Evaluation of potential anti-fibrotic effect of oleuropein on bleomycin-induced pulmonary fibrosis in rat

Abstract

The etiology of idiopathic pulmonary fibrosis (IPF) is not well known, however it is a final response of frequent injuries to endothelial and epithelial cells that cause influx of the inflammatory cells. Bleomycin (BLM), a chemotherapeutic agent that causes lung fibrosis in human patients has been applied extensively in rodent models to inducing IPF. Moreover, oxidative stress and production of reactive oxygen species (ROS) have been involved in the pathogenesis. We aimed to investigate the effect of main olive antioxidant and anti-inflammatory polyphenol constituent, oleuropein (OLE), on BLM-induced fibrosis model. Female Wistar rats were divided into six groups (n = 8). In this study, whereas negative group only received vehicle and treatment groups received OLE (20, 40, and 80 mg kg⁻¹) orally. Also, positive control group received intratracheally (IT), single dose BLM (7.5 U kg⁻¹), prednisolone (10 mg/kg) as standard cure a week before and 3 weeks after IT-BLM. At 21th day of experiment, IL-13, TNF, TGF-β, and PDGF in the bronchoalveolar fluid (BALF), lung content hydroxyproline (HP), and malondialdehyde (MDA) were quantified. Histopathological changes in lungs were investigated too. IL-13, TNF, TGF-β₁, PDGF in BALF, lung HP (collagen index), and MDA content in BLM-injected group was significantly higher than the control group (p < .05). In contrast, rats treated with OLE showed obviously lesser contents. Also, the histopathological observation confirms these findings. The results indicate that treatment by OLE may inhibit production of anti-inflammatory cytokines and ROS, and thus could be a useful medicine for managing fingagin disorders.

Keywords:

• Bleomycin
• oleuropein
• pulmonary fibrosis
• reactive oxygen species
• rat

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The authors would like to thank student Research Committee, Ahvaz Jundishapur University of Medical Sciences for providing financial supported by the grant [IR.AJUMS.REC.1396.292 and IR.AJUMS.REC.1396.32] of this research.