Antioxidant-angioprotective actions of calcium dobesilate in diabetic rats

Hannaert, Patrick; Brunet, John; Farine, Jean-Claude; Garay, Ricardo P.

doi:10.1055/s-0031-1276203

Cited by 5 publications

(6 citation statements)

References 10 publications

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“…Although the antioxidant properties of CaD had been previously reported, 45,46 to the best of our knowledge, this is the first report in which this effect has been shown at retinal level. This is an important issue due to the pivotal role of oxidative stress in the pathogenesis of DR. 47 It has been reported that CaD protects against BRB leakage, and this effect was correlated with a decrease in the levels of VEGF in the retina.…”

Section: Discussionmentioning

confidence: 66%

Calcium Dobesilate Prevents Neurodegeneration and Vascular Leakage in Experimental Diabetes

Solà-Adell

Bogdanov

Hernández

et al. 2017

Current Eye Research

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Purpose: The mechanisms involved in the reported beneficial effects of Calcium dobesilate monohydrate (CaD) for the treatment of diabetic retinopathy (DR) remain to be elucidated. The main aim of the present study is to examine whether CaD prevents early events in the pathogenesis of DR such as neurodegeneration and vascular leakage. In addition, putative mediators of both neurodegeneration (glutamate/GLAST, ET-1/ETB receptor) and early microvascular impairment (ET-1/ETA receptor, oxidative stress, VEGF, and the PKC-delta-p38 MAPK pathway) have been examined. Methods: Diabetic (db/db) mice were randomly assigned to daily oral treatment with CaD (200 mg/Kg/ day) (n = 12) or vehicle (n = 12) for 14 days. In addition, 12 non-diabetic (db/+) mice matched by age were used as the control group. Functional abnormalities were assessed by electroretinography. Neurodegeneration and microvascular abnormalities were evaluated by immunohistochemistry and Western blot. Glutamate was determined by HPLC. Results: CaD significantly decreased glial activation and apoptosis and produced a significant improvement in the electroretinogram parameters. Mechanistically, CaD prevented the diabetes-induced upregulation of ET-1 and its cognate receptors (ETA-R and ETB-R), which are involved in microvascular impairment and neurodegeneration, respectively. In addition, treatment with CaD downregulated GLAST, the main glutamate transporter, and accordingly prevented the increase in glutamate. Finally, CaD prevented oxidative stress, and the upregulation of VEGF and PKC delta-p38 MAPK pathway induced by diabetes, thus resulting in a significant reduction in vascular leakage.Conclusions: Our findings demonstrate for the first time that CaD exerts neuroprotection in an experimental model of DR. In addition, we provide first evidence that CaD prevents the overexpression of ET-1 and its receptors in the diabetic retina. These beneficial effects on the neurovascular unit could pave the way for clinical trials addressed to confirm the effectiveness of CaD in very early stages of DR. ARTICLE HISTORY

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Section: Discussionmentioning

confidence: 66%

Calcium Dobesilate Prevents Neurodegeneration and Vascular Leakage in Experimental Diabetes

Solà-Adell

Bogdanov

Hernández

et al. 2017

Current Eye Research

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“…Some studies conducted with CD, which is classified under the venotonic and vasculoprotective agents, showed that CD has free oxygen species scavenging and decreasing properties along with the antioxidant capacity [13,14]. It increases NOS activity in macro-and microvascular endothelial cells and decreases the capillary endothelial cell desquamation depending on its effects on the NO synthesis and release [15].…”

Section: Discussionmentioning

confidence: 99%

“…However, there is no published study in the literature related to its effects on renal ischemia-reperfusion injury. In our study, we preferred a dose range of 100mg/kg/day based on a study on antioxidant and angioprotective effects of CD in diabetic rats [13].…”

Section: Discussionmentioning

confidence: 99%

Ratlarda böbrek iskemi-reperfüzyon hasarında proflaktik kalsiyum dobesilatın etkinliği

Akkoç¹,

Metin

2020

Acta Medica Alanya

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Amaç: Çalışmamızda, antioksidan ve antienflamatuvar özellikleri olduğu bilinen, kalsiyum dobesilatın deneysel böbrek iskemi-reperfüzyon hasarı (IRI) üzerindeki koruyucu etkisini araştırmayı amaçladık. Yöntemler: 24 adet erkek Wistar-Albino rat üç gruba ayrıldı; sham grubu (grup 1), iskemi-reperfüzyon grubu (grup 2) ve tedavi grubu (grup 3). İskemi-reperfüzyon işlemi öncesi Grup 3'e 10 gün boyunca 100 mg/kg/gün kalsiyum dobesilat gavaj yolu ile verildi. Sham grubu haricindeki gruplara 45 dakika iskemi ve 24 saat reperfüzyon uygulandı. Plazma üre ve kreatinin düzeyleri, eritrosit süperoksit dismutaz ve glutatyon peroksidaz enzim aktivite düzeyleri çalışıldı. Ayrıca böbrek dokusundaki iskemi-reperfüzyon hasırına ait olabilecek histopatolojik değişiklikler incelendi. Bulgular: Grup 2'de ortanca glutatyon peroksidaz ve süperoksit dismutaz enzim düzeyleri Grup 1 ve Grup 3'den daha yüksekti, ancak istatistiksel anlamlı değildi. Grup 3'de kreatinin düzeyleri Grup 1 ve Grup 2'den istatistiksel olarak anlamlı derecede daha düşüktü. Ortanca üre değerleri Grup 3'de Grup 1 ve Grup 2'den daha düşüktü ancak istatistiksel olarak anlamlı değildi. Histopatolojik incelemede; kontrol grubu ile kıyaslandığında tedavi grubunda, hücre nekrozu, tübüler epitelyal hücre düzleşmesi, sitoplazmik vakuolizasyon, tübüler lümen obstrüksiyonu ve kronik inflamasyon gibi iskemi-reperfüzyon hasarının göstergesi olan bu parametrelerin istatistiksel olarak anlamlı derecede daha az olduğu gözlendi. Sonuç: Çalışmamız, proflaktik kalsiyum dobesilatın böbrek iskemi-reperfüzyon hasarında koruyucu etkilerinin olduğunu göstermiştir.

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“…CaD has been considered as an angioprotective agent and has been shown to decrease blood viscosity and vascular permeability in patients with diabetic retinopathy [ 49 ]. In addition, it has been reported to possess antioxidant capacity that could account for reduction of vascular permeability [ 50 ]…”

Section: Cad and Diabetic Microvascular Diseasementioning

confidence: 99%

Molecular Mechanisms and Treatment Strategies in Diabetic Nephropathy: New Avenues for Calcium Dobesilate—Free Radical Scavenger and Growth Factor Inhibition

Haller

Stahl

et al. 2017

BioMed Research International

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Diabetic nephropathy is one of the most important microvascular complications of diabetes mellitus and is responsible for 40–50% of all cases of end stage renal disease. The therapeutic strategies in diabetic nephropathy need to be targeted towards the pathophysiology of the disease. The earlier these therapeutic strategies can bring about positive effects on vascular changes and prevent the vasculature in patients with diabetes from deteriorating, the better the renal function can be preserved. Studies evaluating anti-inflammatory and antioxidative strategies in diabetic nephropathy demonstrate the need and value of these novel treatment avenues. 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. On the molecular level, CaD reduces oxidative stress and inhibits growth factors such as fibroblast growth factor and vascular endothelial growth factors. Recent findings have demonstrated a strong rationale for its use in reducing urine albumin excretion rate and markers of inflammation as well as improving endothelial function. Its beneficial effects make it an attractive therapeutic compound especially in the early stages of the disease. These findings, although promising, need further confirmation in prospective clinical trials with CaD.

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Antioxidant-angioprotective actions of calcium dobesilate in diabetic rats

Cited by 5 publications

References 10 publications

Calcium Dobesilate Prevents Neurodegeneration and Vascular Leakage in Experimental Diabetes

Calcium Dobesilate Prevents Neurodegeneration and Vascular Leakage in Experimental Diabetes

Ratlarda böbrek iskemi-reperfüzyon hasarında proflaktik kalsiyum dobesilatın etkinliği

Molecular Mechanisms and Treatment Strategies in Diabetic Nephropathy: New Avenues for Calcium Dobesilate—Free Radical Scavenger and Growth Factor Inhibition

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