Sokar Samia S, Afify Esraa H, Osman Enass Y
Professor of Pharmacology and Toxicology, 68904Faculty of Pharmacy, Tanta University, Egypt.
68904Faculty of Pharmacy, Tanta University, Egypt.
Hum Exp Toxicol. 2021 Feb;40(2):284-296. doi: 10.1177/0960327120950012. Epub 2020 Aug 19.
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.
慢性阻塞性肺疾病（COPD）是一种危险的、与吸烟相关的常见疾病，其特征为异常炎症和氧化应激，预计在未来十年将成为全球第三大致死原因。皮质类固醇在减少炎症介质数量方面效果不佳，尤其是长期使用时。我们的研究旨在探究联合使用地塞米松（Dex）（2mg/kg）和氯沙坦（Los）（30mg/kg血管紧张素受体阻滞剂，在小鼠肺损伤中具有抗氧化和抗炎特性）与地塞米松和氯沙坦相比，对香烟烟雾（CS）诱导的大鼠慢性阻塞性肺疾病的可能保护作用。将40只雄性Sprague Dawley大鼠分为五组（每组8只）：对照组、CS组、Dex组、Los组和Dex + Los组。通过每天两次暴露于CS，持续10周诱导大鼠患慢性阻塞性肺疾病。在规定的治疗期后，收集支气管肺泡灌洗液（BALF）和肺组织，用于测量超氧化物歧化酶（SOD）、一氧化氮（NO）、丙二醛（MDA）、细胞间黏附分子-1（ICAM-1）、基质金属蛋白酶-9（MMP-9）、C反应蛋白（CRP）、核因子κB（NF-κB）并进行组织病理学评分。我们的结果表明，Los + Dex可显著预防CS诱导的慢性阻塞性肺疾病肺气肿、肺泡充血以及BALF中肺损伤参数的升高。它们还使MDA、ICAM-1、MMP-9、CRP和NF-κB显著降低，使SOD和NO显著升高。总之，基于其对氧化应激、炎症和NF-κB蛋白表达的作用，将Los添加到Dex中可增强它们抑制慢性阻塞性肺疾病进展的活性。
