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Resveratrol attenuates hyperoxia‐induced oxidative stress, inflammation and fibrosis and suppresses Wnt/ β ‐catenin signalling in lungs of neonatal rats
Author(s) -
Xu Wei,
Zhao Ying,
Zhang Binglun,
Xu Bo,
Yang Yang,
Wang Yujing,
Liu Chunfeng
Publication year - 2015
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12459
Subject(s) - hyperoxia , resveratrol , oxidative stress , bronchopulmonary dysplasia , pulmonary fibrosis , endocrinology , fibrosis , wnt signaling pathway , lung , medicine , chemistry , cancer research , immunology , pathology , biology , pharmacology , signal transduction , biochemistry , pregnancy , gestational age , genetics
Summary Although survival rate of infants born prematurely has been raised by supplemental oxygen treatment, it is followed by high morbidity of hyperoxia‐induced bronchopulmonary dysplasia. In this study, the effect of resveratrol on the lung injury was evaluated in hyperoxia‐exposed rats of preterm birth. The results demonstrated that hyperoxia led to thickened alveolar wall, simplified alveolar architecture and fibrosis. In addition, elevated methane dicarboxylic aldehyde level, decreased glutathione level and superoxide dismutase activity were also found in hyperoxic lungs, as well as the increased tumor necrosis factor‐ α , interleukin‐1 β and interleukin‐6 in the bronchoalveolar lavage fluid. Fibrotic‐associated proteins transforming growth factor‐ β 1, α ‐smooth muscle actin, collagen I and fibronectin deposition were also found in interstitial substance of lungs. Furthermore, Wnt/ β ‐catenin signalling was found to be active in hyperoxia‐induced lungs. In addition, expression of SP ‐C was increased and T1 α was decreased in hyperoxia‐exposed lungs. Resveratrol intraperitoneal administration alleviated hyperoxia‐induced histological injury of lungs, regulated redox balance, decreased pro‐inflammatory cytokine release, and down‐regulated expression of fibrotic‐associated proteins. Furthermore, Wnt/ β ‐catenin signalling was also suppressed by resveratrol, as represented by diminished expression of lymphoid enhancer factor‐1, Wnt induced signalling protein‐1 and cyclin D1. In addition, the increase of SP ‐C and decrease of T1 α expression was prevented as well. The present study showed that resveratrol could protect lungs from hyperoxia‐induced injury through its antioxidant, anti‐inflammatory and anti‐fibrotic effects. The transdifferentiation of alveolar epithelial type II cells to alveolar epithelial type I cells promotion and Wnt/ β ‐catenin signalling suppression are also involved in the protective effect.