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

Calcium dobesilate possesses antioxidant properties and protects against ca pillary permeability by reactive oxygen species in the rat peritoneal cavit y, but whether a similar action can take place in the diabetic rat retina i s unknown. We investigated the oral treatment of diabetic rats with calcium dobesilate on the prevention of free radical-mediated retinal injury induc ed by ischemia/reperfusion (90 min ischemia followed by 3 min and/or 24 h o f reperfusion). Streptozotocin-induced diabetic rats were orally treated wi th 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 signific antly reduce the maldistribution of ion content in diabetic ischemic/reperf used 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 (i i) 59.6% increase in retinal Ca2+ content compared to 107.1% in vehicle-tre ated animals (P < 0.05). In the second series of studies, calcium dobesilat e was found to significantly protect diabetic rat retina against inhibition of Na+/K+-ATPase and Ca2+/Mg2+-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 oxi dized 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), indu ced by ischemia/reperfusion in diabetic rat retina. Finally, 100 mg/kg calc ium dobesilate significantly reduced retinal edema (measured by the thickne ss of the inner plexiform. layer) in diabetic rats. In conclusion, oral tre atment with calcium dobesilate significantly protected diabetic rat retina against oxidative stress induced by ischemia/reperfusion. Whether the antio xidant properties of calcium dobesilate explain, at least in part, its bene ficial therapeutic effects in diabetic retinopathy deserves further investi gation. (C) 2001 Elsevier Science B.V. All rights reserved.