Idiopathic pulmonary fibrosis (IPF) is a progressive chronic interstitial lung disease of unknown origin that carries a potentially fatal prognosis. The course is usually indolent but inevitable 1;2. The disease damages mainly the alveolar epithelial cell, with increased interstitial deposition of extracellular matrix (ECM), and enhanced fibroblast/myofibroblast proliferation. It progresses to loss of respiratory function and distortion of normal lung architecture 1;3.
A variety of animal models of pulmonary fibrosis have been developed to investigate potential therapies for IPF, however, bleomycin (BLM)-induced fibrosis is the best-characterized and most prevalent model so far, studying the pathogenesis of lung fibrosis and investigating …show more content…
Numerous studies suggest that therapies targeting the ‘‘fibroproliferative’’ process and extracellular matrix accumulation may be more promising for IPF (Milam et al., 2008). During the pathogenesis of pulmonary fibrotic diseases, transforming growth factor-β (TGF-β) signaling is considered a pivotal inducer of epithelial to mesenchymal transition (EMT) and fibroblast activation, and a number of therapeutic interventions that interfere with TGF-β signaling have been developed to reverse established fibrosis. However, efficient and well-tolerated antifibrotic agents are not currently available 6 …show more content…
Drugs that inhibit 5-HT2A/2B receptors have beneficial effects in the treatment of various fibrotic disorders 7;14. Among these, terguride [1,1-diethyl-3-(6-methyl-8-ergolinyl)urea] is an ergot alkaloid derivative that acts as a potent antagonist at 5-HT2A/2B receptors 14. 01223680295
5-HT7 receptor antagonists have anti-inflammatory properties and prevents vascular remodeling and hemodynamic changes associated with pulmonary arterial hypertension (PAH) 9. However, the therapeutic potential of 5-HT7 receptor antagonists on the ‘‘fibro-proliferative’’ process and extracellular matrix accumulation in idiopathic pulmonary fibrosis has been less well studied. So, the present study was conducted to elucidate the possible anti-fibrotic effects of 5-HT7 antagonist (SB-269970) on bleomycin-induced rat pulmonary fibrosis, compared to that afforded by
A variety of animal models of pulmonary fibrosis have been developed to investigate potential therapies for IPF, however, bleomycin (BLM)-induced fibrosis is the best-characterized and most prevalent model so far, studying the pathogenesis of lung fibrosis and investigating …show more content…
Numerous studies suggest that therapies targeting the ‘‘fibroproliferative’’ process and extracellular matrix accumulation may be more promising for IPF (Milam et al., 2008). During the pathogenesis of pulmonary fibrotic diseases, transforming growth factor-β (TGF-β) signaling is considered a pivotal inducer of epithelial to mesenchymal transition (EMT) and fibroblast activation, and a number of therapeutic interventions that interfere with TGF-β signaling have been developed to reverse established fibrosis. However, efficient and well-tolerated antifibrotic agents are not currently available 6 …show more content…
Drugs that inhibit 5-HT2A/2B receptors have beneficial effects in the treatment of various fibrotic disorders 7;14. Among these, terguride [1,1-diethyl-3-(6-methyl-8-ergolinyl)urea] is an ergot alkaloid derivative that acts as a potent antagonist at 5-HT2A/2B receptors 14. 01223680295
5-HT7 receptor antagonists have anti-inflammatory properties and prevents vascular remodeling and hemodynamic changes associated with pulmonary arterial hypertension (PAH) 9. However, the therapeutic potential of 5-HT7 receptor antagonists on the ‘‘fibro-proliferative’’ process and extracellular matrix accumulation in idiopathic pulmonary fibrosis has been less well studied. So, the present study was conducted to elucidate the possible anti-fibrotic effects of 5-HT7 antagonist (SB-269970) on bleomycin-induced rat pulmonary fibrosis, compared to that afforded by