کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9001981 | 1118566 | 2005 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Licofelone, a novel 5-LOX/COX-inhibitor, attenuates leukocyte rolling and adhesion on endothelium under flow
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کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
داروشناسی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
The main mechanism of action of non-steroidal anti-inflammatory drugs (NSAIDs) is the inhibition of cycloxygenases COX-1 and COX-2. During recent years, combined 5-LOX/COX-inhibition, interfering with the biosynthesis of both prostaglandins and leukotrienes (LTs), has emerged as a possibility to avoid side effects related to COX-inhibition. The aim of the present study was to investigate if there is a contribution of mechanisms other than the reduction of inflammatory prostaglandins and leukotrienes to the anti-inflammatory effect of the LOX/COX inhibitor licofelone. In a flow chamber assay, licofelone (10-30 μM) dose-dependently decreased both the rolling and adhesion of leukocytes on endothelial cells (EC). In contrast, no effects were found after treatment of EC with the unselective COX-1/COX-2 inhibitor indomethacin (30 μM), the potent and selective 5-LOX inhibitor, ZD-2138 (30 μM), the mainly COX-2 inhibitor aceclofenac (30 μM), the selective COX-2 inhibitor celecoxib (30 μM) and the combination of ZD-2138 with the selective COX-2 inhibitor celecoxib (30 μM). In the presence of licofelone (30 μM) the expression of E-selectin mRNA in cytokine-stimulated EC was attenuated, whereas no NSAID (30 μM) tested showed any effect on E-selectin expression. Moreover, licofelone treatment (30 μM) attenuated expression of VCAM-1 and ICAM-1 on inflammatory EC. The effect of licofelone on leukocyte recruitment was also evaluated in vivo. Using a mouse peritonitis model it was found that leukocyte accumulation was markedly reduced in licofelone treated animals (100 mg/kg) compared to untreated mice. Thus, the novel 5-LOX/COX inhibitor licofelone possesses anti-inflammatory activity that, in addition to COX/LOX inhibition, involves effects on leukocyte-endothelial interactions.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical Pharmacology - Volume 70, Issue 1, 1 July 2005, Pages 30-36
Journal: Biochemical Pharmacology - Volume 70, Issue 1, 1 July 2005, Pages 30-36
نویسندگان
H. Ulbrich, O. Soehnlein, X. Xie, E.E. Eriksson, L. Lindbom, W. Albrecht, S. Laufer, G. Dannhardt,