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 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.

Potential Ameliorative Effects of Qing Ye Dan Against Cadmium Induced Prostatic Deficits via Regulating Nrf-2/HO-1 and TGF-β1/Smad Pathways

“…Subsequently, Nrf-2 is dissociated, stabilized and translocated into the nucleus [20]. As a cell survival signaling, the activation of Nrf-2 will accelerate the production of endogenous antioxidant enzymes (including HO-1, CAT and SOD) via binding to the antioxidant response element in the promoter regions of these genes, and subsequently inducing their transcriptions [25]. Furthermore, HO-1 possessed both anti-inflammatory and anti-oxidative properties in response to oxidative stress [24].…”

“…TGF-β1 is a powerful pro-fibrogenic cytokine. It modulates the phenotype, proliferation and functions of fibroblasts, promotes the transdifferentiation of myofibroblasts, as well as induces the deposition of ECM [23, 25]. TGF-β superfamily elicit signaling through distinctly combining to their transmembrane receptors (TGF-βRI and II) [30].…”

Protective effect of gallic acid against bleomycin-induced pulmonary fibrosis in rats

“…TBARS levels most likely 292 determine the degree of organic lipid peroxidation, which denotes 293 the severity of cell membranes damage [41]. Chronic oral 294 administration of GA could increase the GPx activity which 295…”

“…response [41]. The protective effect of GA was also found for total 298 thiol which was applied for evaluation the non-enzymatic defense 299 potential of the cells against the oxidative stress [38].…”

Mesenchymal stem cells: A double‐edged sword in radiation‐induced lung injury

“…RPF, considered a result of chronic lung damage, occurs at 6–24 months post‐radiotherapy, and includes irreversible corruption of the alveoli, activation of myofibroblasts, abnormal deposition of extracellular collagen matrix, and deregulated remodeling of lung tissue . Clinical data have demonstrated that the incidence of RILI ranges from 20.3% to 36.9% . However, only a few successful therapeutic strategies have been proposed, despite extensive research.…”