Zingerone Attenuates bleomycin-Induced Pulmonary Fibrosis in Rats

Abstract

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive lung disorder that results in severe respiratory failure and death. The main characteristic of IPF is excess oxidative stress, fibroblast activation, increased collagen deposition, and multiple fibrotic lesions. Zingerone exhibits potent antioxidant, anti-inflammatory, and anti-fibrotic activities. Objectives: The aim of the study was to evaluate the protective effect of zingerone on bleomycin-induced pulmonary fibrosis (PF) and underlying mechanisms in rats. Methods: PF was induced by bleomycin (5 mg/kg, intratracheally) in male Sprague-Dawley rats and then, zingerone (10 - 40 mg/kg, orally) was administrated for 21 days’ post-bleomycin-instillation. After euthanizing the rats, the biochemical and histopathological markers of lung tissue were determined. Results: The findings showed that bleomycin significantly increased inflammatory and fibrotic responses, the level of malondialdehyde (MDA), the influx of inflammatory cells into the bronchoalveolar fluid (BALF), and hydroxyproline content of the lung (P < 0.01). In addition, the level of glutathione (GSH), the activity of superoxide dismutase (SOD) and glutathione peroxidase (GPx) decreased in the lung of bleomycin-instilled rats (P < 0.01). However, zingerone (20 and 40 mg/kg) significantly decreased histopathological injuries in H&E (Hematoxylin and eosin) and Masson’s trichrome-stained sections, hydroxyproline content and infiltration of leukocytes into BALF and oxidative markers, in a dose-dependent manner (P < 0.01). In addition, zingerone (40 mg/kg) significantly reduced the level of MDA in bleomycin-instilled rats (P < 0.01). Conclusions: These findings suggest that zingerone has protective effects against bleomycin-induced PF, which may be due to its anti-inflammatory and antioxidant activity.