A PPAR-gamma agonist attenuates pulmonary injury induced by irradiation in a murine model

Lung Cancer : Journal of the International Association for the Study of Lung Cancer
Monica MangoniLorenzo Livi

Abstract

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. 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. 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. Rosiglitazone...Continue Reading

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Citations

Oct 27, 2016·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Sumit KumarRamovatar Meena
Apr 25, 2017·Radiation Research·Jian WangZhenyu Lin
Feb 17, 2018·Strahlentherapie und Onkologie : Organ der Deutschen Röntgengesellschaft ... [et al]·Danijela VasiljevicThomas Seppi
Jan 22, 2017·Asian Pacific Journal of Tropical Medicine·Ji-Hui YuJie-Ru You
Jun 18, 2017·Frontiers in Pharmacology·Benita L McVicker, Robert G Bennett
Dec 10, 2019·Current Cancer Drug Targets·Piotr Mrowka, Eliza Glodkowska-Mrowka
Nov 24, 2020·Future Medicinal Chemistry·Chengcheng XiaYan Gao

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