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At least 19 recordsLinked to original sources
PubMed1998

In vitro antioxidant properties of calcium dobesilate.

Calcium dobesilate, a vascular protective agent, was tested in vitro for its scavenging action against oxygen free radicals. Calcium dobesilate was as potent as rutin to scavenge hydroxyl radicals (IC50 = 1.1 vs 0.7 microM, respectively). It was also able to scavenge superoxide radicals, but with 23 times less potency than rutin (IC50 = 682 vs 30 microM, respectively). Calcium dobesilate significantly reduced platelet activating factor (PAF)-induced chemiluminescence in human PMN cells and lipid peroxidation by oxygen free radicals in human erythrocyte membranes, although these actions required calcium dobesilate concentrations > or = 50 microM. Finally, in cultured bovine aortic endothelial cells, magnesium dobesilate reduced the increase in cytosolic free calcium induced by hydrogen peroxide and inhibited phenazine methosulfate-induced cell potassium loss. In conclusion, calcium dobesilate was effective in scavenging hydroxyl radicals in vitro, at therapeutically relevant concentrations. Conversely, higher concentrations of the compound were required to scavenge superoxide radicals or to protect the cells against the deleterious effects of intracellular reactive oxygen species. Further studies in vivo are required to determine if these antioxidant properties of calcium dobesilate can play a role in its vascular protective mechanisms.

Animals↗
PubMed1987

[Modification of eicosanoid synthesis by calcium dobesilate].

Calcium dobesilate is a vasoactive drug with well-known effects on endothelial integrity, vascular wall permeability and blood viscosity. A clinical study demonstrated that serum thromboxane formation is significantly decreased by calcium dobesilate in patients suffering from peripheral vascular disease. Hence an in vitro study has been undertaken to determine the influence of calcium dobesilate on eicosanoid formation both by platelets and the arterial wall. Radio-thin-layer chromatography (RTLC) of human platelets does not show any influence of the drug on eicosanoid conversion in a dose range from 10 to 1000 micrograms/ml. By contrast, the vascular conversion of eicosanoids shows a dose-dependent trend towards a decrease in cyclooxygenase products. However, using the same doses, no effect is observed on vascular PGI2 formation in vitro, as assessed by means of the platelet aggregation bioassay and thus no inhibitory effect on cyclooxygenase of the arterial wall can be deduced. These laboratory findings provide no explanation for the clinical efficacy of calcium dobesilate and the diminution in serum thromboxane. A different mode of metabolic conversion of endogenous and exogenous arachidonic acid is suggested as explanation for these contradictory results.

Arachidonic Acid↗
PubMed1999

Antioxidant-Angioprotective Actions of Calcium Dobesilate in Diabetic Rats.

Calcium dobesilate was tested in rats with streptozotocin(STZ)-induced diabetes, for its angioprotective properties against the extravasation of plasma Evans blue towards the peritoneal cavity, induced in situ by the free radical generating agent phenazine methosulfate (PMS). In diabetic rats pretreated with a single oral dose of 50 and 200 mg/kg calcium dobesilate, PMS-induced Evans blue extravasation was respectively reduced by 60 and 100% with respect to values in vehicle-treated animals (p < 0.05 and p < 0.01 respectively; in diabetic rats, PMS-induced Evans blue peritoneal extravasation was double as in control animals = 0.0814 +/- 0.019 vs. 0.0396 +/- 0.0083 h-1, p < 0.05). In diabetic rats pretreated with 50 and 100 mg/kg/day of calcium dobesilate for 7 days, PMS-induced Evans blue extravasation was respectively reduced by 56 and 80% with respect to values in vehicle-treated animals (p < 0.01 and p < 0.001 respectively). In conclusion, calcium dobesilate p.o. significantly and dose-dependently antagonized the increase in capillary permeability induced by an oxidative stress in the peritoneal cavity of diabetic rats. These results further suggest that the antioxidant properties of calcium dobesilate can be involved, at least in part, in its angioprotective actions in humans.

Journal Article↗
PubMed1989

Inhibition of sorbitol formation in human erythrocytes by calcium dobesilate.

The effects of calcium dobesilate (Doxium, a drug already known to prevent or reverse the retinal microvascular lesions of diabetes mellitus) on sorbitol formation in human erythrocytes was studied, and compared with the effects of tetramethylene glutaric acid (TMGA), a specific aldose reductase inhibitor. Both compounds inhibited sorbitol formation. In a 29 mmol/l glucose medium, calcium dobesilate in concentrations of 2 and 10 mmol/l caused, 50 and 100% inhibition of sorbitol formation, respectively, whereas TMGA completely inhibited sorbitol formation at a concentration of 0.1 mmol/l. These results suggest that calcium dobesilate may exert, at least in part, its beneficial effect on diabetic microangiopathy by inhibiting the formation of sorbitol. The inhibition of sorbitol synthesis may be mediated by an inhibitory action of calcium dobesilate on aldose reductase.

Aldehyde Reductase↗
PubMed2004

Safety of calcium dobesilate in chronic venous disease, diabetic retinopathy and haemorrhoids.

The aim of the present review is to consider the adverse effects and the safety profile of calcium dobesilate. Calcium dobesilate (Doxium) is a veno-tonic drug, which is widely prescribed in more than 60 countries from Europe, Latin America, Asia and the Middle East for three main indications: chronic venous disease, diabetic retinopathy and the symptoms of haemorrhoidal attack. Data sources used for this review comprise the international literature (1970-2003), a postmarketing surveillance (PMS) report for calcium dobesilate from OM Pharma (Geneva, Switzerland) covering the period 1974-1998, and periodic safety update reports (PSUR) covering the period 1995-2003 from the French Regulatory authorities pharmacovigilance database and OM Pharma. Data from the PMS report for 1974-1998 indicated that adverse events with calcium dobesilate did not occur very frequently and had the following distribution in terms of frequency: fever (26%), gastrointestinal disorders (12.5%), skin reactions (8.2%), arthralgia (4.3%), and agranulocytosis (4.3%). No deaths were attributed to calcium dobesilate in the PMS report. Using data on product use in the Swiss Compendium we estimated the prevalence of agranulocytosis to be 0.32 cases/million treated patients, i.e. ten times less than the calculated prevalence of agranulocytosis in the general population. Most adverse events are type B, i.e. rare and unrelated to the pharmacological properties of calcium dobesilate. This review concludes that the risk of an adverse effect with calcium dobesilate 500-1500 mg/day is low and constant over time. The recently raised problem of agranulocytosis (a total of 13 known cases drawn from all data sources) appears to be related to methodological bias. Such a review reinforces the need for a strong international pharmacovigilance organisation using similar methods to detect and analyse the adverse effects of drugs.

Animals↗
PubMed2001

Antioxidant properties of calcium dobesilate in ischemic/reperfused diabetic rat retina.

Calcium dobesilate possesses antioxidant properties and protects against capillary permeability by reactive oxygen species in the rat peritoneal cavity, but whether a similar action can take place in the diabetic rat retina is unknown. We investigated the oral treatment of diabetic rats with calcium dobesilate on the prevention of free radical-mediated retinal injury induced by ischemia/reperfusion (90 min ischemia followed by 3 min and/or 24 h of reperfusion). Streptozotocin-induced diabetic rats were orally treated with 50 and 100 mg/kg of calcium dobesilate for 10 days (n=12 in each group). In the first series of studies, calcium dobesilate was found to significantly reduce the maldistribution of ion content in diabetic ischemic/reperfused rat retina. Thus, in diabetic rats treated with 100 mg/kg/day calcium dobesilate, ischemia/reperfusion provoked: (i) 27.5% increase in retinal Na(+) content compared to 51.8% in the vehicle-treated group (P<0.05), and (ii) 59.6% increase in retinal Ca(2+) content compared to 107.1% in vehicle-treated animals (P<0.05). In the second series of studies, calcium dobesilate was found to significantly protect diabetic rat retina against inhibition of Na(+)/K(+)-ATPase and Ca(2+)/Mg(2+)-ATPase activities by ischemia/reperfusion (54% and 41% reduction, respectively, with 100 mg/kg of calcium dobesilate) and also against changes in retinal ATP, reduced glutathione (GSH), and oxidized glutathione (GSSG) contents. In the third series of experiments, rats treated with 100 mg/kg of calcium dobesilate reduced the hydroxyl radical signal intensity to 41% (measured by electron paramagnetic resonance), induced by ischemia/reperfusion in diabetic rat retina. Finally, 100 mg/kg calcium dobesilate significantly reduced retinal edema (measured by the thickness of the inner plexiform layer) in diabetic rats. In conclusion, oral treatment with calcium dobesilate significantly protected diabetic rat retina against oxidative stress induced by ischemia/reperfusion. Whether the antioxidant properties of calcium dobesilate explain, at least in part, its beneficial therapeutic effects in diabetic retinopathy deserves further investigation.

Adenosine Triphosphate↗
PubMed1985

Effect of calcium dobesilate and its interaction with aspirin on thrombus formation in vivo.

The effect of calcium dobesilate (calcium dihydroxy-2,5 benzenesulphonate) on thrombus formation in vivo was evaluated. Experimental thrombi were induced in a venule of a hamster cheek pouch following iontophoresis of adenosine diphosphate (ADP). Calcium dobesilate administered intraperitoneally as a single injection inhibited thrombus formation in a time- and dose-dependent manner. Furthermore, the combination of calcium dobesilate and aspirin resulted in the potentiation of the inhibition of thrombus formation.

Animals↗
PubMed2004

Reduction of retinal albumin leakage by the antioxidant calcium dobesilate in streptozotocin-diabetic rats.

Calcium dobesilate stabilizes blood-retinal barrier in patients with diabetic retinopathy and possesses antioxidant properties in the retinas of rats with streptozotocin-induced diabetes, exposed ex vivo to ischemia-reperfusion. Here we investigated the action of calcium dobesilate on retinal albumin leakage in streptozotocin-diabetic rats, together with relevant in vivo retinal antioxidant and permeability markers, i.e., carboxymethyl-lysine-advanced glycation end product (CML-AGE) formation and vascular endothelial cell growth factor (VEGF) overexpression. Twenty days after streptozotocin administration, diabetic rats were treated for 10 days with calcium dobesilate (100 mg/kg/day per os) or vehicle. Retinal albumin leakage, CML-AGE formation, and VEGF overexpression were evaluated by immunohistochemistry of frozen eye sections. Diabetic rats exhibited dramatic increases in: (i) retinal albumin leakage (31% of positive vessels vs. 0.2% in nondiabetic rats, P<0.008), (ii) CML-AGE retinal occurrence (40+/-3% vs. undetectable positive vessels), and (iii) retinal VEGF protein expression (14.6+/-1.1 vs. 3.5+/-0.5 VEGF-positive spots/field, P<10(-4)). Calcium dobesilate significantly reduced: (i) retinal albumin leakage (by 70%, P<0.008), (ii) retinal CML-AGEs contents (by 62%, P<0.008), and (iii) retinal VEGF expression (by 69.4%, P<0.008). In conclusion, calcium dobesilate orally given to diabetic rats markedly reduced retinal hyperpermeability, CML-AGE contents, and VEGF overexpression. These results strongly suggest that calcium dobesilate stabilizes blood-retinal barrier in diabetic retinopathy via an in situ antioxidant action. Further studies in patients are required to confirm such view.

Albumins↗
PubMed2005

Inhibition of choroidal angiogenesis by calcium dobesilate in normal Wistar and diabetic GK rats.

Calcium dobesilate reduces vascular endothelial growth factor (VEGF) over-expression in diabetic rat retina, but its effect on intraocular angiogenesis is unknown. Therefore, we tested calcium dobesilate for its in vitro and ex vivo effects on choroidal explant angiogenesis in spontaneously diabetic Goto-Kakizaki (GK) rats. Choroidal explants were cultured in gels of collagen. Budded microvessels numbers and VEGF formation were taken as markers of angiogenesis. Ex vivo studies were performed in GK rats orally given 100 mg/kg/day calcium dobesilate for 10 days. In vitro, calcium dobesilate dose- and time-dependently inhibited both microvessel formation and VEGF production, at concentrations >or=25 mug/ml (i.e. >or=60 microM), with complete inhibition at 100 microg/ml. Oral treatment of diabetic GK rats with calcium dobesilate induced a significant reduction of choroidal angiogenesis ex vivo (38.8% after 3 days of culture). In conclusion, calcium dobesilate inhibited choroidal explant angiogenesis both in vitro and ex vivo. This effect may be due, at least in part, to inhibition of VEGF production. Antiangiogenesis by calcium dobesilate can be involved in its therapeutic benefit in diabetic retinopathy.

Animals↗
PubMed1999

Prevention of Oxidation and Apoptosis in Human Peripheral Blood Mononuclear Cells Exposed to Calcium Dobesilate.

The antioxidant effects of calcium dobesilate (CD) (Doxium(R)) were investigated in relation to the oxidative status, apoptosis, and in vitro proliferation of human peripheral blood mononuclear cells (PBMC) isolated from healthy donors. Calcium dobesilate alone did not modify cell growth in vitro until it reached 10 µM. This molecule counteracted oxidative damage generated by the highly reducing sugar 2-deoxy-D-ribose (dR) and was shown to reduce apoptosis by delaying both membrane permeability changes and DNA fragmentation. Calcium dobesilate (10 µM) was effective in a time-dependent manner on several parameters, representative of the cellular oxidative status. In particular, CD significantly increased the activity of glutathione S-transferase (GST) after 3 days of treatment and also the activity of gamma-glutamyltransferase (gamma-GT). Both of these enzymes are known to be involved in the glutathione (GSH) metabolic cycle. This enzymatic behavior was reversed after 7 days of treatment, with a significant GST decrease and a gamma-GT activation. After 7 days of CD exposure, the intracellular GSH content was enhanced and this resulted in a dramatic decrease of lipid peroxidation, underlining the powerful antioxidant properties of CD in human PBMC.

Journal Article↗
PubMed1998

Calcium dobesilate: pharmacology and future approaches.

1. Calcium dobesilate (2,5-dihydroxybenzene sulfonate) is a drug commonly used in the treatment of diabetic retinopathy and chronic venous insufficiency. 2. The pharmacology of calcium dobesilate reveals its ability to decrease capillary permeability, as well as platelet aggregation and blood viscosity. 3. Furthermore, recent data show that calcium dobesilate increases endothelium-dependent relaxation owing to an increase in nitric oxide synthesis.

Animals↗
PubMed1998

Angioprotective action of calcium dobesilate against reactive oxygen species-induced capillary permeability in the rat.

Calcium dobesilate possesses antioxidant properties in vitro, but the in vivo significance and putative angioprotective role of these properties are undefined. Here, calcium dobesilate was tested in a newly developed in vivo model of microvascular permeabilization induced by reactive oxygen species in the rat peritoneal cavity. In this model, microvascular permeabilization is equated to the rate of Evans blue extravasation toward the peritoneal cavity. Basal Evans blue extravasation (rate constant values ke = 0.0176 +/- 0.0015 h-1) was markedly and significantly increased by reactive oxygen species generated in situ, with: (i) phenazine methosulfate/NADH (delta ke(phenazine methosulfate) = 0.0419 +/- 0.0043 h-1) and (ii) xanthine/xanthine oxidase (delta ke(xo) = 0.0383 +/- 0.0010x h-1). These actions of reactive oxygen species were abolished by locally injected superoxide dismutase (i.p., 300 units/kg). Intraperitoneally given calcium dobesilate (100 mg/kg) inhibited 75-100% of reactive oxygen species-induced Evans blue extravasation. By the intravenous route, calcium dobesilate i.v. (1-50 mg/kg) dose dependently inhibited phenazine methosulfate-induced Evans blue extravasation with an ID50 of 2-5 mg/kg (full inhibition was reached at 20-50 mg/kg). After single oral administration, calcium dobesilate (5-500 mg/kg) dose dependently inhibited phenazine methosulfate-dependent Evans blue extravasation with an ID50 of 50-100 mg/kg (81% inhibition at 500 mg/kg, P < 0.003). After 7 days of oral calcium dobesilate (50 mg/kg once/day) phenazine methosulfate-induced Evans blue peritoneal extravasation was significantly reduced by half. These effects of calcium dobesilate were similar to those observed with a comparative antioxidant molecule, rutin. In conclusion, rat peritoneal microvascular permeability was strongly increased by reactive oxygen species, an effect that was significantly reduced by intraperitoneal, intravenous and oral calcium dobesilate. These results support the hypothesis that the antioxidant properties of calcium dobesilate could play a role in its angioprotective properties in vivo.

Administration, Oral↗
PubMedDate not supplied

[Effectiveness and innocuousness of the association of calcium dobesilate, dexamethasone acetate and lidocaine versus prednisolone capronate with dibucaine clorohydrate in the treatment of hemorrhoids-].

The objective of the present study was to compare properties of two associations in the topical treatment of hemorrhoids. They were included 40 patient with diagnosis of internal hemorrhoids grade 1 or 2, which was indicated topic treatment after the realization of an interrogatory and anoscopy. The treatment received according to a randomized and double blind design: A = dobesilate of calcium with acetato of dexamethasone and lidocaine or B = Capronato of Prednisolone with Clorhidrato of dibucaina, applied twice a day. They were carried out controls every 7 days. In each control was carried out interrogatory and respective anoscopy. There was a prevalence of the females, and the age corresponded to the 5t decade of the life. Patients of the treatment. A presented greater number of predisponents factors, but minor percentage of previous treatments. As for the evaluation of the punctuation of symptoms and of the grade of Hemorrhoids, comparing beginning and final, they didn't show significant difference interproduct confirming the effectiveness and similar inocuity. In both products was observed a important improvement concerning to the symptoms and grade of hemorrhoids but the patients of the treatment A precipitated the greater speed. As for the evaluation made by the phisicians, the treatment A (88%) and B (85.7%) the got successful outputs. The opinion of the patients was a 100% of marked goods or moderated beneficial. Both treatments were successful so much in effectiveness like in inocuity although the treatment A were always got the best efectiveness outputs.

Administration, Topical↗
PubMedDate not supplied

Pharmacokinetics of calcium dobesilate in beagle dogs after repeated administration.

Many pharmacological findings suggest that repeated intravenous administration of calcium dobesilate improves myocardial lymphatic drainage, accelerates removal of degradation products and other toxic substances by increasing the number of functioning lymphatics and thus limits infarct size after experimental coronary artery occlusion. The aim of the present study was to investigate the relationship between the blood levels of calcium dobesilate and the pharmacological effect described above using the same dosage schedule. During the first six hours after intravenous administrations, at one hour interval, of three doses each of 100 mg/kg of calcium dobesilate, the average plasma level ranged from 414 micrograms/ml to 95 micrograms/ml with a plateau between the second and fourth hour. During this period, which is the most crucial for the ischemic myocardium, the effect of calcium dobesilate attained its optimum as evidenced by a statistically significant increase in the number of lymphatics visualized by lymphangiography and the reduction of infarct size measured by planimetry, by weight or by tomography. The plasma levels before the 18th hour were still higher than 10 micrograms/ml but no measurable calcium dobesilate was detected in the plasma at the 20th hour which indicates total elimination of the drug from the blood and thus precluding any risk of accumulation. The present results confirm that the doses of calcium dobesilate used in the pharmacological studies correspond to an adequate blood level.

Animals↗
PubMed1990

Drug-induced fever: a clinical report and challenge test with calcium dobesilate.

A 54-year-old man was receiving calcium dobesilate for retinopathy and after 8 days he presented fever of more than 39 degrees C, generalized myalgia, chills and headache. Other causes of fever were ruled out. A challenge test was done with a single therapeutic oral dose of calcium dobesilate and fever appeared 20 h later and lasted 8 h. Our patient fulfils Young's stringent criteria for drug fever. To our knowledge drug-induced fever due to calcium dobesilate has not been reported previously.

Calcium Dobesilate↗
PubMedDate not supplied

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.

Calcium Dobesilate↗
PubMed2002

Calcium dobesilate ameliorates lung injury following lower limb ischemia/reperfusion.

We examined the effects of calcium dobesilate on ameliorating the lung damage following ischemia-reperfusion injury in skeletal muscle of rats. A well known antioxidant, dimethyl sulfoxide, was also tested for comparison. The study included three groups: normal saline, dimethyl sulfoxide and calcium dobesilate. Plasma bicarbonate, creatine kinase, lactate dehydrogenase, thiobarbituric acid reactive substances (TBARS), as well as muscle and lung tissue TBARS levels were measured. Lung tissue samples were taken for histological examination. The dimethyl sulfoxide group showed significant amelioration of plasma (p = 0.004), skeletal muscle (p = 0.006) and lung TBARS (p = 0.004) levels, compared with controls. Calcium dobesilate-treated rats showed significantly low level muscle (p = 0.025) and lung TBARS (p = 0.004), compared with the control group. The extent of lung injury according to the histological findings was less in the dimethyl sulfoxide (p = 0.004) and calcium dobesilate (p = 0.003) groups. These observations indicated that calcium dobesilate acted effectively in the prevention of lung damage following ischemia-reperfusion injury in the rat skeletal muscle.

Animals↗
PubMed1990

Myocardial infarction treated with two lymphagogues, calcium dobesilate (CLS 2210) and hyaluronidase: a coded, placebo-controlled animal study.

The effects on the evolution of canine myocardial infarction (MI) of the lymphagogues hyaluronidase (hyaluronate glucanohydrolase) (known to reduce the size of MIs) and calcium dobesilate (calcium, 2,5-dihydroxybenzenesulfonate, CLS 2210) were compared in a coded, placebo-controlled study in 48 dogs, during the first 24 h after coronary occlusion. MI was induced by embolization of the anterior descending branch of the left coronary artery. The animals were given either a placebo, CLS 2210, or hyaluronidase by intravenous infusion begun immediately after embolization and continued for 24h. The volume of myocardial tissue at risk was evaluated at 2 and 24 h by ungated computed tomography (CT), and after necropsy by staining myocardial sections with triphenyl tetrazolium chloride (TTC). Electrocardiography and estimation of serum creatine kinase (CK) activity were also performed. In the 25 animals that survived 24 h, the results of all tests showed that there was less myocardial damage in the animals treated with the two lymphagogues than in those treated with placebo, and less damage with CLS 2210 than with hyaluronidase. The good correlation between the volume of ischemic tissue as assessed by CT in vivo and as assessed by TTC staining after necropsy (r = 0.959) confirms that the CT perfusion phase defect accurately reflects the volume of tissue at risk during the evolution of MI. This study has shown that CLS 2210 is at least as effective as hyaluronidase in reducing myocardial damage due to coronary artery occlusion in dogs.

Animals↗