الفهرس 
AbstractOnly 14 pages are availabe for public view
 |  | from | 153 |  |  |
| | | from | 153 | | |
Abstract
Acute respiratory distress syndrome (ARDS) is a clinical presentation of acute lung injury (ALI) which is an inflammatory lung disease that is characterized with noncardiogenic pulmonary edema, massive lung inflammation and severe hypoxemia. Due to the limited clinical management of this disorder, ALI is among the leading causes of death in intensive care units. Dipyridamole, a coronary vasodilator drug first launched more than half a century ago, is still used as an antithrombotic and vasodilator. Ivabradine, a HR lowering agent, is used clinically to treat patients with heart failure who are intolerant of β-adrenergic receptor blockers. These drugs are of two different categories, there are now many publications describing their pleiotropic effect. The present work was aiming to evaluate the potential protective effect of Ivabradine and dipyridamole in treatment of ALI. Experimental rat model of acute lung injury was induced by intraperitoneal injection of lipo-polysaccharide (LPS) of E. coli. Thirty male Albino rats were used in the present work. The animals were divided into the following groups, the control, ALI model, ivabradine treated ALI and dipyridamole treated ALI group. At the end of the experiment body weight, lung weight and lung/body weight ratio were measured. The following parameters were measured in lung homogenates (TNF-α, IL-1β, MPO, ROS) by ELISA. Moreover, the expression of (AKT, PI3K, HMGB1, NF-κB and p38MAPK) were measured by Western blotting analysis. In addition, BALF cytological examination and histopathological examination were carried out to assess the pulmonary edema and lung injury in different studied groups. Results of the current study revealed that LPS injection in the ALI model group (group II) produced a significant increase in lung homogenate measured parameters (TNF-α, IL-1β, MPO, ROS, AKT, PI3K, HMGB1, NF-κB and p38MAPK) compared to the normal control group. BALF cytological examination and lung tissue histopathological examination showed remarkable inflammatory changes in LPS group (group II). Ivabradine administration for ALI model rats in group III produced a significant decrease in lung homogenate measured parameters (TNF-α, IL-1β, MPO, ROS, AKT, PI3K, HMGB1, NF-κB and p38MAPK) compared to the non-treated ALI model group. Lung weight and lung/Body weight ratio were non-significantly different from those of group II. Histopathological examination revealed mild alveolar edema and peri-bronchial inflammations. BALF cytological examination showed few viable inflammatory cells. Treatment of ALI model rats by dipyridamole in group III produced a significant decrease in lung weight, lung/body weight ratio and all parameters measured in lung homogenate (TNF-α, IL-1β, MPO, ROS, AKT, PI3K, HMGB1, NF-κB and p38MAPK) compared to the non-treated ALI model group. Histopathological examination revealed that the lung tissue retaining its normal state with no residual inflammations, BALF cytological examination showed minimal degenerated cells, few inflammatory cells and normal bronchial epithelial cells. Both ivabradine and dipyridamole have anti-inflammatory effect in acute lung injury. They attenuated the biochemical and molecular parameters measured in the current study. Moreover, they improved the cytological and pathological features of inflammation observed in ALI model rats. Remarkable improvement in the Dipyridamole treated group over ivabradine suggesting its stronger anti-inflammatory effect.