Attenuation of Bleomycin-Induced Pulmonary Fibrosis in Wistar Rats by Combination Treatment of Two Natural Phenolic Compounds: Quercetin and Gallic Acid.

The present study aimed to investigate the protective effects of two potent natural antioxidants, gallic acid and quercetin as single or combination treatment against bleomycin-induced pulmonary fibrosis (PF). A total of 50 Wistar rats were randomly divided into 5 groups. Group 1 and 2 intratracheally received saline and bleomycin (7.5 UI/kg), respectively, on day 7, accompanied by oral saline administration for 28 day. Groups 3, 4, and 5 received a single dose of bleomycin on day 7, accompanied by oral administration of gallic acid, quercetin, and their combination, respectively, for 28 day. Finally, the lungs were removed for biochemical and histopathological tests. The combination treatment demonstrated a remarkable decrease in lung hydroxyproline and TNF-α level and increase in catalase activity as compared with both single phytochemical-treated groups. The combination treatment significantly enhanced lung SOD activity and GSH level and decreased NO and IL-6 levels as compared with quercetin-treated group. However, only combination treatment could decrease the lung index and completely reversed histopathological changes in the bleomycin-treated group. In sum, when compared to a single exposure, the combination treatment might be a more effective approach for PF treatment because of its superior efficacy in reversing lung histological changes in the bleomycin-treated group.