Antiinflammation and Antioxidant Effects of Thalidomide on Pulmonary Fibrosis in Mice and Human Lung Fibroblasts
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ORIGINAL ARTICLE
Antiinflammation and Antioxidant Effects of Thalidomide on Pulmonary Fibrosis in Mice and Human Lung Fibroblasts Xiaoying Dong,1 Xin Li,1 Minghui Li,1 Ming Chen,1 Qian Fan,1 and Wei Wei
1,2
Abstract—In this study, the potential effects of thalidomide (Thal) on bleomycin (BLM)-induced pulmonary fibrosis were investigated. BALB/C mice model of pulmonary fibrosis induced by an intratracheal instillation of BLM was adopted, and then was intraperitoneally injected with Thal (10, 20, 50 mg/kg) daily for 8 days, while the control and BLM-treated mouse groups were injected with a saline solution. The effects of Thal on pulmonary injury were evaluated by the lung wet/dry weight ratios and histopathological examination. Inflammation of lung tissues was assessed by measuring the levels of interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-β in bronchoalveolar lavage fluid. Oxidative stress was evaluated by detecting the levels of reactive oxygen species (ROS), superoxide dismutase (SOD), total antioxidant capacity (T-AOC), and malondialdehyde (MDA) in lung tissue. The results indicated that Thal treatment remarkably attenuated pulmonary fibrosis, oxidative stress, and inflammation in mouse lungs. The antiinflammatory and antioxidant effects of Thal were also found in human lung fibroblasts. Thal administration significantly enhanced the activity of thioredoxin reductase; however, the other enzymes or proteins involved in biologic oxidation-reduction equilibrium were not affected. Our findings indicate that Thal-mediated suppression of pulmonary fibrosis is related to the inhibition of oxidative stress and inflammatory response. In summary, these results may provide a rationale to explore clinical application of Thal for the prevention of pulmonary fibrosis. KEY WORDS: thalidoamide; pulmonary fibrosis; oxidative stress; inflammation; thioredoxin reductase.
INTRODUCTION Diffuse interstitial lung disease is characterized by varying degrees of inflammation and fibrosis resulting in derangement of the gas-exchange units of the lung. Around half of interstitial lung diseases are of unknown etiology and are classified as idiopathic interstitial pneumonias [1]. By far, the most common one is idiopathic pulmonary fibrosis, the prognosis of which is worse than that of many cancers [2, 3]. Pulmonary fibrosis has an aggressive course and is usually fatal at an average of 3 to 6 years after the onset of 1
Department of Rheumatism and Immunity, General Hospital of Tianjin Medical University, Tianjin, 300052, China 2 To whom correspondence should be addressed at Department of Rheumatism and Immunity, General Hospital of Tianjin Medical University, Tianjin, 300052, China. E-mail: [email protected]
symptoms [3–6]. Pulmonary fibrosis refers to a series of lung diseases characterized by inflammation, fibroblast proliferation, and excessive collagen deposition. Although the mechanisms underlying pulmonary fibrosis are not clearly understood, current evidence suggests that it is a
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