Article

Calcium dobesilate in the treatment of diabetic retinopathy.

Equipe d'Accueil EA2381, Laboratoire Pharmacologie Transports Ioniques Membranaires, Université Paris 7, Paris, France.
Treatments in Endocrinology 02/2005; 4(4):221-32. pp.221-32
Source: PubMed

ABSTRACT The incidence of diabetic retinopathy is still increasing in developed countries. Tight glycemic control and laser therapy reduce vision loss and blindness, but do not reverse existing ocular damage and only slow the progression of the disease. New pharmacologic agents that are currently under development and are specifically directed against clearly defined biochemical targets (i.e. aldose reductase inhibitors and protein kinase C-beta inhibitors) have failed to demonstrate significant efficacy in the treatment of diabetic retinopathy in clinical trials. In contrast, calcium dobesilate (2,5-dihydroxybenzenesulfonate), which was discovered more than 40 years ago and is registered for the treatment of diabetic retinopathy in more than 20 countries remains, to our knowledge, the only angioprotective agent that reduces the progression of this disease. An overall review of published studies involving calcium dobesilate (CLS 2210) depicts a rather 'non-specific' compound acting moderately, but significantly, on the various and complex disorders that contribute to diabetic retinopathy. Recent studies have shown that calcium dobesilate is a potent antioxidant, particularly against the highly damaging hydroxyl radical. In addition, it improves diabetic endothelial dysfunction, reduces apoptosis, and slows vascular cell proliferation.

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    Article: Effects of stobadine and vitamin E in diabetes-induced retinal abnormalities: involvement of oxidative stress
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    ABSTRACT: ARCMED-D-06-00499). Background. Because hyperglycemia-induced oxidative stress may be a cause of retinop-athy, this study examined the hypothesis that administration of exogenous antioxidants, sto-badine (ST) and vitamin E (vitE), can restore retinal abnormalities in experimental diabetes. Methods. Normal and streptozotocin (STZ)-induced male Wistar rats received daily in-traoral doses of ST (24.7 mg/kg) and vitE (a-dl-tocopherol acetate, 400e500 IU/kg) in-dividually or in combinations for 8 months. The biochemical parameters including aldose reductase enzyme (AR) activity and lipid peroxidation (MDA), and histopathological changes such as retinal capillary basement membrane thickness (RCBMT) and vascular endothelial growth factor (VEGF) expression were evaluated. Results. A 37.99% increase in RCBMT was observed in rats after 8 months diabetes du-ration. The increase in RCBMT was 12.34% in diabetic rats treated with ST and 23.07% in diabetic rats treated with vitE. In diabetic rats treated with antioxidant combination, just a 4.38% increase was observed in RCBMT. The excess VEGF immunoreactivity and increased MDA and AR activity determined in diabetic retina were significantly at-tenuated by individual antioxidant treatments. Although both antioxidants decreased blood glucose, HbA1c, fructosamine and triglyceride levels in diabetic rats, poor glyce-mic control was maintained in all experimental groups during the treatment period. How-ever, the antioxidant combination led to almost complete amelioration in retinal MDA and RCBMT in diabetic rats. Conclusions. The ability of antioxidant combination to arrest retinal abnormalities and lipid peroxidation even in the presence of poor glycemic control might advocate the key role of direct oxidative damage and the protective action of antioxidants in retinal alterations associated with diabetic retinopathy. Ó 2007 IMSS. Published by Elsevier Inc.
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    Article: Oxidative stress and diabetic retinopathy.
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    ABSTRACT: Oxygen metabolism is essential for sustaining aerobic life, and normal cellular homeostasis works on a fine balance between the formation and elimination of reactive oxygen species (ROS). Oxidative stress, a cytopathic consequence of excessive production of ROS and the suppression of ROS removal by antioxidant defense system, is implicated in the development of many diseases, including Alzheimer's disease, and diabetes and its complications. Retinopathy, a debilitating microvascular complication of diabetes, is the leading cause of acquired blindness in developed countries. Many diabetes-induced metabolic abnormalities are implicated in its development, and appear to be influenced by elevated oxidative stress; however the exact mechanism of its development remains elusive. Increased superoxide concentration is considered as a causal link between elevated glucose and the other metabolic abnormalities important in the pathogenesis of diabetic complications. Animal studies have shown that antioxidants have beneficial effects on the development of retinopathy, but the results from very limited clinical trials are somewhat ambiguous. Although antioxidants are being used for other chronic diseases, controlled clinical trials are warranted to investigate potential beneficial effects of antioxidants in the development of retinopathy in diabetic patients.
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  • Article: Effects of stobadine and vitamin E in diabetes-induced retinal abnormalities: involvement of oxidative stress.
    [show abstract] [hide abstract]
    ABSTRACT: Because hyperglycemia-induced oxidative stress may be a cause of retinopathy, this study examined the hypothesis that administration of exogenous antioxidants, stobadine (ST) and vitamin E (vitE), can restore retinal abnormalities in experimental diabetes. Normal and streptozotocin (STZ)-induced male Wistar rats received daily intraoral doses of ST (24.7 mg/kg) and vitE (alpha-dl-tocopherol acetate, 400-500 IU/kg) individually or in combinations for 8 months. The biochemical parameters including aldose reductase enzyme (AR) activity and lipid peroxidation (MDA), and histopathological changes such as retinal capillary basement membrane thickness (RCBMT) and vascular endothelial growth factor (VEGF) expression were evaluated. A 37.99% increase in RCBMT was observed in rats after 8 months diabetes duration. The increase in RCBMT was 12.34% in diabetic rats treated with ST and 23.07% in diabetic rats treated with vitE. In diabetic rats treated with antioxidant combination, just a 4.38% increase was observed in RCBMT. The excess VEGF immunoreactivity and increased MDA and AR activity determined in diabetic retina were significantly attenuated by individual antioxidant treatments. Although both antioxidants decreased blood glucose, HbA1c, fructosamine and triglyceride levels in diabetic rats, poor glycemic control was maintained in all experimental groups during the treatment period. However, the antioxidant combination led to almost complete amelioration in retinal MDA and RCBMT in diabetic rats. The ability of antioxidant combination to arrest retinal abnormalities and lipid peroxidation even in the presence of poor glycemic control might advocate the key role of direct oxidative damage and the protective action of antioxidants in retinal alterations associated with diabetic retinopathy.
    Archives of Medical Research 08/2007; 38(5):503-11. · 1.88 Impact Factor

Keywords

'non-specific' compound
 
20 countries
 
angioprotective agent
 
apoptosis
 
biochemical targets
 
calcium dobesilate
 
countries
 
damaging hydroxyl radical
 
diabetic endothelial dysfunction
 
diabetic retinopathy
 
glycemic control
 
laser therapy
 
New pharmacologic agents
 
ocular damage
 
potent antioxidant
 
progression
 
protein kinase C-beta inhibitors
 
reverse
 
significant efficacy
 
vision loss