The green tea extract epigallocatechin-3-gallate inhibits irradiation-induced pulmonary fibrosis in adult rats

You,Hua; Wei,Li; Sun,Wan-Liang; Wang,Lei; Yang,Zai-Liang; Liu,Yuan; Zheng,Ke; Wang,Ying; Zhang,Wei-Jing

doi:10.3892/ijmm.2014.1745

The green tea extract epigallocatechin-3-gallate inhibits irradiation-induced pulmonary fibrosis in adult rats

Authors:
- Hua You
- Li Wei
- Wan-Liang Sun
- Lei Wang
- Zai-Liang Yang
- Yuan Liu
- Ke Zheng
- Ying Wang
- Wei-Jing Zhang
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Affiliations: Affiliated Hospital of the Academy of Military Medical Sciences, Beijing 100071, P.R. China, Key Laboratory of Birth Defects and Reproductive Health of the National Health and Family Commission, Chongqing Population and the Family Planning Science and Technology Research Institute, Chongqing 400020, P.R. China, Department of Cardiology, Cardiovascular Research Institute, Renmin Hospital, Wuhan University, Wuhan 430060, P.R. China, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, P.R. China, Department of Endocrine Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China, Clinical Laboratory, Beijing Chao-Yang Hospital, Capital Medical University, Beijing100020, P.R. China
Published online on: April 16, 2014 https://doi.org/10.3892/ijmm.2014.1745
Pages: 92-102
Copyright: © You et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

The present study evaluated the effect of epigallocatechin-3-gallate (EGCG), the most abundant catechin in green tea, on irradiation-induced pulmonary fibrosis and elucidated its mechanism of action. A rat model of irradiation-induced pulmonary fibrosis was generated using a 60Co irradiator and a dose of 22 Gy. Rats were intraperitoneally injected with EGCG (25 mg/kg) or dexamethasone (DEX; 5 mg/kg) daily for 30 days. Mortality rates and lung index values were calculated. The severity of fibrosis was evaluated by assaying the hydroxyproline (Hyp) contents of pulmonary and lung tissue sections post-irradiation. Alveolitis and fibrosis scores were obtained from semi-quantitative analyses of hematoxylin and eosin (H&E) and Masson's trichrome lung section staining, respectively. The serum levels of transforming growth factor β1 (TGF-β1), interleukin (IL)-6, IL-10, and tumor necrosis factor-α (TNF-α) were also measured. Surfactant protein-B (SPB) and α-SMA expression patterns were evaluated using immunohistochemistry, and the protein levels of nuclear transcription factor NF-E2-related factor 2 (Nrf-2) and its associated antioxidant enzymes heme oxygenase-1 enzyme (HO-1) and NAD(P)H:quinone oxidoreductase-1 (NQO-1) were examined via western blot analysis. Treatment with EGCG, but not DEX, reduced mortality rates and lung index scores, improved histological changes in the lung, reduced collagen depositions, reduced MDA content, enhanced SOD activity, inhibited (myo)fibroblast proliferation, protected alveolar epithelial type II (AE2) cells, and regulated serum levels of TGF-β1, IL-6, IL-10, and TNF-α. Treatment with EGCG, but not DEX, activated Nrf-2 and its downstream antioxidant enzymes HO-1 and NQO-1. Taken together, these results showed that EGCG treatment significantly inhibits irradiation-induced pulmonary fibrosis. Furthermore, the results suggested promising clinical EGCG therapies to treat this disorder.

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1	Almeida C, Nagarajan D, Tian J, et al: The role of alveolar epithelium in radiation-induced lung injury. PLoS One. 8:e536282013. View Article : Google Scholar : PubMed/NCBI
2	Epperly MW, Guo H, Gretton JE and Greenberger JS: Bone marrow origin of myofibroblasts in irradiation pulmonary fibrosis. Am J Respir Cell Mol Biol. 29:213–224. 2003. View Article : Google Scholar : PubMed/NCBI
3	Matsuo Y, Shibuya K, Nakamura M, et al: Dose-volume metrics associated with radiation pneumonitis after stereotactic body radiation therapy for lung cancer. Int J Radiat Oncol Biol Phys. 83:e545–e549. 2012.PubMed/NCBI
4	Minor GI, Yashar CM, Spanos WJ Jr, et al: The relationship of radiation pneumonitis to treated lung volume in breast conservation therapy. Breast J. 12:48–52. 2006.PubMed/NCBI
5	Rosenzweig KE, Zauderer MG, Laser B, et al: Pleural intensity-modulated radiotherapy for malignant pleural mesothelioma. Int J Radiat Oncol Biol Phys. 83:1278–1283. 2012. View Article : Google Scholar : PubMed/NCBI
6	Liu HW, Seftel MD, Rubinger M, et al: Total body irradiation compared with BEAM: long-term outcomes of peripheral blood autologous stem cell transplantation for non-Hodgkin’s lymphoma. Int J Radiat Oncol Biol Phys. 78:513–520. 2010.PubMed/NCBI
7	Zhang Y, Zhang X, Rabbani ZN, Jackson IL and Vujaskovic Z: Oxidative stress mediates radiation lung injury by inducing apoptosis. Int J Radiat Oncol Biol Phys. 83:740–748. 2012. View Article : Google Scholar : PubMed/NCBI
8	Mak JC: Potential role of green tea catechins in various disease therapies: progress and promise. Clin Exp Pharmacol Physiol. 39:265–273. 2012. View Article : Google Scholar : PubMed/NCBI
9	Li CP, Yao J, Tao ZF, Li XM, Jiang Q and Yan B: Epigallocatechin-gallate (EGCG) regulates autophagy in human retinal pigment epithelial cells: a potential role for reducing UVB light-induced retinal damage. Biochem Biophys Res Commun. 438:739–745. 2013. View Article : Google Scholar : PubMed/NCBI
10	Donà M, Dell’Aica I, Calabrese F, et al: Neutrophil restraint by green tea: inhibition of inflammation, associated angiogenesis, and pulmonary fibrosis. J Immunol. 170:4335–4341. 2003.PubMed/NCBI
11	Sriram N, Kalayarasan S and Sudhandiran G: Epigallocatechin-3-gallate exhibits anti-fibrotic effect by attenuating bleomycin-induced glycoconjugates, lysosomal hydrolases and ultrastructural changes in rat model pulmonary fibrosis. Chem Biol Interact. 180:271–280. 2009. View Article : Google Scholar
12	Sriram N, Kalayarasan S and Sudhandiran G: Epigallocatechin-3-gallate augments antioxidant activities and inhibits inflammation during bleomycin-induced experimental pulmonary fibrosis through Nrf2-Keap1 signaling. Pulm Pharmacol Ther. 22:221–236. 2009. View Article : Google Scholar
13	Sriram N, Kalayarasan S and Sudhandiran G: Enhancement of antioxidant defense system by epigallocatechin-3-gallate during bleomycin induced experimental pulmonary fibrosis. Biol Pharm Bull. 31:1306–1311. 2008. View Article : Google Scholar : PubMed/NCBI
14	Tipoe GL, Leung TM, Liong EC, Lau TY, Fung ML and Nanji AA: Epigallocatechin-3-gallate (EGCG) reduces liver inflammation, oxidative stress and fibrosis in carbon tetrachloride (CCl4)-induced liver injury in mice. Toxicology. 273:45–52. 2010. View Article : Google Scholar : PubMed/NCBI
15	de Vries HE, Witte M, Hondius D, et al: Nrf2-induced antioxidant protection: a promising target to counteract ROS-mediated damage in neurodegenerative disease? Free Radic Biol Med. 45:1375–1383. 2008.PubMed/NCBI
16	Zhang L, Dong XW, Wang JN, et al: PEP-1-CAT-transduced mesenchymal stem cells acquire an enhanced viability and promote ischemia-induced angiogenesis. PLoS One. 7:e525372012. View Article : Google Scholar : PubMed/NCBI
17	Zhang YE, Fu SZ, Li XQ, et al: PEP-1-SOD1 protects brain from ischemic insult following asphyxial cardiac arrest in rats. Resuscitation. 82:1081–1086. 2011. View Article : Google Scholar
18	Szapiel SV, Elson NA, Fulmer JD, Hunninghake GW and Crystal RG: Bleomycin-induced interstitial pulmonary disease in the nude, athymic mouse. Am Rev Respir Dis. 120:893–899. 1979.PubMed/NCBI
19	Williams JP, Johnston CJ and Finkelstein JN: Treatment for radiation-induced pulmonary late effects: spoiled for choice or looking in the wrong direction? Curr Drug Targets. 11:1386–1394. 2010. View Article : Google Scholar : PubMed/NCBI
20	Rizvi M, Pathak D, Freedman JE and Chakrabarti S: CD40-CD40 ligand interactions in oxidative stress, inflammation and vascular disease. Trends Mol Med. 14:530–538. 2008. View Article : Google Scholar : PubMed/NCBI
21	Mikkelsen RB and Wardman P: Biological chemistry of reactive oxygen and nitrogen and radiation-induced signal transduction mechanisms. Oncogene. 22:5734–5754. 2003. View Article : Google Scholar : PubMed/NCBI
22	Hügel HM and Jackson N: Redox chemistry of green tea polyphenols: therapeutic benefits in neurodegenerative diseases. Mini Rev Med Chem. 12:380–387. 2012.PubMed/NCBI
23	Del Rio D, Stewart AJ and Pellegrini N: A review of recent studies on malondialdehyde as toxic molecule and biological marker of oxidative stress. Nutr Metab Cardiovasc Dis. 15:316–328. 2005.PubMed/NCBI
24	Lefaix JL, Delanian S, Leplat JJ, et al: Successful treatment of radiation-induced fibrosis using Cu/Zn-SOD and Mn-SOD: an experimental study. Int J Radiat Oncol Biol Phys. 35:305–312. 1996. View Article : Google Scholar : PubMed/NCBI
25	Vujaskovic Z, Batinic-Haberle I, Rabbani ZN, et al: A small molecular weight catalytic metalloporphyrin antioxidant with superoxide dismutase (SOD) mimetic properties protects lungs from radiation-induced injury. Free Radic Biol Med. 33:857–863. 2002. View Article : Google Scholar
26	Schaue D, Kachikwu EL and McBride WH: Cytokines in radiobiological responses: a review. Radiat Res. 178:505–523. 2012. View Article : Google Scholar : PubMed/NCBI
27	Martin M, Lefaix J and Delanian S: TGF-beta1 and radiation fibrosis: a master switch and a specific therapeutic target? Int J Radiat Oncol Biol Phys. 47:277–290. 2000. View Article : Google Scholar : PubMed/NCBI
28	Wang J, Qiao XY, Lu FH, et al: TGF-beta1 in serum and induced sputum for predicting radiation pneumonitis in patients with non-small cell lung cancer after radiotherapy. Chin J Cancer. 29:325–329. 2010. View Article : Google Scholar : PubMed/NCBI
29	Dong XR, Wang JN, Liu L, et al: Modulation of radiation-induced tumour necrosis factor-α and transforming growth factor β1 expression in the lung tissue by Shengqi Fuzheng injection. Mol Med Rep. 3:621–627. 2010.
30	Wynn TA: Integrating mechanisms of pulmonary fibrosis. J Exp Med. 208:1339–1350. 2011. View Article : Google Scholar : PubMed/NCBI
31	Denis M: Interleukin-6 in mouse hypersensitivity pneumonitis: changes in lung free cells following depletion of endogenous IL-6 or direct administration of IL-6. J Leukoc Biol. 52:197–201. 1992.
32	Zdanov A: Structural features of the interleukin-10 family of cytokines. Curr Pharm Des. 10:3873–3884. 2004. View Article : Google Scholar : PubMed/NCBI
33	Alhamad EH, Cal JG, Shakoor Z, Almogren A and Alboukai AA: Cytokine gene polymorphisms and serum cytokine levels in patients with idiopathic pulmonary fibrosis. BMC Med Genet. 14:662013. View Article : Google Scholar : PubMed/NCBI
34	Barbarin V, Xing Z, Delos M, Lison D and Huaux F: Pulmonary overexpression of IL-10 augments lung fibrosis and Th2 responses induced by silica particles. Am J Physiol Lung Cell Mol Physiol. 288:L841–L848. 2005. View Article : Google Scholar : PubMed/NCBI
35	Bae HB, Li M, Kim JP, et al: The effect of epigallocatechin gallate on lipopolysaccharide-induced acute lung injury in a murine model. Inflammation. 33:82–91. 2010. View Article : Google Scholar : PubMed/NCBI
36	Sun Q, Zheng Y, Zhang X, et al: Novel immunoregulatory properties of EGCG on reducing inflammation in EAE. Front Biosci (Landmark Ed). 18:332–342. 2013. View Article : Google Scholar : PubMed/NCBI
37	Sahin K, Tuzcu M, Gencoglu H, et al: Epigallocatechin-3-gallate activates Nrf2/HO-1 signaling pathway in cisplatin-induced nephrotoxicity in rats. Life Sci. 87:240–245. 2010. View Article : Google Scholar : PubMed/NCBI