Dietary Curcumin Increases Antioxidant Defenses in Lung, Ameliorates Radiation-Induced Pulmonary Fibrosis, and Improves Survival in Mice (original) (raw)

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12 February 2010 Dietary Curcumin Increases Antioxidant Defenses in Lung, Ameliorates Radiation-Induced Pulmonary Fibrosis, and Improves Survival in Mice

Author Affiliations +

James C. Lee,1 Paul A. Kinniry,1 Evguenia Arguiri,1 Matthew Serota,1 Stathis Kanterakis,1 Shampa Chatterjee,2 Charalambos C. Solomides,3 Prashanthi Javvadi,4 Constantinos Koumenis,4 Keith A. Cengel,4 Melpo Christofidou-Solomidou1

1aPulmonary, Allergy and Critical Care Division, Department of Medicine, University of Pennsylvania M
2dDepartment of Pharmacology, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania 1
3cDepartment of Pathology, Temple University Hospital, Philadelphia, Pennsylvania 19104
4bDepartment of Radiation Oncology, University of Pennsylvania Medical Center, Philadelphia, Pennsylv

Abstract

The effectiveness of lung radiotherapy is limited by radiation tolerance of normal tissues and by the intrinsic radiosensitivity of lung cancer cells. The chemopreventive agent curcumin has known antioxidant and tumor cell radiosensitizing properties. Its usefulness in preventing radiation-induced pneumonopathy has not been tested previously. We evaluated dietary curcumin in radiation-induced pneumonopathy and lung tumor regression in a murine model. Mice were given 1% or 5% (w/w) dietary curcumin or control diet prior to irradiation and for the duration of the experiment. Lungs were evaluated at 3 weeks after irradiation for acute lung injury and inflammation by evaluating bronchoalveolar lavage (BAL) fluid content for proteins, neutrophils and at 4 months for pulmonary fibrosis. In a separate series of experiments, an orthotopic model of lung cancer using intravenously injected Lewis lung carcinoma (LLC) cells was used to exclude possible tumor radioprotection by dietary curcumin. In vitro, curcumin boosted antioxidant defenses by increasing heme oxygenase 1 (HO-1) levels in primary lung endothelial and fibroblast cells and blocked radiation-induced generation of reactive oxygen species (ROS). Dietary curcumin significantly increased HO-1 in lungs as early as after 1 week of feeding, coinciding with a steady-state level of curcumin in plasma. Although both 1% and 5% w/w dietary curcumin exerted physiological changes in lung tissues by significantly decreasing LPS-induced TNF-α production in lungs, only 5% dietary curcumin significantly improved survival of mice after irradiation and decreased radiation-induced lung fibrosis. Importantly, dietary curcumin did not protect LLC pulmonary metastases from radiation killing. Thus dietary curcumin ameliorates radiation-induced pulmonary fibrosis and increases mouse survival while not impairing tumor cell killing by radiation.

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James C. Lee, Paul A. Kinniry, Evguenia Arguiri, Matthew Serota, Stathis Kanterakis, Shampa Chatterjee, Charalambos C. Solomides, Prashanthi Javvadi, Constantinos Koumenis, Keith A. Cengel, and Melpo Christofidou-Solomidou "Dietary Curcumin Increases Antioxidant Defenses in Lung, Ameliorates Radiation-Induced Pulmonary Fibrosis, and Improves Survival in Mice," Radiation Research 173(5), 590-601, (12 February 2010). https://doi.org/10.1667/RR1522.1

Received: 7 July 2008; Accepted: 1 November 2009; Published: 12 February 2010

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