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

Int J Mol Med. 2014 Jul;34(1):92-102. doi: 10.3892/ijmm.2014.1745. Epub 2014 Apr 16.

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / genetics
  • Actins / metabolism
  • Animals
  • Antioxidants / isolation & purification
  • Antioxidants / pharmacology*
  • Catechin / analogs & derivatives*
  • Catechin / isolation & purification
  • Catechin / pharmacology
  • Dexamethasone / pharmacology
  • Gamma Rays / adverse effects
  • Gene Expression / drug effects
  • Heme Oxygenase-1 / genetics
  • Heme Oxygenase-1 / metabolism
  • Hydroxyproline / metabolism
  • Injections, Intraperitoneal
  • Interleukin-10 / blood
  • Interleukin-6 / blood
  • Lung / drug effects*
  • Lung / metabolism
  • Lung / pathology
  • Male
  • NAD(P)H Dehydrogenase (Quinone) / genetics
  • NAD(P)H Dehydrogenase (Quinone) / metabolism
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism
  • Pulmonary Fibrosis / etiology
  • Pulmonary Fibrosis / metabolism
  • Pulmonary Fibrosis / pathology
  • Pulmonary Fibrosis / prevention & control*
  • Pulmonary Surfactant-Associated Protein B / genetics
  • Pulmonary Surfactant-Associated Protein B / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Severity of Illness Index
  • Tea / chemistry*
  • Transforming Growth Factor beta1 / blood
  • Tumor Necrosis Factor-alpha / blood

Substances

  • Actins
  • Antioxidants
  • Interleukin-6
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, rat
  • Pulmonary Surfactant-Associated Protein B
  • Tea
  • Transforming Growth Factor beta1
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Dexamethasone
  • Catechin
  • epigallocatechin gallate
  • Heme Oxygenase-1
  • NAD(P)H Dehydrogenase (Quinone)
  • NQO1 protein, rat
  • Hydroxyproline