Effect of Serelaxin in Treatment of Bleomycin Induced Pulmonary Fibrosis in Rats (Serelaxin in Pulmonary Fibrosis)

Introduction: Pulmonary fibrosis is a progressive lung disorder with high mortality rate and limited successful treatment.Aim: The aim of the present study is to investigate the protective potential of serelaxin in bleomycin induced pulmonary fibrosis and to elucidate the underlying mechanisms of its action.Experimental protocol: Thirty male albino rats were categorized into 3 groups, control group (received 0.2ml saline, i.v), BLC group to induce pulmonary fibrosis (received single intravenous injection of bleomycin 120U/Kg in 0.2ml saline), serelaxin treated BLC group (following BLC injection, rats were injected i.v by serelaxin 0.5mg/kg/day for 14 days). Bronchoalveolar Lavage Fluid (BALF) and subsequent BALF analyses for total and differential cell counts. Tumor necrosis factor alpha (TNF-α), transforming growth factor beta-1 (TGFβ 1) were measured in lung homogenates. Lung collagen content was detected by measurement of lung content of hydroxyproline. Oxidative stress markers as SOD, GPx and MDA were measured in lung homogenate. Protease-anti-protease balance was detected by BALF matrix metalloproteinase-9 (mmp-9)/Tissue Inhibitor of Metalloproteinase-1 (TIMP-1) ratio. The left lung was fixed for histological examination.Results: BLC injection resulted in pulmonary inflammatory infiltration, elevated lung levels of proinflammatory and profibrotic cytokines (TNF-α and TGFβ 1 respectively) and associated oxidative stress as evidenced by decreased antioxidant enzyme level (SOD, GPx) together with increased MDA level, accumulation of collagen in lung with MMP-9/TIMP-1 imbalance, together with tissue damage shown by the histo-pathological examination. On the other hand, serelaxin treatment caused decreased pulmonary inflammatory infiltration, decreased level of TNF-α and TGFβ 1, increased levels of SOD, GPx together with decreased MDA, decreased lung collagen content and modulating MMP-9/TIMP-1 ratio.Conclusion: Serelaxin treatment may be the drug of choice in attenuating bleomycin induced pulmonary fibrosis.