An evaluation of the effects of glabridin and dexamethasone in bleomycin-induced pulmonary fibrosis: The role of BKCa channels

Pulmonary fibrosis is a refractory entity with a progressive course and no effective therapeutic options. The purpose of this study was to investigate the potential involvement of both glabridin and dexamethasone (Dex) in inflammatory and fibrotic responses in a bleomycin (BLM)-induced pulmonary fibrosis model. The role of Ca+2-activated K+ channels (BKCa) in the anti-inflammatory effects of glabridin was also examined. Adult female Wistar rats were divided into six groups: saline control, BLM, BLM+Gla (BLM+glabridin), BLM+IbTX+Gla (BLM+iberiotoxin+Gla, BKCa channel blocker), BLM+Dex, and BLM+Veh (BLM+dimethylsulfoxide). Inflammatory cell count values, and interleukin (IL)− 6, tumor necrosis factor (TNF)-α, glutathione (GSH), and malondialdehyde (MDA) levels were measured in bronchoalveolar lavage (BAL) fluid in order to measure fibrosis and the extent of tissue damage, in addition to stereological, immunohistochemical and histopathological examinations. Whole-body plethysmography was used to evaluate pulmonary function. Treatments with glabridin and Dex significantly reduced pathological injury and fibrosis in lung tissue, levels of TNF-α and IL-6 increased by BLM, oxidative stress, and fibrillin-1 scoring. Glabridin and Dex also reversed the increases observed in neutrophil, lymphocyte, and macrophage counts in BAL fluid induced by BLM. Glabridin and Dex were found to ameliorate the abnormal course of PIF, PEF, EV, TV, f, and Penh values caused by BLM. Our findings suggest that glabridin and Dex may exert anti-fibrotic effects by suppressing oxidative stress and inhibiting the inflammatory response, and that glabridin may improve pulmonary function through activation of BKCa channels. Both glabridin and Dex may therefore be of therapeutic use in pulmonary fibrosis.