Calcium dobesilate

Calcium Dobesilate and Micro-vascular diseases

Micro-vascular diseases and its associated complications continue to be a significant health problem worldwide. Vascular lesions from microvascular involvement lead to impaired blood flow and contribute to damage and dysfunction of one or more target organs, that is, the heart, kidneys, eyes, and nervous system. Calcium Dobesilate Drug (CAD) is an established vasoactive and angioprotective drug that has shown a unique, multitarget mode of action in several experimental studies and in different animal models of diabetic microvascular complications. CAD has been widely used as an antioxidant and a vascular protective agent. At present, the application of Calcium Dobesilate is mainly related to Micro-vascular damage-related diseases, such as diabetic retinopathy (DR) and diabetic nephropathy (DN), and it is found to significantly improve the related symptoms. Its beneficial effects make it an attractive therapeutic compound especially in the early stages of these diseases. Scholars at home and abroad have studied the effectiveness, safety, and mechanisms of the related diseases, furthermore, the subjects involved patients and animal models, they have found some new clinical effects of this medicine. This paper makes a brief summary of a research progress of clinical application about Vascular injury related diseases and other aspects.

Calcium Dobesilate Restores Autophagy by Inhibiting the VEGF/PI3K/AKT/mTOR Signaling Pathway

Objective: Calcium dobesilate (CaD), an effective drug for the treatment of diabetic microvascular complications, especially diabetic retinopathy, is widely used in the clinic. Interestingly, several studies have indicated that CaD is therapeutic for diabetic kidney disease (DKD). Recently, evidence has indicated that altered vascular endothelial growth factor (VEGF) expression and decreased autophagy are the main pathological mechanisms of proteinuria. Thus, this study was conducted to explore the effect of CaD on restoring autophagy in DKD and the possible signaling pathway between VEGF and autophagy. Methods: Obese mice with spontaneous diabetes (KK-Ay) and high-fat diet- and streptozotocin-induced diabetic mice (HFD/STZ) were used in this study. Biochemical staining, western blotting, and immunohistochemistry were conducted to determine the angioprotective effect of CaD and the underlying mechanism between autophagy and VEGF/VEGFR. Results: Our results showed that CaD was capable of reducing albuminuria and restoring renal histological changes in KK-Ay and HFD/STZ-induced diabetic mice. CaD restored autophagy by decreasing the protein expression of LC3 II, Atg5, and beclin 1 and increasing the expression of P62. Moreover, CaD reduced the activation of the autophagy-related PI3K/AKT/mTOR pathway possibly via decreasing VEGF and downregulating VEGF receptor 2. Conclusion: Overall, CaD, as a novel potential therapeutic drug for DKD, plays a key role in protecting renal function and restoring autophagy by blocking VEGF/VEGFR2 and inhibiting the PI3K/AKT/mTOR signaling pathway.

[Calcium dobesilate]

Calcium dobesilate for diabetic retinopathy: a systematic review and meta-analysis

Many randomized clinical controlled trials have confirmed the efficacy and safety of calcium dobesilate in treating diabetic retinopathy (DR). This systematic review critically evaluated the evidence that links calcium dobesilate to DR. In this fixed-effects meta-analysis, a total of 221 pertinent English-language articles published between January 1975 and October 2013 were identified. Systematic searches of PUBMED, Springer Link and the Cochrane Clinical Trials Database were conducted using the keywords "diabetic retinopathy" and "calcium dobesilate". The extracted information included the study design, inclusion and exclusion criteria, setting, sample size, participant mean age, treatment regime, mean change in best corrected visual acuity, laboratory parameters, capillary fragility, intraocular pressure and fundus manifestations based on the findings of fluorescent angiography. The summary statistics indicated that calcium dobesilate was significantly associated with improving retinal microaneurysms (RR: 0.62, 95%CI: 0.42-0.90, P=0.01), retinal hemorrhages (RR: 0.39, 95% CI: 0.17-0.88, P=0.02); exudates (RR: 0.31, 95% CI: 0.12-0.81, P=0.02), reduction of whole blood viscosity (MD: -0.57 CP, 95% CI: -0.75 to -0.38, P<0.001), plasma viscosity (MD: -0.36 CP, 95% CI: -0.63 to -0.09, P=0.01) and blood cholesterol (MD: -0.48 mg mL(-1), 95% CI: -0.64-0.33, P<0.00001). Intraocular pressure was also significantly reduced (MD: -5.59 mmHg, 95% CI: -6.69 to -4.50, P<0.00001). The results indicate that calcium dobesilate effectively treats DR at the systematic and local ocular levels.

Calcium dobesilate for chronic venous insufficiency: a systematic review

Chronic venous insufficiency (CVI) causes much discomfort and sick leave. Many randomized clinical trials (RCTs) have shown a beneficial effect of calcium dobesilate, but consensus is lacking about efficacy and safety. The authors report a meta-analysis of the effectiveness and safety of calcium dobesilate in CVI. Ten RCTs (778 patients) in which calcium dobesilate for CVI was compared with placebo met the inclusion criteria. Only 3 trials (608 patients) were of good methodological quality. Calcium dobesilate significantly improved night cramps and discomfort nearly twice as well as placebo, with the number needed to treat (NNT) being 8 (95% CI 4-50) and 4 (95% CI 3-7), respectively. Frequency of adverse events was not significantly different from placebo. Subgroup analysis found a differential response with respect to disease severity, with greater improvements in pain, heaviness, and malleolar swelling being seen in the severe group than in the mild group. Calcium dobesilate improved paresthesias significantly more than placebo in the severe but not in the mild group and the effect on leg volume was also significantly better in the severe group (-7.2% vs -1.6%). No difference in effect was found for different doses of calcium dobesilate (1,000 or 1,500 mg/day). Sensitivity analyses did not affect the results. Current evidence suggests that calcium dobesilate is more effective than placebo in improving some CVI symptoms, that there is higher efficacy in more severe disease, and that a dose of 1,000 mg/day is as effective and safe as 1,500 mg/day. Further adequately powered trials are needed to further evaluate these hypotheses.