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

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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Journal of Pharmacology Elsevier

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

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Publisher
Elsevier
Copyright
Copyright © 2001 Elsevier Science B.V.
ISSN
0014-2999
D.O.I.
10.1016/S0014-2999(01)01196-7
Publisher site
See Article on Publisher Site

Abstract

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.

Journal

European Journal of PharmacologyElsevier

Published: Oct 5, 2001

References

  • Myocardial cation contents during induction of calcium paradox
    Alto, L.E.; Dhalla, N.S.
  • In vitro antioxidant properties of calcium dobesilate
    Brunet, J.; Farine, J.C.; Garay, R.P.; Hannaert, P.
  • Antioxidant treatment of experimental diabetic retinopathy in rats with nicanartine
    Hammes, H.P.; Bartmann, A.; Engel, L.; Wulfroth, P.
  • Oxidative stress measurement by in vivo electron spin resonance spectroscopy in rats with streptozotocin-induced diabetes
    Sano, T.; Umeda, F.; Hashimoto, T.; Nawata, H.; Utsumi, H.
  • Ocular blood flow and associated functional deviations in diabetic retinopathy
    Schmetterer, L.; Woltz, M.
  • Reperfusion of occluded capillary beds in diabetic retinopathy
    Takahashi, K.; Kishi, S.; Muraoka, K.; Shimizu, K.
  • Automated spectrophotometric method for determining oxidized and reduced glutathione in liver
    Teare, J.P.; Punchard, N.A.; Powell, J.J.; Lumb, P.J.; Mitchell, W.D.; Thompson, R.P.H.

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