Protective Effects of a Coumarin Derivative in Diabetic Rats

Bucolo, Claudio; Ward, Keith W.; Mazzon, Emanuela; Cuzzocrea, Salvatore; Drago, Filippo

doi:10.1167/iovs.08-3328

Cited by 52 publications

(37 citation statements)

References 28 publications

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“…Those changes include the upregulation of inducible nitric oxide synthase, cyclooxygenase -2, intercellular adhesion molecule-1 (ICAM-1), caspase-1, vascular endothelial growth factor (VEGF), and nuclear factor kappa B (NF-κB), as well as increased production of nitric oxide, prostaglandin E2, and cytokines (15,16). We and others also demonstrated that the adhesion of leukocytes to retinal vessels is increased in the retinas of diabetic animals, and this increase is correlated with changes in tight junction proteins and increased BRB permeability (4,6,8,17,18). The increase in leukostasis is also associated with an increase in the expression of ICAM-1 by retinal endothelial cells (18,19).…”

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confidence: 57%

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

et al. 2010

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OBJECTIVECalcium 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.RESEARCH DESIGN AND METHODSWistar 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.RESULTSDiabetes 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.CONCLUSIONSCaD 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.

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confidence: 57%

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

et al. 2010

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“…It is known that the activation of eNOS along with inflammatory markers contributes strongly to BRB breakdown. 39 The NO produced by eNOS is essential for the increased vascular permeability induced by VEGF. 40 In DM-SHR, there was an increase in the levels of phospho-eNOS Ser1177 (P ¼ 0.02).…”

Section: Animal Experimentsmentioning

confidence: 99%

Green Tea Is Neuroprotective in Diabetic Retinopathy

Silva

Rosales

Hamassaki‐Britto

et al. 2013

Invest. Ophthalmol. Vis. Sci.

101

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“…Retinal ischemia/reperfusion (IR) injury is involved in many ocular diseases such as ischemic optic neuropathies, diabetic retinopathy, glaucoma, and ocular ischemic syndrome, which lead to irreversible neuronal cell death [1,2,3]. Studies have presumed that oxidative stress is likely to be causally involved in IR-induced retinal damage [4,5].…”

Section: Introductionmentioning

confidence: 99%

Neuroprotective Effects of Crocin against Oxidative Stress Induced by Ischemia/Reperfusion Injury in Rat Retina

Chen

Yang

2015

Ophthalmic Res

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Aims: Crocin, a pharmacologically active component of Crocus sativus L. (saffron), has been reported to be useful in the treatment of oxidative stress injury. In the present study, we investigated the antioxidative effect of crocin and the change of the ERK signaling pathway on rat retina induced by ischemia/reperfusion (IR) injury. Methods: Crocin was pretreated 30 min before and once daily after retinal IR injury by intraperitoneal injection. The retinal morphological damage was observed by hematoxylin and eosin (HE) staining. The number of retinal ganglion cells (RGCs) was counted by Brn-3a immunofluorescence staining. The antiapoptotic effect of crocin was determined by detecting cleaved caspase-3 protein levels by means of Western blot and immunohistochemical analysis. Furthermore, retinas were also used for the determination of malondialdehyde (MDA) levels, glutathione (GSH) levels, total superoxide dismutase (T-SOD), and reactive oxygen species (ROS). The phosphorylated ERK (p-ERK) protein level was determined by Western blot and immunohistochemical analysis. Results: Our results showed that crocin treatment (50 mg/kg) significantly inhibited the decrease of retinal thickness through HE staining and protected RGCs from decreasing. Compared with the IR + vehicle group, crocin treatment significantly decreased cleaved caspase-3 and p-ERK protein expression by Western blot analysis and immunohistochemistry. Immunohistochemical staining for cleaved caspase-3 and p-ERK in the retinal sections showed positive cells were present in the RGC layer and inner nuclear layer after IR injury. Similarly, crocin (50 mg/kg) treatment also significantly increased the level of activity of GSH, enhanced the activity of T-SOD, and decreased the activity level of ROS and MDA after IR injury. Conclusions: These findings demonstrated that crocin treatment could notably protect the retina from damage induced by IR. It might be related to crocin antioxidant and antiapoptotic properties in the retina.

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Protective Effects of a Coumarin Derivative in Diabetic Rats

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

Cited by 52 publications

References 28 publications

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

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

Green Tea Is Neuroprotective in Diabetic Retinopathy

Neuroprotective Effects of Crocin against Oxidative Stress Induced by Ischemia/Reperfusion Injury in Rat Retina

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