Calcium Dobesilate Prevents Neurodegeneration and Vascular Leakage in Experimental Diabetes (original) (raw)
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Diabetes/Metabolism Research and Reviews, 2004
Background Diabetic retinopathy (DR) is a highly specific vascular complication of type 1 and type 2 diabetes mellitus. Calcium dobesilate (DOBE) has been tested in the treatment of diabetic retinopathy showing a slowdown of the progression of the disease after long-term oral treatment. The aim of this study was to determine the effects of DOBE on vascular and diabetic retinopathy in streptozotocin (STZ) diabetic rats. Methods Diabetes was induced in wistar rats by the administration of STZ (60 mg/kg, i.p.). Rats were divided into three groups (n = 30). Group 0 (GO): nondiabetic rats. Group 1 (G1): 14 months of insulin treatment after diabetes development. Group 2 (G2): 14 months of insulin treatment after diabetes development plus DOBE (500 mg/kg/day). At the end of the treatment, vascular reactivity was tested. The study of the vascularization of the retina was performed on wholemounts of trypsin retinal digest preparations and retinal sections. Results Relaxation induced by acetylcholine decreased in the aorta arteries from diabetic rats but it was restored to control values in the DOBEtreated group (71.8 ± 4.5%, 53.3 ± 0.5%, 67.4 ± 4.6% in group 0, 1 and 2 respectively). DOBE treatment also restored noradrenaline (1.08 ± 0.05 g, 1.70 ± 0.08 g, 1.13 ± 0.05 g in group 0, 1 and 2 respectively) and caffeineinduced contractions. Diabetic state did not cause any alteration in mesenteric arteries. The analysis of the retinal digests showed vascular tortuosity, acellular capillaries, focal accumulations of capillaries and reduction of the number of pericytes in G1. The vascular changes observed in G2 seem to be intermediate between the control and the diabetic rats. Conclusions We showed that long-term treatment with DOBE attenuated the progression of diabetic retinopathy and the alterations in vascular reactivity in streptozotocin-induced diabetic rats.
Antioxidant properties of calcium dobesilate in ischemic/reperfused diabetic rat retina
European Journal of Pharmacology, 2001
Calcium dobesilate possesses antioxidant properties and protects against capillary permeability by reactive oxygen species in the rat peritoneal cavity, but whether a similar action can take place in the diabetic rat retina is unknown. We investigated the oral treatment of diabetic rats with calcium dobesilate on the prevention of free radical-mediated retinal injury induced by ischemia/reperfusion (90 min ischemia followed by 3 min and/or 24 h of reperfusion). Streptozotocin-induced diabetic rats were orally treated with 50 and 100 mg/kg of calcium dobesilate for 10 days (n=12 in each group). In the first series of studies, calcium dobesilate was found to significantly reduce the maldistribution of ion content in diabetic ischemic/reperfused rat retina. Thus, in diabetic rats treated with 100 mg/kg/day calcium dobesilate, ischemia/reperfusion provoked: (i) 27.5% increase in retinal Na(+) content compared to 51.8% in the vehicle-treated group (P<0.05), and (ii) 59.6% increase in retinal Ca(2+) content compared to 107.1% in vehicle-treated animals (P<0.05). In the second series of studies, calcium dobesilate was found to significantly protect diabetic rat retina against inhibition of Na(+)/K(+)-ATPase and Ca(2+)/Mg(2+)-ATPase activities by ischemia/reperfusion (54% and 41% reduction, respectively, with 100 mg/kg of calcium dobesilate) and also against changes in retinal ATP, reduced glutathione (GSH), and oxidized glutathione (GSSG) contents. In the third series of experiments, rats treated with 100 mg/kg of calcium dobesilate reduced the hydroxyl radical signal intensity to 41% (measured by electron paramagnetic resonance), induced by ischemia/reperfusion in diabetic rat retina. Finally, 100 mg/kg calcium dobesilate significantly reduced retinal edema (measured by the thickness of the inner plexiform layer) in diabetic rats. In conclusion, oral treatment with calcium dobesilate significantly protected diabetic rat retina against oxidative stress induced by ischemia/reperfusion. Whether the antioxidant properties of calcium dobesilate explain, at least in part, its beneficial therapeutic effects in diabetic retinopathy deserves further investigation.
BJSTR, 2022
Early detection of lesions and maintenance of the normal functioning of the retinal tissue at an early stage of non-proliferative diabetic retinopathy (NPDR) is considered an extremely important step in its secondary prevention, which makes it advisable to include angioprotective drugs in the complex of conservative therapy. One of the drugs of interest is “Doxy-Chem” - (calcium dobesilate) a drug that improves retinal microcirculation, is able to prevent and correct biochemical changes in nerve tissues and has an endothelioprotective effect.
The Effect of Calcium Dobesilate on Nonproliferative Diabetic Retinopathy: A Controlled Study
Ophthalmology, 1978
Two independent, double-masked, controlled studies were made to evaluate the efficacy of calcium dobesilate for the treatment of nonproliferative diabetic retinopathy. Forty-two patients underwent a six-month crossover evaluation while receiving calcium dobesilate (750 mg per day) and placebo in random order. Thirty-six patients received calcium dobesilate (1,000 mg per day) or placebo for one year. Evaluation by clinical examination, fluorescein angiography, and fundus photography failed to demonstrate any beneficial effect of calcium dobesilate.
Inhibition of choroidal angiogenesis by calcium dobesilate in normal Wistar and diabetic GK rats
European Journal of Pharmacology, 2005
Calcium dobesilate reduces vascular endothelial growth factor (VEGF) over-expression in diabetic rat retina, but its effect on intraocular angiogenesis is unknown. Therefore, we tested calcium dobesilate for its in vitro and ex vivo effects on choroidal explant angiogenesis in spontaneously diabetic Goto-Kakizaki (GK) rats. Choroidal explants were cultured in gels of collagen. Budded microvessels numbers and VEGF formation were taken as markers of angiogenesis. Ex vivo studies were performed in GK rats orally given 100 mg/kg/day calcium dobesilate for 10 days. In vitro, calcium dobesilate dose-and time-dependently inhibited both microvessel formation and VEGF production, at concentrations z25 Ag/ml (i.e. z60 AM), with complete inhibition at 100 Ag/ml. Oral treatment of diabetic GK rats with calcium dobesilate induced a significant reduction of choroidal angiogenesis ex vivo (38.8% after 3 days of culture). In conclusion, calcium dobesilate inhibited choroidal explant angiogenesis both in vitro and ex vivo. This effect may be due, at least in part, to inhibition of VEGF production. Antiangiogenesis by calcium dobesilate can be involved in its therapeutic benefit in diabetic retinopathy.