Dexamethasone and losartan combination treatment protected cigarette smoke-induced COPD in rats

Abstract

Chronic Obstructive Pulmonary Disease (COPD) is a dangerous prevalent smoking-related disease characterized by abnormal inflammation and oxidative stress and expected to be the third cause of death in the world next decade. Corticosteroids have low effects in decreasing numbers of inflammatory mediators specifically in long-term use. Our study designed to investigate the possible protective effects of combined dexamethasone (Dex) (2mg/kg) and losartan (Los) (30mg/kg angiotensin receptor blocker, it possesses antioxidant and anti-inflammatory properties in lung injury in mice) against cigarette -smoke (CS) induced COPD in rats compared with dexamethasone and losartan. Male Sprague Dawley rats (N = 40) divided into five groups (n = 8): control group, CS group, Dex group, Los group, and Dex +Los group. COPD induced in rats by CS exposure twice daily for 10 weeks. After the specified treatment period, bronchoalveolar lavage fluid (BALF) and lung tissue were collected for measurement of SOD, NO, MDA, ICAM-, MMP-9, CRP, NF-κB and histopathology scoring. Our results indicated that Los+Dex significantly prevent CS-induced COPD emphysema, congested alveoli, and elevation of lung injury parameters in BALF. They also showed a significant decrease in MDA, ICAM-1, MMP-9, CRP, and NF-κB and a significant increase in SOD and NO. In conclusion, adding Los to Dex potentiating their activity in inhibition the progression of COPD based on its activity on oxidative stress, inflammation, and NF-κB protein expression.

Keywords: Chronic obstructive pulmonary disease; bronchoalveolar lavage fluid; dexamethasone; losartan.