The antifibrotic effects of alveolar macrophages 5-HT2C receptors blockade on bleomycin-induced pulmonary fibrosis in rats

Background the most widespread chronic fibrosing lung disease is idiopathic pulmonary fibrosis. lung serotonin (5-ht) content is increased during pulmonary fibrosis with the implication of 5-ht2 receptors in the pathogenesis. serotonin plays important roles in alveolar macrophages function through 5-ht2c receptors activation. numerous studies described the important role of 5-ht2a/b receptor blockers in suppressing different types of fibrosis as idiopathic pulmonary fibrosis. the current study pointed to examine the antifibrotic effects of rs-102221 and/or terguride through in vivo model of pulmonary fibrosis. methods induction of pulmonary fibrosis was through a single dose of intra-tracheal bleomycin instillation (5 mg/kg dissolved in phosphate buffer saline) in adult male albino wistar rats. next day of bleomycin instillation,intraperitoneal injection of rs-102221 (0.5 mg/kg/d) and/or terguride (1.2 mg/kg/d) were administered and continued for 14 days. results noticeable increase in 5-ht2c receptors expression was observed in fibrotic lung tissues with marked allocation belonging to alveolar macrophages. either rs-102221 or terguride reduced the increments in lung water contents,grading of lung fibrosis,lung tumor necrosis factor-alpha (tnf-α),transforming growth factor-beta1 (tgf-β1) and vascular endothelial growth factor (vegf) levels in lung injury and fibrosis-induced by bleomycin. moreover,collagen content and myofibroblasts-alpha smooth muscle actin (α − sмa) were significantly decreased. additionally,the simultaneous administration of rs-102221 with terguride had a synergistic outcome compared to that obtained by individual monotherapy. conclusion these findings suggested the potential use of 5-ht2a/b/c antagonists as anti-fibrotic agents in lung fibrosis. © 2016