title: A PPAR-gamma agonist attenuates pulmonary injury induced by irradiation in a murine model.
abstract: OBJECTIVE
  Due to its anti-inflammatory, antifibrotic and antineoplastic properties, the PPAR-γ agonist rosiglitazone is of interest in the prevention and therapy of radiation-induced pulmonary injury. We evaluated the radioprotective effects of rosiglitazone in a murine model of pulmonary damage to determine whether radioprotection was selective for normal and tumor tissues.
  
  
  METHODS
  Lungs in C57BL/6J mice were irradiated (19 Gy) with or without rosiglitazone (RGZ, 5mg/kg/day for 16 weeks, oral gavage). Computed tomography (CT) was performed and Hounsfield Units (HU) were determined during the observation period. Histological analysis and evaluation of fibrosis/inflammatory markers by western blot were performed at 16 weeks. A549 tumor-bearing CD1 mice were irradiated (16 Gy) with or without RGZ, and tumor volumes were measured at 35 days.
  
  
  RESULTS
  Rosiglitazone reduced radiologic and histologic signs of fibrosis, inflammatory infiltrate, alterations to alveolar structures, and HU lung density that was increased due to irradiation. RGZ treatment also significantly decreased Col1, NF-kB and TGF-β expression and increased Bcl-2 protein expression compared to the irradiation group and reduced A549 clonogenic survival and xenograft tumor growth.
  
  
  CONCLUSIONS
  Rosiglitazone exerted a protective effect on normal tissues in radiation-induced pulmonary injury, while irradiated lung cancer cells were not protected in vivo and in vitro. Thus, rosiglitazone could be proposed as a radioprotective agent in the treatment of lung cancer.
authors.affiliation: Radiotherapy Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Largo Brambilla 3, 50134 Florence, Italy. Electronic address: monica.mangoni@unifi.it.
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 Florence, Italy.
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 Florence, 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 Florence, Italy.
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Bonomo
authors.affiliation: Nuclear Medicine Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Largo Brambilla 3, 50134 Florence, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Bottoncetti
authors.affiliation: Department of Clinical and Experimental Medicine, University of Florence, Largo Brambilla 3, 50134 Florence, 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 Florence, Italy.
authors.forename: Ciro
authors.initials: C
authors.lastname: Franzese
authors.affiliation: Radiotherapy Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Largo Brambilla 3, 50134 Florence, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Cassani
authors.affiliation: Radiotherapy Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Largo Brambilla 3, 50134 Florence, 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 Florence, Italy.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Masoni
authors.affiliation: Radiotherapy Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Largo Brambilla 3, 50134 Florence, Italy.
authors.forename: Icro
authors.initials: I
authors.lastname: Meattini
authors.affiliation: Medical Physic Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Largo Brambilla 3, 50134 Florence, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Pallotta
authors.affiliation: Nuclear Medicine Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Largo Brambilla 3, 50134 Florence, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Passeri
authors.affiliation: Nuclear Medicine Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Largo Brambilla 3, 50134 Florence, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Pupi
authors.affiliation: Medical Physic Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Largo Brambilla 3, 50134 Florence, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Vanzi
authors.affiliation: Radiotherapy Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Largo Brambilla 3, 50134 Florence, 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 Florence, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Livi
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D004195:Disease Models, Animal; D006801:Humans; D055370:Lung Injury / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D047495:PPAR gamma / Q000819:agonists*; D011833:Radiation Injuries, Experimental; D011839:Radiation, Ionizing; D011837:Radiation-Protective Agents / Q000494:pharmacology; D011878:Radiotherapy / Q000009:adverse effects; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology; D014057:Tomography, X-Ray Computed; D023041:Xenograft Model Antitumor Assays
chemical_list: D047495:PPAR gamma; D011837:Radiation-Protective Agents; D045162:Thiazolidinediones; D000077154:Rosiglitazone
keywords: PPARgamma agonists; Radiation-induced lung toxicity; Radioprotection; Radiotherapy