PURPOSE: Pulmonary fibrosis is a devastating disease with a poor prognosis. Although the diagnosis and pathophysiology of this disease have been better characterized over the past few years, there is no effective therapy for the disease. The aim of this study was to evaluate the anti-inflammatory and anti-fibrotic effects of sirolimus (SRL), which is a potential anti-fibrotic agent, by using bleomycin (BLM)-induced pulmonary fibrosis model in rats. METHODS: A single intra-tracheal injection of BLM (2.5 U/kg) was administered and sirolimus (2.5 mg/kg/day) was given orally, beginning either one day before (early SRL) or nine days after (late SRL) the BLM administration. The effect of SRL on fibrosis was studied by analysis of cytokine levels in BAL fluid, measurement of lung tissue hydroxyproline (HPL) content and histopathological examination. RESULTS: Both early and late SRL administrations caused a decrease in the levels of IL-13, PDGF-A and TGF-β1 (p=0.001) and an increase in IFN-γ levels (p=0.001) in BAL fluid. Early and late SRL also caused a decrease in HPL content (p=0.001). Early sirolimus caused a significant decrease in fibrosis score (p=0.001), while late SRL did not. CONCLUSION: Sirolimus was effective in BLM-induced pulmonary fibrosis model, especially in the early phases of the disease.
PURPOSE:Pulmonary fibrosis is a devastating disease with a poor prognosis. Although the diagnosis and pathophysiology of this disease have been better characterized over the past few years, there is no effective therapy for the disease. The aim of this study was to evaluate the anti-inflammatory and anti-fibrotic effects of sirolimus (SRL), which is a potential anti-fibrotic agent, by using bleomycin (BLM)-induced pulmonary fibrosis model in rats. METHODS: A single intra-tracheal injection of BLM (2.5 U/kg) was administered and sirolimus (2.5 mg/kg/day) was given orally, beginning either one day before (early SRL) or nine days after (late SRL) the BLM administration. The effect of SRL on fibrosis was studied by analysis of cytokine levels in BAL fluid, measurement of lung tissue hydroxyproline (HPL) content and histopathological examination. RESULTS: Both early and late SRL administrations caused a decrease in the levels of IL-13, PDGF-A and TGF-β1 (p=0.001) and an increase in IFN-γ levels (p=0.001) in BAL fluid. Early and late SRL also caused a decrease in HPL content (p=0.001). Early sirolimus caused a significant decrease in fibrosis score (p=0.001), while late SRL did not. CONCLUSION:Sirolimus was effective in BLM-induced pulmonary fibrosis model, especially in the early phases of the disease.
Authors: Avignat S Patel; Ling Lin; Alexander Geyer; Jeffrey A Haspel; Chang Hyeok An; Jiaofei Cao; Ivan O Rosas; Danielle Morse Journal: PLoS One Date: 2012-07-18 Impact factor: 3.240
Authors: Guadalupe Tirma González-Mateo; Anna Rita Aguirre; Jesús Loureiro; Hugo Abensur; Pilar Sandoval; José Antonio Sánchez-Tomero; Gloria del Peso; José Antonio Jiménez-Heffernan; Vicente Ruiz-Carpio; Rafael Selgas; Manuel López-Cabrera; Abelardo Aguilera; Georgios Liappas Journal: Biomed Res Int Date: 2015-11-25 Impact factor: 3.411