calcium dobesilate
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Antioxidants ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1798
Author(s):  
Florence Njau ◽  
Hermann Haller

Monocyte-to-macrophage differentiation results in the secretion of various inflammatory mediators and oxidative stress molecules necessary for atherosclerosis pathogenesis. Consequently, this differentiation represents a potential clinical target in atherosclerosis. Calcium dobesilate (CaD), an established vasoactive and angioprotective drug in experimental models of diabetic microvascular complications reduces oxidative stress and inhibits inflammation via diverse molecular targets; however, its effect on monocytes/macrophages is poorly understood. In this study, we investigated the anti-inflammatory mechanism of CaD during phorbol 12-myristate 13-acetate (PMA)-induced monocyte-to-macrophage differentiation in in vitro models of sepsis (LPS) and hyperglycemia, using THP-1 monocytic cell line. CaD significantly suppressed CD14, TLR4, and MMP9 expression and activity, lowering pro-inflammatory mediators, such as IL1β, TNFα, and MCP-1. The effects of CaD translated through to studies on primary human macrophages. CaD inhibited reactive oxygen species (ROS) generation, PKCδ, MAPK (ERK1/2 and p38) phosphorylation, NOX2/p47phox expression, and membrane translocation. We used hydrogen peroxide (H2O2) to mimic oxidative stress, demonstrating that CaD suppressed PKCδ activation via its ROS-scavenging properties. Taken together, we demonstrate for the first time that CaD suppresses CD14, TLR4, MMP9, and signature pro-inflammatory cytokines, in human macrophages, via the downregulation of PKCδ/NADPH oxidase/ROS/MAPK/NF-κB-dependent signaling pathways. Our data present novel mechanisms of how CaD alleviates metabolic and infectious inflammation.


2021 ◽  
Author(s):  
Elham Hakimizadeh ◽  
Ayat Kaeidi ◽  
Mohammadreza Rahmani ◽  
Mohammad Allahtavakoli ◽  
Jalal Hassanshahi

Abstract Purpose: Calcium dobesilate (CaD) has antioxidant and anti-inflammatory properties. In this study, the protective effects of CaD against hepatorenal damage induced by CCL4 in male mice were evaluated. Methods: Thirty male mice randomly were divided into five groups: Control, CaD 100 mg/kg, CCL4, CCL4+CaD 50 mg/kg, and CCL4+CaD 100 mg/kg. Drugs were administered orally once a day for 4-weeks. The liver and kidney indices (serum creatinine, blood urine nitrogen, alanine aminotransferase and aspartate aminotransferase levels) were determined. Also, hepatic and renal tissue oxidant/antioxidant markers (glutathione peroxidase, malondialdehyde, total antioxidant capacity, and superoxide dismutase) were measured. Cleaved caspase-3, Bax, and Bcl-2 protein levels were measured by immunoblotting method. The liver and kidney histopathological changes were evaluated by H&E staining.Results: CCL4 induces significant oxidative stress in the kidney and liver that was concomitant with functional and histopathological abnormalities in these organs in the CCL4 group versus the control (P<0.05). CaD could significantly improve the histopathological change in the liver and kidney tissues of CCL4+CaD 100 mg/kg mice versus the CCL4 group (P<0.05). In addition, CaD attenuated apoptosis in the liver and kidney tissues (P<0.05).Conclusion: The protective effect of CaD may be related to its anti-inflammatory and antioxidant properties.


2021 ◽  
Author(s):  
Dongxuan Wang ◽  
Hui Wang ◽  
Shuang Wu ◽  
Xueqiu Yang ◽  
Jiansen Xu

Abstract Background: Calcium dobesilate (CaD) had been used in the treatment of diabetic retinopathy (DR) due to its potential in protecting against retinal vascular damage. However, it did not reduce the risk of development of diabetic macular edema (DME). The aim of this study was to investigate the effect of CaD plus intravitreal ranibizumab in the treatment of DME.Methods: This retrospective, observational, consecutive case control study enrolled patients newly diagnosed with DME who received intravitreal ranibizumab (IVR) administration with 3-monthly loading dose injection followed by pro re nata (3+PRN) regimen with or without CaD orally daily for at least 12-month follow-up. Medical records and optical coherence tomography (OCT) results were reviewed and compared at baseline and at 3, 6, and 12 months after injection.Results: A total of 102 eyes from 102 patients were enrolled in this study. Fifty-four patients received IVR combined with CaD orally (IVR+CaD group), while forty-eight patients received IVR solely (IVR group). No statistically significant differences were found in the general condition of patients between the two groups at baseline (P > 0.05). At every follow-up, 3, 6 and 12 months after injection, the best corrected visual acuity (BCVA) improved and the central macular thickness (CMT) decreased in both groups when compared with those at baseline (P < 0.05), while there were no significant differences in BCVA improvement and CMT reduction between the two groups (P > 0.05). The mean number of ranibizumab injections in R+C group was significantly lower than that in R group (5.4 ± 1.1 injections versus 6.7 ± 1.6 injections, P<0.05) within 1-year treatment. No adverse events were found in neither groups.Conclusions: Adding oral CaD to intravitreal ranibizumab was demonstrated to have similar effectiveness and safety for improving visual function and restoring the anatomy of the retina in macular with fewer injections in DME patients.


Author(s):  
Jaydeep S Chauhan ◽  
Ritika Gajre

Analytical method development and validation for estimation of Calcium Dobesilate and Docusate Sodium in Pharmaceutical dosage form with QbD approach. Combination of Calcium Dobesilate and Docusate Sodium helps for the treatment of Haemorrhoid. There is no any UV spectroscopy method of this combination due to less absorbance of the Docusate Sodium in various solvent. A specific, precise and accurate RP-HPLC method has been developed and validated for estimation of Calcium Dobesilate and Docusate Sodium in Capsule dosage form. Apply QbD approach by using statistical tool Design of experiment with Box-Behnken design for the optimization of the screening method of RP-HPLC method. Calcium Dobesilate and Docusate Sodium were estimated on Thermoscientificsyncronis C18 (250mm X 4.6mm), 5μm column using Acetonitrile: 0.01M Tetrabutylammonium dihydrogen phosphate pH-4.8(66:34, v/v) as mobile phase with flow rate 1.0 ml/min and detection was carried out at 214 nm. The retention time of Calcium Dobesilate and Docusate Sodium were found to be 2.943 min and 4.190 min respectively. The linearity and range was found to be 50-450 μg/mL for Calcium Dobesilate and 10-90μg/mL for Docusate Sodium. % RSD of precision was found to be less than 2%. %RSD for Robustness parameters was found to be less than 2%. % Recovery of Calcium Dobesilate and Docusate Sodium at different levels were found in the range of 99.451% - 100.082% and 98.071% - 101.187% respectively. So, the developed method was precise, robust and accurate. The assay value for Calcium Dobesilate and Docusate Sodium was found to be 99.772% - 99.874% and 98.159% - 98.736% respectively.


Nephron ◽  
2021 ◽  
pp. 1-15
Author(s):  
Nazma Akhter ◽  
Hong Sun ◽  
Jerrmia Ong’achwa Machuki ◽  
Hong-qi Ren

<b><i>Background:</i></b> Early acute kidney injury (AKI) predicts a high mortality rate in severely burned patients. However, the pathophysiology of early AKI induced by severe burn has not been well-defined. This study was designed to examine the protective effects of calcium dobesilate (CaD) against severe burn-induced early AKI in mice and explore the mechanism. <b><i>Methods:</i></b> The shaved backs of mice were immersed in 100°C water for 10 s to make severe burn (40% of the total body surface area). CD-57 male mice were randomly divided into sham, burn, burn + vehicle, and burn + CaD groups. Renal function, reactive oxygen species generation, tubular necrosis, and phosphorylation of mitogen-activated protein kinase, protein kinase B (Akt), and nuclear factor (NF)-κB were measured at 24 and 48 h after the burn. Renal histology, ELISA, qRT-PCR, and Western blotting were performed on the renal tissue of mice to examine the effects and mechanisms at 24 and 48 h after the burn. <b><i>Results:</i></b> Tubular damage, cast formation, and elevations of serum creatinine, BUN, and renal tissue kidney injury molecule 1 levels were all observed in the burned mice, and these were all alleviated in the mice with CaD treatment. In addition, the levels of oxidation-reduction potential and malondialdehyde were decreased, while the activities of the endogenous antioxidative enzymes were increased in the kidney tissues from the mice after CaD treatment. Furthermore, the activities of Akt, p38, extracellular sign-regulated kinase, Jun N-terminal kinase, and NF-κB signaling were increased in the kidney of burned mice and normalized after CaD treatment. <b><i>Conclusion:</i></b> This study has established, for the first time, the protective effect of CaD against early AKI in severely burned mice. CaD may exert its protective effect through alleviating oxidative stress, apoptosis, and inflammation, as well as modulating some signaling pathways in the kidney.


2021 ◽  
pp. 026835552110150
Author(s):  
Giuseppe Pompilio ◽  
Andrew Nicolaides ◽  
Stavros K Kakkos ◽  
Davide Integlia

Objective To assess the clinical efficacy of sulodexide, including a comparison with venoactive drugs (VAD) (micronized purified flavonoid fraction, MPFF; hydroxy-ethyl-rutosides, HR; calcium dobesilate;Ruscus extract combined with hesperidin methyl chalcone and vitamin C, Ruscus+HMC+VitC; horse chestnut seed extract, HCSE) and pentoxifylline in patients with chronic venous disease. Methods We performed a literature search in MEDLINE, Embase, and Cochrane Library for randomized controlled trials (RCTs) and observational studies. Proportion of patients with complete venous ulcer healing was the primary outcome and lower leg volume, foot volume, ankle circumference and symptoms were the secondary outcomes. Bayesian network meta-analysis (NMA) was perfomed with random effects models using only RCTs. A meta-analysis of observational studies was performed for sulodexide because no RCT could be included in NMA for symptoms or signs. Results Forty-five RCTs and eighteen observational studies were identified. Sulodexide was included only in a single NMA for the proportion of patients with complete ulcer healing and it showed to have the highest probability of being the best treatment (48%) compared with pentoxifylline (37%) and MPFF (16%). MPFF was the most effective treatment in reducing lower leg volume, CIVIQ-20 score and pain VAS scale while calcium dobesilate and Ruscus+HMC+VitC were the most effective in reducing foot volume and ankle circumference respectively. Meta-analyses of observational studies for sulodexide showed that it improves significantly the scoring of pain, feeling of swelling, heaviness and parasthesiae measured by Likert scales. Conclusions Sulodexide is at least as effective as pentoxifylline and more effective than MPFF in improving the rate of ulcer healing in patients with CVD. VADs are effective in improving venous symptoms and signs, as was also shown by sulodexide in the meta-analysis of observational studies. The relative effectiveness of sulodexide and VADs needs to be evaluated by an RCT in order to better inform clinical practice.


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