The Potential Role of Serelaxin in Cigarette Smoke-Induced Chronic Obstructive Pulmonary Disease in Adult Male Rats (Serelaxin in COPD)
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- Category: Vol. 84, June 2016
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The Potential Role of Serelaxin in Cigarette Smoke-Induced Chronic Obstructive Pulmonary Disease in Adult Male Rats (Serelaxin in COPD), REHAB E. ABO EL-GHEIT
Abstract
Introduction: Chronic Obstructive Pulmonary Disease (COPD) is a prevalent smoking-related disease for which no disease altering therapies currently exist. Serelaxin, a recom-binant form of human gene-2 relaxin, rhRLX, has now estab-lished as a pleiotropic hormone with significant therapeutic and clinical implications.
Aim: We explored the curative and/or preventive effects and molecular mechanisms of serelaxin treatment in Chronic Cigarette Smoke (CS) induced pulmonary injury in COPD rat model.
Experimental protocol: COPD was induced by whole-body exposure to CS for 12 week. The COPD rats were treated with either serelaxin (0.5mg/kg/day) or vehicle. Serelaxin was administered either on the first day of CS exposure (preventive mode) or at the end of fourth week of CS exposure (therapeutic mode), till the end of experimental period. 40 male albino rats were randomized into control, COPD, thera-peutic serelaxin and preventive serelaxin COPD treated groups. The control normal group was exposed to ambient air and vehicle treated. Bronchoalveolar Lavage Fluid (BALF) and subsequent BALF analyses for total protein content, total and differential cell counts were performed on the right lung together with the lung Wet-to-Dry (W/D) weight ratio, Tumor Necrosis Factor Alpha (TNF-a) to evaluate CS-induced lung inflammation, whereas the left lung was fixed for the histo-logical assessment. Lung collagen content was analyzed by hydroxyproline assay. While lung 4-Hydroxy-2-Nonenal (4- HNE) and Total Antioxidant Capacity (TAC), were measured as oxidative stress biomarkers. Extent of emphysema was assessed by urinary desmosine (DES) level, while the protease-antiprotease imbalance was assessed by the BALF Matrix Metalloproteinase-9 (MMP-9)/Tissue Inhibitor of Metallopro-teinase-1 (TIMP-1) ratio. Fulton's index and pulmonary vessel Wall Thickness (WT) were used to asses Pulmonary Arterial Hypertension (PAH).
Results: Chronic CS exposure caused pulmonary inflam-matory infiltration, increased lung vascular permeability, elevated lung levels of proinflammatory cytokine, TNF-a and oxidative stress as evidenced by increased 4-HNE with reduced TAC and increased urinary DES, lung collagen deposition with MMP-9/TIMP-1 imbalance, together with tissue damage shown by the histo-pathological examination.
Serelaxin treatment of COPD rats, blocked, at early, and attenuated, at established, phases of COPD, the smoking-induced pulmonary injury, airway and Pulmonary Artery (PA) remodeling by suppressing the ongoing inflammatory process in the smoked lungs, mitigates the associated small air ways fibrosis, increasing anti-oxidant capacity and modulating the MMP-9/TIMP-1 levels in a rat model of smoke-induced COPD. So Serelaxin treatment can prevent and reverse the development of COPD and PH in CS rats.
Conclusion: Serelaxin treatment could be target as a new promising therapy in COPD and its associated PH.