GSPE Protects against Bleomycin-Induced Pulmonary Fibrosis in Mice via Ameliorating Epithelial Apoptosis through Inhibition of Oxidative Stress

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease of unknown cause which leads to alveolar epithelial cell apoptosis followed by basement membrane disruption and accumulation of extracellular matrix, destroying the lung architecture. Oxidative stress is involved in the development of alveolar injury, inflammation, and fibrosis. Oxidative stress-mediated alveolar epithelial cell (AEC) apoptosis is suggested to be a key process in the pathogenesis of IPF. Therefore, the present study investigated whether grape seed proanthocyanidin extract (GSPE) could inhibit the development of pulmonary fibrosis via ameliorating epithelial apoptosis through the inhibition of oxidative stress. We found that GSPE significantly ameliorated the histological changes and the level of collagen deposition in bleomycin (BLM)-induced lungs. Moreover, GSPE attenuated lung inflammation by reducing the total number of cells in bronchoalveolar lavage (BAL) fluid and decreasing the expression of IL-6. We observed that the levels of H(2)O(2) leading to oxidative stress were increased following BLM instillation, which significantly decreased with GSPE treatment both in vivo and in vitro. These findings showed that GSPE attenuated BLM-induced epithelial apoptosis in the mouse lung and A549 alveolar epithelial cell through the inhibition of oxidative stress. Furthermore, GSPE could attenuate mitochondrial-associated cell apoptosis via decreasing the Bax/Bcl-2 ratio. The present study demonstrates that GSPE could ameliorate bleomycin-induced pulmonary fibrosis in mice via inhibition of epithelial apoptosis through the inhibition of oxidative stress.