IOVS
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published In Press as doi:10.1167/iovs.08-3328 on March 11, 2009
 (Investigative Ophthalmology and Visual Science. 2009;50:3846-3852.)
© 2009 by The Association for Research in Vision and Ophthalmology, Inc.
doi:10.1167/iovs.08-3328
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
iovs.08-3328v1
50/8/3846    most recent
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bucolo, C.
Right arrow Articles by Drago, F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bucolo, C.
Right arrow Articles by Drago, F.

Protective Effects of a Coumarin Derivative in Diabetic Rats

Claudio Bucolo,1 Keith W. Ward,2 Emanuela Mazzon,3 Salvatore Cuzzocrea,3,4 and Filippo Drago1

1From the Department of Experimental and Clinical Pharmacology, School of Medicine, University of Catania, Catania, Italy; 2Global Preclinical R&D Bausch & Lomb, Rochester, New York; 3IRCCS Centro Neurolesi Bonino-Pulejo, Messina, Italy; and the 4Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Messina, Italy.

PURPOSE. Retinal microvascular cells play a crucial role in the pathogenesis of diabetic retinopathy. The endothelial effects of cloricromene, a novel coumarin derivative, on diabetic retinopathy induced by streptozotocin (STZ) in the rat were investigated.

METHODS. Cloricromene (10 mg/kg intraperitoneally) was administered daily in diabetic rats, and 60 days later eyes were enucleated for localization of nitrotyrosine, ICAM-1, VEGF, ZO-1, occludin, claudin-5, and VE-cadherin by immunohistochemical analysis. The effect of treatment was also evaluated by TNF{alpha}, ICAM-1, VEGF, and eNOS protein levels measurement in the retina with the respective ELISA kits. Blood–retinal barrier (BRB) integrity was also evaluated by Evans blue.

RESULTS. Increased amounts of cytokines, adhesion molecule, and nitric oxide synthase were observed in retina. Cloricromene treatment significantly lowered retinal TNF{alpha}, ICAM-1, VEGF, and eNOS. Furthermore, immunohistochemical analysis for VEGF, ICAM-1, nitrotyrosine (a marker of peroxynitrite), and tight junctions revealed positive staining in the retina from STZ-treated rats. The degree of staining for VEGF, ICAM-1, nitrotyrosine, and tight junctions was markedly reduced in tissue sections obtained from diabetic rats treated with cloricromene. Treatment with cloricromene suppressed diabetes-related BRB breakdown by 45%.

CONCLUSIONS. This study provides the first evidence that the new coumarin derivative cloricromene attenuates the degree of inflammation preserving the BRB in diabetic rats.






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2009 by the Association for Research in Vision and Ophthalmology