Idiopathic pulmonary fibrosis (IPF) is believed to be an epithelial-fibroblast disease. Activated epithelial cells are thought to release potent fibrogenic molecules and cytokines, such as tumor necrosis factor-alpha (TNF-α) and transforming growth factor-beta1 (TGF-β1), which in turn foster the transformation of fibroblasts into myofibroblasts and promote production of extracellular matrix molecules and so collagen deposition. Serotonin (5-hydroxy tryptamine, 5-HT) is an important mediator for lung fibrogenesis, with implication of 5-HT2A/B/C receptors. However, the antifibrotic effects of all 5-HT2 receptor subtypes versus 5-HT2A/C blockade is needing to be explored. So, the present study was conducted to evaluate the antifibrotic effects of mirtazapine (5-HT2A/C receptor blocker) and cyproheptadine (5-HT2A/B/C receptor blocker) on body weight changes, survival rates, the lung hydroxyproline and TGF-β1 levels as well as the histopathological changes of lung fibrosis, in bleomycin-induced rat pulmonary fibrosis. Eighty-eight adult rats were used and subdivided randomly into 11 groups. One normal control, five vehicle control groups and five groups with IPF that induced by intra-tracheal instillation of bleomycin alone (5mg/kg), or bleomycin and treated with either mirtazapine (15 mg/kg/day) or cyproheptadine (5 mg/kg/day) for 7 and 14 days. Oral treatment with either mirtazapine or cyproheptadine, significantly ameliorated losses in body weights, reduction in survival rates, lung hydroxyproline and TGF-β1 levels and the inflammatory effects in lungs induced by bleomycin. The mechanisms underlying these therapeutic effects could be dependent on the reduction of TGF-β1 actions as decreasing lung inflammation and production and deposition of collagen in fibrotic lung tissues.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.