Repurposing of carvedilol to alleviate bleomycin-induced lung fibrosis in rats: Repressing of TGF-ß1/α-SMA/Smad2/3 and STAT3 gene expressions.
Life Sci
; 324: 121692, 2023 Jul 01.
Article
em En
| MEDLINE
| ID: mdl-37061127
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 ß-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. MAINMETHODS:
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. KEYFINDINGS:
CAR effectively decreased lung malondialdehyde level, increased superoxide dismutase activity, declined both protein concentration and TLC in BALF, downregulated TGF-ß1/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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Expressão Gênica
/
Agonistas Adrenérgicos beta
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Fibrose Pulmonar Idiopática
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Antagonistas de Receptores Adrenérgicos alfa 1
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Reposicionamento de Medicamentos
/
Carvedilol
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Life Sci
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Egito