Can calcium dobesilate be used safely for peripheral microvasculopathies that require neoangiogenesis?

Demirtaş, Sinan; Çalışkan, Ahmet; Güçlü, Orkut; Yazici, Suleyman; Karahan, Oğuz; Yavuz, Celal; Mavitaş, Binali

doi:10.12659/msmbr.889427

Cited by 8 publications

(5 citation statements)

References 15 publications

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“…To the best of the authors' knowledge, the current study is the first to demonstrate that CaD inhibits changes in endothelial and inflammatory protein levels. Specifically, CaD significantly inhibited the expression of VEGF and VEGFR, which are known to mediate abnormal HUVEC proliferation ( 17 ). CaD also prevented the HG-induced increases in HUVEC migration and permeability, most likely by suppressing ICAM-1, PTX3 and MCP-1 expression.…”

Section: Discussionmentioning

confidence: 99%

Calcium dobesilate may alleviate diabetes-induced endothelial dysfunction and inflammation

Zhou

Yuan

Chen

et al. 2017

Molecular Medicine Reports

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Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease. However, the pathogenesis of DKD remains unclear, and no effective treatments for the disease are available. Thus, there is an urgent need to elucidate the pathogenic mechanisms of DKD and to develop more effective therapies for this disease. Human umbilical vein endothelial cells (HUVECs) were cultured using different D-glucose concentrations to determine the effect of high glucose (HG) on the cells. Alternatively, HUVECs were incubated with 100 µmol/l calcium dobesilate (CaD) to detect its effects. The authors subsequently measured HUVEC proliferation via cell counting kit-8 assays. In addition, HUVEC angiogenesis was investigated via migration assays and fluorescein isothiocyanate (FITC)-labelled bovine serum albumin (BSA) permeability assays. The content or distribution of markers of endothelial dysfunction [vascular endothelial growth factor (VEGF), VEGF receptor (R) and endocan) or inflammation [intercellular adhesion molecule (ICAM)-1, monocyte chemotactic protein (MCP)-1 and pentraxin-related protein (PTX3)] was evaluated via reverse transcription-quantitative polymerase chain reaction and western blotting. HG treatment induced increased in VEGF, VEGFR, endocan, ICAM-1, MCP-1 and PTX3 mRNA and protein expression in HUVECs. HG treatment for 24 to 48 h increased cell proliferation in a time-dependent manner, but the cell proliferation rate was decreased at 72 h of HG treatment. Conversely, CaD inhibited abnormal cell proliferation. HG treatment also significantly enhanced HVUEC migration compared to the control treatment. In contrast, CaD treatment partially inhibited HUVEC migration compared to HG exposure. HG-treated HUVECs exhibited increased FITC-BSA permeability compared to control cells cultured in medium alone; however, CaD application prevented the HG-induced increase in FITC-BSA permeability and suppressed HG-induced overexpression of endothelial markers (VEGF, VEGFR-2, endocan) and inflammation markers (ICAM-1, MCP-1, PTX3) in HUVECs. CaD has angioprotective properties and protects endothelial cells partly by ameliorating HG-induced inflammation. The current results demonstrated the potential applicability of CaD to the treatment of diabetic nephropathy, particularly during the early stages of this disease.

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Section: Discussionmentioning

confidence: 99%

Calcium dobesilate may alleviate diabetes-induced endothelial dysfunction and inflammation

Zhou

Yuan

Chen

et al. 2017

Molecular Medicine Reports

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“…In addition, CaD abrogates choroidal angiogenesis both in vitro and ex vivo in a dose-dependent manner [87]. Furthermore, Demirtas et al [88] have shown in a chick chorioallantoic membrane model that CaD has a potent antiangiogenic effect with a dose-dependent action.…”

Section: Calcium Dobesilatementioning

confidence: 99%

Non-Traditional Systemic Treatments for Diabetic Retinopathy: An Evidence-Based Review

Simó

Ballarini²,

Cunha‐Vaz³

et al. 2015

CMC

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Abstract:The rapid escalation in the global prevalence diabetes, with more than 30% being afflicted with diabetic retinopathy (DR), means it is likely that associated vision-threatening conditions will also rise substantially. This means that new therapeutic approaches need to be found that go beyond the current standards of diabetic care, and which are effective in the early stages of the disease. In recent decades several new pharmacological agents have been investigated for their effectiveness in preventing the appearance and progression of DR or in reversing DR; some with limited success while others appear promising. This up-to-date critical review of non-traditional systemic treatments for DR is based on the published evidence in MEDLINE spanning 1980-December 2014. It discusses a number of therapeutic options, paying particular attention to the mechanisms of action and the clinical evidence for the use of renin-angiotensin system blockade, fenofibrate and calcium dobesilate monohydrate in DR.

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“…The evaluation of angiogenesis was evaluated according to surrounding capillary density (as described previously) and the antiangiogenic scores were determined according to scoring system that described in previous literature. [12][13][14] The Scoring System Normal capillary development: score 0 (Figure 1A)…”

Section: Arrangement Of the Chorioallantoic Membrane (Cam)mentioning

confidence: 99%

Investigation of the Antiangiogenic Properties of Zoledronic Acid by Using Chorioallantoic Membrane Model

Gülcü

Akkaya

2022

Dose-Response

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Objective Zoledronic acid (ZA) is a bisphosphonate-derived agent used in osteoporotic clinical pathologies to prevent the development of complications such as fractures and hypercalcemia by regulating bone metabolism. Studies have been conducted on the antiangiogenic efficacy of this agent, which also has other systemic side effects. In this study, the dose-dependent antiangiogenic activity of ZA was investigated on the chorioallantoic membrane model (CAM). Methods Three doses (10−4, 10−5, and 10−6 M concentrations) of drug pellets were prepared with ZA and another pellet was prepared as the positive control group with vascular endothelial growth factor (VEGF) inhibitor agent bevacizumab (10−6 M concentration). Thereafter all pellets were placed on chorioallantoic membranes on the fourth day of egg incubation. All eggs were evaluated for capillary development four days after the drug application. Results The highest antiangiogenic effect was detected in the positive control group. Moreover, incremental antiangiogenic effects were detected with average scores of .9, 1.1, 1.2 in 10−6, 10−5, and 10−4 M concentrations of ZA groups respectively. Conclusion Our findings supported that ZA has dose-dependent antiangiogenic effects. This result suggests that different dosing may be required in cases where angiogenesis is therapeutic.

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Can calcium dobesilate be used safely for peripheral microvasculopathies that require neoangiogenesis?

Cited by 8 publications

References 15 publications

Calcium dobesilate may alleviate diabetes-induced endothelial dysfunction and inflammation

Calcium dobesilate may alleviate diabetes-induced endothelial dysfunction and inflammation

Non-Traditional Systemic Treatments for Diabetic Retinopathy: An Evidence-Based Review

Investigation of the Antiangiogenic Properties of Zoledronic Acid by Using Chorioallantoic Membrane Model

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