title: The green tea extract epigallocatechin-3-gallate inhibits irradiation-induced pulmonary fibrosis in adult rats.
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 (60)Co 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
  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.
authors.affiliation: Affiliated Hospital of the Academy of Military Medical Sciences, Beijing 100071, P.R. China.
authors.forename: Hua
authors.initials: H
authors.lastname: You
authors.affiliation: 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.
authors.forename: Li
authors.initials: L
authors.lastname: Wei
authors.affiliation: Affiliated Hospital of the Academy of Military Medical Sciences, Beijing 100071, P.R. China.
authors.forename: Wan-Liang
authors.initials: WL
authors.lastname: Sun
authors.affiliation: Department of Cardiology, Cardiovascular Research Institute, Renmin Hospital, Wuhan University, Wuhan 430060, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, P.R. China.
authors.forename: Zai-Liang
authors.initials: ZL
authors.lastname: Yang
authors.affiliation: Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, P.R. China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Endocrine Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Ke
authors.initials: K
authors.lastname: Zheng
authors.affiliation: Clinical Laboratory, Beijing Chao-Yang Hospital, Capital Medical University, Beijing100020, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Affiliated Hospital of the Academy of Military Medical Sciences, Beijing 100071, P.R. China.
authors.forename: Wei-Jing
authors.initials: WJ
authors.lastname: Zhang
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000302:isolation & purification / Q000494:pharmacology*; D002392:Catechin / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D005720:Gamma Rays / Q000009:adverse effects; D015870:Gene Expression / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D006909:Hydroxyproline / Q000378:metabolism; D007274:Injections, Intraperitoneal; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D037701:Pulmonary Surfactant-Associated Protein B / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D013662:Tea / Q000737:chemistry*; D053773:Transforming Growth Factor beta1 / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D000199:Actins; D000975:Antioxidants; D015850:Interleukin-6; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D037701:Pulmonary Surfactant-Associated Protein B; D013662:Tea; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D003907:Dexamethasone; D002392:Catechin; C045651:epigallocatechin gallate; D051547:Heme Oxygenase-1; D016660:NAD(P)H Dehydrogenase (Quinone); C507703:NQO1 protein, rat; D006909:Hydroxyproline
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