Therapeutic use of fisetin and pirfenidone combination in bleomycin-induced pulmonary fibrosis in adult male albino rats

Area of Science:

• Pulmonary Medicine
• Pharmacology
• Biochemistry

Background:

• Pulmonary fibrosis (PF) is a significant health concern.
• Pirfenidone (PFD) is a key drug for treating PF.
• Fisetin (FST), a flavonoid, exhibits antioxidant, anti-inflammatory, and antifibrotic properties.

Purpose of the Study:

• To investigate the combined therapeutic effects of PFD and FST on bleomycin (BLM)-induced pulmonary fibrosis in rats.
• To evaluate the impact of combined PFD and FST on fibrotic markers, oxidative stress, and inflammatory responses.

Main Methods:

• Pulmonary fibrosis was induced in male Wistar rats using bleomycin (BLM).
• Rats were divided into five groups: Sham, BLM, BLM + PFD, BLM + FST, and BLM + PFD + FST.
• Treatment involved daily administration of PFD (50 mg/kg) and/or FST (25 mg/kg) for 15 days, followed by histopathological, biochemical, and RT-PCR analyses of lung tissue and BAL fluid.

Main Results:

• Combined PFD and FST treatment downregulated key fibrotic markers (NF-κB p65, TGF-β1, α-SMA) and extracellular matrix accumulation.
• The combination therapy reduced inflammatory markers (MPO, differential cell count in BAL) and oxidative stress (MDA activity).
• Gene expression analysis showed downregulation of TIMP-1, MMP-2, and MMP-9, alongside upregulation of GSH, indicating enhanced antioxidative defense.

Conclusions:

• Concomitant administration of Fisetin and Pirfenidone demonstrates significant antifibrotic, antioxidative, and anti-inflammatory effects in BLM-induced pulmonary fibrosis.
• The combined therapy effectively reduces extracellular matrix deposition and improves antioxidative parameters.
• This study suggests that the PFD-FST combination is a promising therapeutic strategy for pulmonary fibrosis.