Repurposing of carvedilol to alleviate bleomycin-induced lung fibrosis in rats: Repressing of TGF-β1/α-SMA/Smad2/3 and STAT3 gene expressions.

Abstract

Idiopathic pulmonary fibrosis (IPF) is the most widely studied interstitial lung disease. IPF eventually leads to respiratory insufficiency, lung cancer, and death. Carvedilol (CAR) is a third-generation β-adrenergic receptor antagonist with an α1-blocking effect. CAR demonstrates antifibrotic activities in various experimental models of organ fibrosis.

AIMS:

This work is designed to explore the possible alleviating effects of CAR on bleomycin (BLM)-induced lung fibrosis in rats.

MAIN METHODS:

The BLM rat model of lung fibrosis was achieved by intratracheal delivery of a single dose of 5 mg/kg of BLM. Seven days following BLM injection, either prednisolone or CAR was orally administered at doses of 10 mg/kg once daily for 21 days to the rats. The actions of CAR were evaluated by lung oxidant/antioxidant parameters, protein concentration and total leucocyte count (TLC) in bronchoalveolar lavage fluid (BALF), fibrosis regulator-related genes along with the coexistent lung histological changes.

KEY FINDINGS:

CAR effectively decreased lung malondialdehyde level, increased superoxide dismutase activity, declined both protein concentration and TLC in BALF, downregulated TGF-β1/α-SMA/Smad2/3 and STAT3 gene expressions, and repaired the damaged lung tissues.

SIGNIFICANCE:

CAR conferred therapeutic potential against BLM-induced lung fibrosis in rats, at least in part, to its antioxidant, anti-inflammatory, and antifibrotic activities. CAR could be utilized as a prospective therapeutic option in patients with lung fibrosis in clinical practice.

• Authors: Noha A T Abbas, Ola Elsayed Nafea, Heba Osama Mohammed, Walaa Samy, Amal Fawzy Abdelmageed, Rofaida Afifi, Heba A Hassan
• Journal: Life sciences (Life Sci) Vol. 324 Pg. 121692 (Jul 01 2023) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 37061127 (Publication Type: Journal Article)
• Copyright: Copyright © 2023 Elsevier Inc. All rights reserved.

Chemical References

• Bleomycin
• Carvedilol
• Adrenergic alpha-1 Receptor Antagonists
• Adrenergic beta-Agonists
• Transforming Growth Factor beta
• Acta2 protein, rat
• Smad2 Protein
• Smad3 Protein
• STAT3 Transcription Factor
• Actins

Topics

• Bleomycin
• Carvedilol (pharmacology, therapeutic use)
• Drug Repositioning
• Animals
• Rats
• Idiopathic Pulmonary Fibrosis (drug therapy)
• Adrenergic alpha-1 Receptor Antagonists (pharmacology, therapeutic use)
• Adrenergic beta-Agonists (pharmacology, therapeutic use)
• Gene Expression (drug effects)
• Transforming Growth Factor beta (genetics)
• Smad2 Protein (genetics)
• Smad3 Protein (genetics)
• STAT3 Transcription Factor (genetics)
• Actins (genetics)
• Disease Models, Animal
• Male
• Rats, Inbred Strains