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

• Published in: Life sciences (1973) 2023-07, Vol.324, p.121692-121692, Article 121692
• Main Authors: Abbas, Noha A.T., Nafea, Ola Elsayed, Mohammed, Heba Osama, Samy, Walaa, Abdelmageed, Amal Fawzy, Afifi, Rofaida, Hassan, Heba A.
• Format: Article
• Language: English
• Subjects: Actins - genetics; Adrenergic alpha-1 Receptor Antagonists - pharmacology; Adrenergic alpha-1 Receptor Antagonists - therapeutic use; Adrenergic beta-Agonists - pharmacology; Adrenergic beta-Agonists - therapeutic use; Animals; Bleomycin; Bleomycin-induced pulmonary fibrosis; Carvedilol; Carvedilol - pharmacology; Carvedilol - therapeutic use; Disease Models, Animal; Drug Repositioning; Gene expression; Gene Expression - drug effects; Idiopathic Pulmonary Fibrosis - drug therapy; Male; Prednisolone; Rats; Rats, Inbred Strains; Smad2 Protein - genetics; Smad2/3; Smad3 Protein - genetics; STAT3; STAT3 Transcription Factor - genetics; TGF-β; Transforming Growth Factor beta - genetics
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2023.121692

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.