الفهرس 
Chronic Obstructive Pulmonary DiseaseOnly 14 pages are availabe for public view
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Abstract
Chronic Obstructive Pulmonary Disease (COPD) is a dangerous prevalent smoking-related disease characterized by abnormal inflammation and oxidative stress and it is 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. Corticosteroids do not have a role in exacerbation even in large doses. Besides, the long term use of systematic corticosteroids can cause hypertension and other several side effects. The present study was designed to investigate the possible protective effects of ginkgo biloba (EGb761) (1mg\kg, a flavone glycoside with antioxidant and anti-inflammatory activities), losartan (Los) (30mg\kg angiotensin receptor blocker, it possesses antioxidant and anti-inflammatory properties in lung injury in mice), and their combination with dexamethasone (Dex) (2mg\kg) against cigarette -smoke (CS) induced COPD in rats compared with dexamethasone.
Male Sprague Dawley rats (N=56) were used and equally divided into seven groups (8 rats in each group); (1) control group received 0.9% saline intraperitoneal (IP) daily for ten weeks and served as control vehicle group; (2) Cigarette smoke group (CS) group received cigarette smoke, each rat exposed to 4 cigarettes at morning and 4 cigarettes afternoon for ten weeks with final concentration of 120mg tar and 8mg nicotine per day ; (3) Cigarette smoke + dexamethasone (CS+Dex) group rats were intraperitoneal injected with 2mg/kg/day dexamethasone thirty minutes before smoke exposure starting from week 6 of smoke exposure; (4) Cigarette smoke + EGb761 (CS+EGb761) group: rats will be pre-treated intraperitoneal with 1mg/kg/day ginkgo biloba thirty minutes before smoke exposure for ten weeks; (5) Cigarette smoke + dexamethasone + EGb761 (CS+Dex+EGb761) group: rats will be intraperitoneal pre-treated with 1mg/kg/day ginkgo biloba for ten weeks and they were intraperitoneal
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injected with 2mg/kg/day dexamethasone starting from week 6 of smoke exposure. Both were injected thirty minutes before smoke exposure; (6) Cigarette smoke + losartan (CS+Los) group rats will be pre-treated intraperitoneal with 30mg/kg/day losartan thirty minutes before smoke exposure for ten weeks; (7) Cigarette smoke + dexamethasone + losartan (CS+Dex+Los) group: rats will be intraperitoneal pre-treated with 30mg/kg/day losartan for ten weeks and they were intraperitoneal injected with 2mg/kg/day dexamethasone starting from week 6 of smoke exposure. Both were injected thirty minutes before smoke exposure.
After the specified treatment period, rats weighed ,anesthetized and then left lung from all rats was removed and kept in 10%neutral formalin for histopathological and NF-ĸB protein expression in lung tissue. The right lung from all rats was lavaged with sterile saline and the bronchoalveolar lavage fluid (BALF) was collected. After centrifugation, The precipitates were suspended in saline, stained with Giemsa stain solution for cell differentiation and, the supernatants were collected immediately stored for the determination of superoxide dismutase activity (SOD), malondialdehyde concentration (MDA) and nitric oxide content (NO), matrix metalloproteinase 9 (MMP-9), intracellular adhesion molecule (ICAM-1) and C-reactive protein (CRP).
Results of this investigation showed that CS exposure produced significant increases in numbers of macrophages and lymphocytes, MDA, MMP-9, ICAM-1 and CRP in BALF as well as NF-ĸB expression, and necrosis and inflammation scores in lung tissue with a significant reduction in percentage of viable cells, SOD and NO levels in BALF compared with control group. On the other hand, rats received ginkgo biloba, losartan and\or dexamethasone concomitantly with CS produced significant decreases in numbers of macrophages and lymphocytes, MDA, MMP-9, ICAM-1 and CRP in BALF as well as as NF-ĸB expression, and necrosis
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and inflammation scores in lung tissue with a significant elevation in percentage of viable cells, SOD and NO levels in BALF compared with CS group.
These observations revealed that ginkgo biloba and losartan alone or in combination with dexamethasone have protective effects against COPD induced by cigarette smoke. In addition, the combination of ginkgo biloba or losartan with dexamethasone produced augmented anti-inflammatory and anti-oxidant effects against the progression of COPD. The use of combination can decrease doses of corticosteroids, accordingly decrease the side effects of corticosteroids. Thus, this combined therapy may represent a possible new therapeutic strategy against COPD in humans.