April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Calcium Dobesilate Protects Against Inflammation and Oxidative/Nitrosative Stress in the Retinas of a Diabetic Rat Model
Author Affiliations & Notes
  • Antonio F. Ambrosio
    AIBILI, Coimbra, Portugal
    Ctr Ophthalmology and Vision Sciences, IBILI, Fac Medicine, Univ Coimbra, Coimbra, Portugal
  • Paula Voabil
    AIBILI, Coimbra, Portugal
    Ctr Ophthalmology and Vision Sciences, IBILI, Fac Medicine, Univ Coimbra, Coimbra, Portugal
  • Joana Liberal
    Ctr Ophthalmology and Vision Sciences, IBILI, Fac Medicine, Univ Coimbra, Coimbra, Portugal
  • Raquel Santiago
    Ctr Ophthalmology and Vision Sciences, IBILI, Fac Medicine, Univ Coimbra, Coimbra, Portugal
  • Jacques Bauer
    OM Pharma SA, Meyrin/Geneva, Switzerland
  • Jose Cunha-Vaz
    AIBILI, Coimbra, Portugal
  • Ermelindo Leal
    AIBILI, Coimbra, Portugal
    Ctr Ophthalmology and Vision Sciences, IBILI, Fac Medicine, Univ Coimbra, Coimbra, Portugal
  • Footnotes
    Commercial Relationships  Antonio F. Ambrosio, None; Paula Voabil, None; Joana Liberal, None; Raquel Santiago, None; Jacques Bauer, OM Pharma SA (E); Jose Cunha-Vaz, OM Pharma SA (C); Ermelindo Leal, None
  • Footnotes
    Support  OM Pharma SA
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 5975. doi:
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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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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : 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.

Methods: : 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.

Results: : 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.

Conclusions: : 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.

Keywords: diabetic retinopathy • inflammation • drug toxicity/drug effects 
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