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Calcium Dobesilate Inhibits the Alterations in Tight Junction Proteins and Leukocyte Adhesion to Retinal Endothelial Cells Induced by Diabetes

LEAL, Ermelindo C ; MARTINS, Joao ; VOABIL, Paula ; LIBERAL, Joana ; CHIAVAROLI, Carlo ; BAUER, Jacques ; CUNHA-VAZ, José ; AMBROSIO, António F

Diabetes (New York, N.Y.), 2010-10, Vol.59 (10), p.2637-2645 [Periódico revisado por pares]

Alexandria, VA: American Diabetes Association

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Calcium Dobesilate Inhibits the Alterations in Tight Junction Proteins and Leukocyte Adhesion to Retinal Endothelial Cells Induced by Diabetes
Autor: LEAL, Ermelindo C ; MARTINS, Joao ; VOABIL, Paula ; LIBERAL, Joana ; CHIAVAROLI, Carlo ; BAUER, Jacques ; CUNHA-VAZ, José ; AMBROSIO, António F
Assuntos: Animals ; Biological and medical sciences ; Blood-Brain Barrier - drug effects ; Blood-Brain Barrier - physiology ; Calcium (Nutrient) ; Calcium Dobesilate - pharmacology ; Calcium, Dietary ; Cell adhesion ; Cell Adhesion - drug effects ; Cell Adhesion - physiology ; Cell junctions ; Claudin-5 ; Complications ; Development and progression ; Diabetes ; Diabetes mellitus ; Diabetes Mellitus, Experimental - physiopathology ; Diabetes. Impaired glucose tolerance ; Diabetic Retinopathy - metabolism ; Diabetic Retinopathy - physiopathology ; Diabetic Retinopathy - prevention & control ; Endocrine pancreas. Apud cells (diseases) ; Endocrinopathies ; Endothelial Cells - cytology ; Endothelial Cells - drug effects ; Endothelial Cells - physiology ; Endothelium ; Endothelium - drug effects ; Endothelium - physiology ; Etiopathogenesis. Screening. Investigations. Target tissue resistance ; Eye and associated structures. Visual pathways and centers. Vision ; Fundamental and applied biological sciences. Psychology ; Health aspects ; Hemostatics - pharmacology ; Junctional complexes (Epithelium) ; Leukocytes ; Leukocytes - drug effects ; Leukocytes - physiology ; Male ; Medical sciences ; Membrane Proteins - drug effects ; Membrane Proteins - metabolism ; Observations ; Occludin ; Permeability - drug effects ; Phosphoproteins - drug effects ; Phosphoproteins - metabolism ; Properties ; Rats ; Rats, Wistar ; Retina - drug effects ; Retina - physiology ; Retina - physiopathology ; Tight Junctions - drug effects ; Tight Junctions - physiology ; Vertebrates: nervous system and sense organs ; White blood cells ; Zonula Occludens-1 Protein
É parte de: Diabetes (New York, N.Y.), 2010-10, Vol.59 (10), p.2637-2645
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Descrição: Calcium dobesilate (CaD) has been used in the treatment of diabetic retinopathy in the last decades, but its mechanisms of action are not elucidated. CaD is able to correct the excessive vascular permeability in the retina of diabetic patients and in experimental diabetes. We investigated the molecular and cellular mechanisms underlying the protective effects of CaD against the increase in blood-retinal barrier (BRB) permeability induced by diabetes. Wistar rats were divided into three groups: controls, streptozotocin-induced diabetic rats, and diabetic rats treated with CaD. The BRB breakdown was evaluated using Evans blue. The content or distribution of tight junction proteins (occludin, claudin-5, and zonula occluden-1 [ZO-1]), intercellular adhesion molecule-1 (ICAM-1), and p38 mitogen-activated protein kinase (p38 MAPK) was evaluated by Western blotting and immunohistochemistry. Leukocyte adhesion was evaluated in retinal vessels and in vitro. Oxidative stress was evaluated by the detection of oxidized carbonyls and tyrosine nitration. NF-κB activation was measured by enzyme-linked immunosorbent assay. Diabetes increased the BRB permeability and retinal thickness. Diabetes also decreased occludin and claudin-5 levels and altered the distribution of ZO-1 and occludin in retinal vessels. These changes were inhibited by CaD treatment. CaD also inhibited the increase in leukocyte adhesion to retinal vessels or endothelial cells and in ICAM-1 levels, induced by diabetes or elevated glucose. Moreover, CaD decreased oxidative stress and p38 MAPK and NF-κB activation caused by diabetes. CaD prevents the BRB breakdown induced by diabetes, by restoring tight junction protein levels and organization and decreasing leukocyte adhesion to retinal vessels. The protective effects of CaD are likely to involve the inhibition of p38 MAPK and NF-κB activation, possibly through the inhibition of oxidative/nitrosative stress.
Editor: Alexandria, VA: American Diabetes Association
Idioma: Inglês

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Calcium Dobesilate Inhibits the Alterations in Tight Junction Proteins and Leukocyte Adhesion to Retinal Endothelial Cells Induced by Diabetes

LEAL, Ermelindo C ; MARTINS, Joao ; VOABIL, Paula ; LIBERAL, Joana ; CHIAVAROLI, Carlo ; BAUER, Jacques ; CUNHA-VAZ, José ; AMBROSIO, António F

Alexandria, VA: American Diabetes Association

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