Resveratrol Attenuates Hyperoxia-induced Oxidative Stress, Inflammation and Fibrosis and Suppresses Wnt/β-catenin Signaling in Lungs of Neonatal Rats.
Clin Exp Pharmacol Physiol. 2015 Jul 15. Epub 2015 Jul 15. PMID: 26174235
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-1β and interleukin-6 in the bronchoalveolar lavage fluid. Fibrotic-associated proteins transforming growth factor-β1, α-smooth muscle actin, collagen I and fibronectin deposition were also found in interstitial substance of lungs. Furthermore, Wnt/β-catenin signaling was found active in hyperoxia-induced lungs. In addition, expression of SP-C was increased and T1α was decreased in hyperoxia-exposed lungs. Resveratrol intraperitoneal administration alleviated hyperoxia-induced histological injury of lungs, regulated redox balance, decreased pro-inflammatory cytokines release, and down-regulated expression of fibrotic-associated proteins. Furthermore, Wnt/β-catenin signaling was also suppressed by resveratrol, as represented by diminished expression of lymphoid enhancer factor-1, Wnt induced signaling protein-1 and cyclin D1. In addition, the increase of SP-C and decrease of T1α expression was prevented as well. The present study showed that resveratrol could protect lungs from hyperoxia-induced injury through its antioxidant, anti-inflammatroy and anti-fibrotic effects. The transdifferentiation of alveolar epithelial type II cells to alveolar epithelial type Icells promotion and Wnt/β-catenin signaling suppression are also involved in the protective effect. This article is protected by copyright. All rights reserved.