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.
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.
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