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Preventive effects of curcumin and dexamethasone on lung transplantation-associated lung injury in rats

Sun, Jiayuan PhD; Guo, Weigang MD; Ben, Yong MM; Jiang, Jinjun MD; Tan, Changjun PhD; Xu, Zude PhD; Wang, Xiangdong MD, PhD; Bai, Chunxue MD, PhD

doi: 10.1097/CCM.0b013e31816a06fc
Laboratory Investigations
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Objective: To investigate potential effects of curcumin or dexamethasone on lung transplantation-associated lung injury.

Design: Prospective, randomized, controlled study.

Setting: Research laboratory.

Subjects: Adult male Sprague-Dawley rats.

Interventions: Sham-operated rats were used as time-matched controls. Experimental rats were subjected to unilateral orthotopic lung transplantation with 4 hrs of cold ischemia followed by 2 hrs (or 24 hrs) of reperfusion. Animals were randomly assigned to vehicle-, curcumin-, or dexamethasone-treated groups.

Measurements and Main Results: Transplantation-associated lung injury was characterized by an increased alveolar-capillary permeability and myeloperoxidase activity and decreased levels of arterial oxygen tension/inspired oxygen concentration ratio. Pretreatment with curcumin and dexamethasone significantly prevented barrier disruption, lung edema, tissue inflammation, and decreased Pao2 at the early stage of posttransplantation. Nuclear factor-κB in transplanted lungs was activated, accompanied by an increase in messenger RNA levels and protein content of tumor necrosis factor-α, interleukin-6, and matrix metalloproteinase-9 in lung graft. Those changes were prevented by pretreatment with curcumin and dexamethasone.

Conclusions: Curcumin can be an alternative therapy for protecting lung transplantation-associated injury by suppressing nuclear factor-κB-mediated expression of inflammatory genes.

From the Department of Pulmonary Medicine (JS, YB, JJ, XW, CB), Thoracic Surgery (WG), and Liver Surgery (CT), Zhongshan Hospital, Fudan University, Shanghai, PR China; and the Department of Pathology (ZX), Fudan University, Shanghai, PR China.

Supported, in part, by grant B115 from Shanghai Leading Academic Discipline Project, a grant for the study of diagnosis and treatment for acute respiratory distress syndrome from the China National Ministry of Health, and a grant for the study of diagnosis and treatment for respiratory failure and pulmonary infection from the Shanghai Municipal Health Bureau.

The authors have not disclosed any potential conflicts of interest.

Address requests for reprints to: Chunxue Bai, MD, PhD, Xiangdong Wang, MD, PhD, Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai 200032, PR China. E-mail: bai.chunxue@zs-hospital.sh.cn

© 2008 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins