title: A PPAR gamma agonist protects against oral mucositis induced by irradiation in a murine model.
abstract: Due to its anti-inflammatory, antifibrotic and antineoplastic properties, the PPAR gamma agonist rosiglitazone is of interest in prevention and therapy of radiation-induced toxicities. We aimed to evaluate the radioprotective effect of rosiglitazone in a mouse model of radiation-induced oral mucositis.
  
  
  
  Oral mucositis was obtained by irradiation of the oral region of C57BL/6J mice, pretreated or not with rosiglitazone. Mucositis was assessed by macroscopic scoring, histology and molecular analysis. Tumor xenograft was obtained by s.c. injection of Hep-2 cells in CD1 mice. Tumor volume was measured twice a week to evaluate effect of rosiglitazone alone and combined with radiotherapy.
  
  
  
  Irradiated mice showed typical features of oral mucositis, such as oedema and reddening, reaching the peak of damage after 12-15days. Rosiglitazone markedly reduced visible signs of mucositis and significantly reduced the peak. Histological analysis showed the presence of an inflammatory cell infiltrate after irradiation; the association with rosiglitazone noticeably reduced infiltration. Rosiglitazone significantly inhibited radiation-induced tnfα, Il-6 and Il-1β gene expression. Rosiglitazone controlled the increase of TGF-β and NF-kB p65 subunit proteins induced by irradiation, and enhanced the expression of catalase. Irradiation and rosiglitazone significantly reduced tumor volume as compared to control. Rosiglitazone did not protect tumor from the therapeutic effect of radiation.
  
  
  
  Rosiglitazone exerted a protective action on normal tissues in radiation-induced mucositis. Moreover, it showed antineoplastic properties on head-neck carcinoma xenograft model and selective protection of normal tissues. Thus, PPAR gamma agonists should be further investigated as radioprotective agents in head and neck cancer.
authors.affiliation: Radiotherapy Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Largo Brambilla 3, 50134 Firenze, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Mangoni
authors.affiliation: Radiotherapy Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Largo Brambilla 3, 50134 Firenze, Italy. Electronic address: mariangela.sottili@unifi.it.
authors.forename: Mariangela
authors.initials: M
authors.lastname: Sottili
authors.affiliation: Radiotherapy Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Largo Brambilla 3, 50134 Firenze, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Gerini
authors.affiliation: Radiotherapy Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Largo Brambilla 3, 50134 Firenze, Italy.
authors.forename: Isacco
authors.initials: I
authors.lastname: Desideri
authors.affiliation: Medical Physic Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Largo Brambilla 3, 50134 Firenze, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Bastida
authors.affiliation: Medical Physic Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Largo Brambilla 3, 50134 Firenze, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Pallotta
authors.affiliation: Department of Clinical and Experimental Medicine, University of Florence, Largo Brambilla 3, 50134 Firenze, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Castiglione
authors.affiliation: Radiotherapy Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Largo Brambilla 3, 50134 Firenze, Italy.
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Bonomo
authors.affiliation: Radiotherapy Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Largo Brambilla 3, 50134 Firenze, Italy.
authors.forename: Icro
authors.initials: I
authors.lastname: Meattini
authors.affiliation: Radiotherapy Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Largo Brambilla 3, 50134 Firenze, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Greto
authors.affiliation: Radiotherapy Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Largo Brambilla 3, 50134 Firenze, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Olmetto
authors.affiliation: Radiotherapy Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Largo Brambilla 3, 50134 Firenze, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Terziani
authors.affiliation: Radiotherapy Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Largo Brambilla 3, 50134 Firenze, Italy.
authors.forename: Carlotta
authors.initials: C
authors.lastname: Becherini
authors.affiliation: Radiotherapy Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Largo Brambilla 3, 50134 Firenze, Italy.
authors.forename: Camilla
authors.initials: C
authors.lastname: Delli Paoli
authors.affiliation: Radiotherapy Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Largo Brambilla 3, 50134 Firenze, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Trombetta
authors.affiliation: Radiotherapy Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Largo Brambilla 3, 50134 Firenze, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Loi
authors.affiliation: Radiotherapy Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Largo Brambilla 3, 50134 Firenze, Italy.
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Biti
authors.affiliation: Radiotherapy Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Largo Brambilla 3, 50134 Firenze, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Livi
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D051379:Mice; D008810:Mice, Inbred C57BL; D047495:PPAR gamma / Q000819:agonists*; D011878:Radiotherapy / Q000009:adverse effects*; D013280:Stomatitis / Q000209:etiology / Q000517:prevention & control*
chemical_list: D047495:PPAR gamma
keywords: Oral mucositis; PPAR gamma agonists; Radiation-induced toxicity; Radioprotection; Rosiglitazone