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Antonio F. Ambrosio, Paula Voabil, Joana Liberal, Raquel Santiago, Jacques Bauer, Jose Cunha-Vaz, Ermelindo Leal; Calcium Dobesilate Protects Against Inflammation and Oxidative/Nitrosative Stress in the Retinas of a Diabetic Rat Model. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5975.
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Diabetic retinopathy is a leading cause of vision loss and acquired blindness in working-age adults in developed countries. Calcium dobesilate (CaD) is a synthetic benzene sulfonate derivative used in the treatment of diabetic retinopathy. It has been shown to correct the excessive vascular permeability in the retina of diabetic patients and in experimental diabetes. However, the mechanisms underlying its protective effects are not completely elucidated. The beneficial effects of CaD may be related to its antioxidant properties or to an inhibition of inflammatory processes, which are considered to play a key role in the breakdown of the blood-retinal barrier (BRB). Therefore, the main goal of the present study was to evaluate and clarify the effect of CaD on the inflammation and oxidative/nitrosative stress induced by diabetes in the retina.
Wistar rats were divided into four groups: controls, diabetic rats (2 month diabetes duration), diabetic rats treated with CaD (100 mg/kg/day; given orally, during the last 2 weeks of the 2-month diabetes duration) and non-diabetic rats treated with CaD for two weeks. The expression of pro-inflammatory cytokines, namely interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), was evaluated by RT-PCR and western blotting. Oxidative/nitrosative stress was evaluated by the detection of oxidized carbonyl groups by dot blot and nitrated tyrosine residues by immunohistochemistry.
The expression levels of the pro-inflammatory cytokines IL-1β and TNF-α were elevated in the retinas of diabetic animals, and CaD was able to prevent the increase of these pro-inflammatory cytokines. As expected, diabetes also increased the oxidative/nitrosative stress in the retina. The formation of oxidized carbonyl residues and the immunoreactivity against nitrotyrosine, particularly in the ganglion cell layer, significantly increased in the retina of diabetic rats, and these effects were prevented by CaD.
These results show that CaD is able to inhibit oxidative/nitrosative stress and inflammation induced by diabetes in the retina, suggesting that the protective effects of CaD appear undeniably related to its antioxidant properties. This is the first study demonstrating that CaD inhibits the production of pro-inflammatory cytokines in the retina.
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