Diagnostic Sciences, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Rui
authors.identifier: http://orcid.org/0000-0001-7628-8598
authors.initials: R
authors.lastname: Amaral Mendes
authors.affiliation: Department of Oral Medicine, Ageing Research Institute, Faculty of Medicine and Dentistry, University of Murcia, Murcia, Spain.
authors.forename: Pia
authors.initials: P
authors.lastname: Lopez-Jornet
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D047310:Apigenin / Q000627:therapeutic use*; D003907:Dexamethasone / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005472:Fluorouracil; D008297:Male; D008647:Mesocricetus; D010865:Pilot Projects; D013280:Stomatitis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000893:Anti-Inflammatory Agents; D003907:Dexamethasone; D047310:Apigenin; D005472:Fluorouracil
keywords: Syrian golden hamster; apigenin; dexamethasone; oral mucositis