Calcium dobesilate reduces endothelin-1 and high-sensitivity C-reactive protein serum levels in patients with diabetic retinopathy.
(12/16)
PURPOSE: To determine the benefits of calcium dobesilate (CaD) administration on endothelial function and inflammatory status in patients with diabetic retinopathy through measurement of serum levels of endothelin-1 and high-sensitivity C-reactive protein (hsCRP). METHODS: In a double-blind, randomized clinical trial, 90 patients with either severe nonproliferative or proliferative diabetic retinopathy and with blood glucose level of 120-200 mg/dl were randomly allocated to treatment with either CaD tablets (500 mg daily) or placebo for 3 months. Visual acuity, intraocular pressure, and macular status were performed before the study. The serum levels of endothelin-1 and hsCRP were evaluated in both groups before and at the third month of the trial. RESULTS: The median serum level of hsCRP significantly differed between the groups 3 months following the CaD or placebo administration (2.2 mg/l in the CaD group versus 3.7 mg/l in the placebo group, p=0.01). The mean endothelin-1 serum level was 0.69+/-0.32 pg/ml in the CaD group and 0.86+/-0.30 pg/ml in the placebo group (p=0.01). Furthermore, in the CaD group, the serum levels of both endothelin-1 and hsCRP were significantly decreased 3 months after administration of CaD (p<0.001). CONCLUSIONS: Administration of the CaD in the patients with diabetic retinopathy may reduce the serum levels of endothelin-1 and hsCRP. This might imply amelioration of the endothelial function and inflammatory status following CaD therapy in these patients. (+info)
Can calcium dobesilate be used safely for peripheral microvasculopathies that require neoangiogenesis?
(13/16)
Effects of calcium dobesilate on the synthesis of endothelium-dependent relaxing factors in rabbit isolated aorta.
(14/16)
1. Some cardiovascular disturbances which occur in diabetics are a consequence of alterations in vascular contractility as well as in endothelium-dependent relaxation. 2. Calcium dobesilate (DOBE) is a drug used in diabetic retinopathy and its mechanism of action is not yet understood. 3. The aim of this study was to investigate the effects of DOBE on synthesis and release of endothelium-dependent relaxing factor (EDRF) and endothelium-dependent hyperpolarizing factor (EDHF) in rabbit isolated aorta. 4. Endothelium-dependent relaxation induced by acetylcholine (ACh) (10(-8)-(10(-5) M) increased in the presence of DOBE 10(-5) M only when vascular endothelium was kept intact. 5. NG-nitro-L-arginine methyl ester (L-NAME; 10(-8)-10(-4) M progressively decreased the enhancing effect of DOBE on endothelium-dependent relaxation whereas it was progressively increased by L-Arg. 6. DOBE 10(-5) M increased in a non-significant manner endothelium-dependent relaxation induced by ACh when the arteries were incubated with both L-NAME 10(-4) M and indomethacin 10(-5) M. 7. DOBE (10(-6) M and 10(-5) M) was able to scavenge superoxide anion radicals generated by the hypoxanthine/xanthine oxidase reaction. 8. These results provide evidence that DOBE is able to affect the vascular disorders associated with diabetes mellitus since it enhances the synthesis of endothelium-dependent relaxing factors. (+info)
Dobesilate enhances endothelial nitric oxide synthase-activity in macro- and microvascular endothelial cells.
(15/16)
1. Dobesilate is used for normalizing vascular dysfunction in a number of diseases. In search for an effect on endothelial NO production, macrovascular endothelial cells from rat aorta, microvascular endothelial cells from rat exocrine pancreatic tissue, and capillary endothelial cells from rat islets, were cultured in the presence or absence of Mg-Dobesilate. The activity of constitutive nitric oxide synthase (ecNOS) in resident cells as well as of inducible nitric oxide synthase (iNOS) in cytokine-activated cells was measured indirectly by recording the citrulline concentrations in culture supernatants. 2. In each of the different endothelial cells Mg-Dobesilate incubation (0.25-1 mM) for 24 h led to a significant and concentration-dependent increase in ecNOS-activities. With cytokine-activated endothelial cell cultures only moderate effects were seen with little or no concentration-dependency. Addition of the NOS-inhibitor N(G)-monomethyl-L-arginine led to a significant suppression of citrulline formation in all cultures as an evidence for the enzyme specificity of these effects. 3. iNOS- and ecNOS-specific reverse transcription and semi-quantitative polymerase chain reaction (RT-PCR) with RNA from resident or cytokine-activated endothelial cells gave no evidence for an increase in NOS-specific mRNA after Mg-Dobesilate-treatment. Furthermore, Dobesilate-mediated enhancement of NO synthesis in resting endothelial cells was not due to iNOS induction in these cells, as no iNOS-specific signal was found by RT-PCR. (+info)
In vitro effects of calcium dobesilate on the responsiveness of spontaneously diabetic rat aorta.
(16/16)
We tested the effect of calcium dobesilate (DOBE) in aorta from spontaneously diabetic (BB/wor) rats. The contraction induced by 10(-6) M noradrenaline (NA) in BB/wor rats was smaller than that induced in control rats (1.21+/-0.11 vs 0.82+/-0.02 g, P<0.01, n=8, respectively) in arteries with intact endothelium. Incubation with DOBE (10(-4) M) impaired the contractions induced by NA in BB/wor rats (1.21+/-0.11 vs 0.67+/-0.01 g, P<0.01, n=8). The effect of DOBE was reversed by 10(-6) M propranolol (0.67+/-0.01 vs 1.20+/-0.60g, P<0.001, n=8, with 10(-4) M DOBE and 10(-4)M DOBE plus 10(-6) M propranolol, respectively). DOBE increased the endothelium-dependent relaxation in arteries from diabetic rats. These findings suggest that DOBE might improve vascular reactivity in BB/wor rats. (+info)