Protective Effects of a Coumarin Derivative in Diabetic Rats
作者： Claudio Bucolo , Keith W. Ward , Emanuela Mazzon , Salvatore Cuzzocrea , Filippo Drago
DOI: 10.1167/IOVS.08-3328
关键词: Peroxynitrite 、 Streptozotocin 、 Medicine 、 Enos 、 Nitric oxide synthase 、 Nitrotyrosine 、 Evans Blue 、 Internal medicine 、 Occludin 、 Diabetic retinopathy 、 Endocrinology
摘要: Purpose Retinal microvascular cells play a crucial role in the pathogenesis of diabetic retinopathy. The endothelial effects cloricromene, novel coumarin derivative, on retinopathy induced by streptozotocin (STZ) rat were investigated. Methods Cloricromene (10 mg/kg intraperitoneally) was administered daily rats, and 60 days later eyes enucleated for localization nitrotyrosine, ICAM-1, VEGF, ZO-1, occludin, claudin-5, VE-cadherin immunohistochemical analysis. effect treatment also evaluated TNFalpha, eNOS protein levels measurement retina with respective ELISA kits. Blood-retinal barrier (BRB) integrity Evans blue. Results Increased amounts cytokines, adhesion molecule, nitric oxide synthase observed retina. significantly lowered retinal eNOS. Furthermore, analysis nitrotyrosine (a marker peroxynitrite), tight junctions revealed positive staining from STZ-treated rats. degree markedly reduced tissue sections obtained rats treated cloricromene. Treatment cloricromene suppressed diabetes-related BRB breakdown 45%. Conclusions This study provides first evidence that new derivative attenuates inflammation preserving
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D. S. McLeod, G. A. Lutty, C. Merges, D. J. Lefer, Enhanced expression of intracellular adhesion molecule-1 and P-selectin in the diabetic human retina and choroid American Journal of Pathology. ,vol. 147, pp. 642- 653 ,(1995)
Aili L. Lazaar, Yassine Amrani, Reynold A. Panettieri, Up-Regulation of ICAM-1 by Cytokines in Human Tracheal Smooth Muscle Cells Involves an NF-κB-Dependent Signaling Pathway That Is Only Partially Sensitive to Dexamethasone Journal of Immunology. ,vol. 163, pp. 2128- 2134 ,(1999)
Kazuaki Miyamoto, Samer Khosrof, Sven-Erik Bursell, Yasufumi Moromizato, Lloyd Paul Aiello, Yuichiro Ogura, Anthony P. Adamis, Vascular endothelial growth factor (VEGF)-induced retinal vascular permeability is mediated by intercellular adhesion molecule-1 (ICAM-1). American Journal of Pathology. ,vol. 156, pp. 1733- 1739 ,(2000) , 10.1016/S0002-9440(10)65044-4
G. Romeo, W.-H. Liu, V. Asnaghi, T. S. Kern, M. Lorenzi, Activation of Nuclear Factor-κB Induced by Diabetes and High Glucose Regulates a Proapoptotic Program in Retinal Pericytes Diabetes. ,vol. 51, pp. 2241- 2248 ,(2002) , 10.2337/DIABETES.51.7.2241
Rachid Kacimi, Joel S. Karliner, Farid Koudssi, Carlin S. Long, Expression and Regulation of Adhesion Molecules in Cardiac Cells by Cytokines Response to Acute Hypoxia Circulation Research. ,vol. 82, pp. 576- 586 ,(1998) , 10.1161/01.RES.82.5.576
A P Adamis, Is diabetic retinopathy an inflammatory disease British Journal of Ophthalmology. ,vol. 86, pp. 363- 365 ,(2002) , 10.1136/BJO.86.4.363
Walter Fries, Emanuela Mazzon, Sergio Sturiale, Maria R Giofré, Maria A Lo Presti, Salvatore Cuzzocrea, Giuseppe M Campo, Achille P Caputi, Giuseppe Longo, Giacomo C Sturniolo, A protective effect of the synthetic coumarine derivative Cloricromene against DNB-colitis in the rat. Life Sciences. ,vol. 74, pp. 2749- 2756 ,(2004) , 10.1016/J.LFS.2003.10.016
Enrico Giraudo, Luca Primo, Enrica Audero, Hans-Peter Gerber, Pieter Koolwijk, Shay Soker, Michael Klagsbrun, Napoleone Ferrara, Federico Bussolino, None, Tumor Necrosis Factor-α Regulates Expression of Vascular Endothelial Growth Factor Receptor-2 and of Its Co-receptor Neuropilin-1 in Human Vascular Endothelial Cells Journal of Biological Chemistry. ,vol. 273, pp. 22128- 22135 ,(1998) , 10.1074/JBC.273.34.22128
Antonia M. Joussen, Vassiliki Poulaki, Wenying Qin, Bernd Kirchhof, Nicholas Mitsiades, Stanley J. Wiegand, John Rudge, George D. Yancopoulos, Anthony P. Adamis, Retinal Vascular Endothelial Growth Factor Induces Intercellular Adhesion Molecule-1 and Endothelial Nitric Oxide Synthase Expression and Initiates Early Diabetic Retinal Leukocyte Adhesion in Vivo American Journal of Pathology. ,vol. 160, pp. 501- 509 ,(2002) , 10.1016/S0002-9440(10)64869-9
J.R.S. Hoult, Miguel Payá, Pharmacological and biochemical actions of simple coumarins : Natural products with therapeutic potential General Pharmacology-the Vascular System. ,vol. 27, pp. 713- 722 ,(1996) , 10.1016/0306-3623(95)02112-4