Gliclazide attenuates the intracellular Ca2+ changes induced in vitro by ischemia in the retinal slices of rats with streptozotocin-induced diabetes.
OBJECTIVE
To investigate the dynamics of the intracellular Ca2+ concentration ([Ca2+]i) during retinal ischemia in rats with streptozotocin (STZ)-induced diabetes and the effect of gliclazide, a sulfonylurea with a potent free-radical scavenging activity on ischemia-induced [Ca2+]i dynamics.


METHODS
Rats with STZ (65 mg/kg) induced diabetes were divided into three groups: the untreated diabetic group, the gliclazide-treated group, and the glibenclamide-treated group. An ischemic condition was imposed in vitro on the retinal slices by perfusion with an oxygen/glucose deprived solution. The [Ca2+]i was measured in individual layers of the rat retinal slices loaded with the Ca2+ indicator fluo-3.


RESULTS
As compared to that in the normal rat retina, both the amplitude and the kinetics of the [Ca2+]i increase were suppressed in the intermediate layers of the retinal slices from the diabetic rats under the ischemic condition. These changes were attenuated by the administration of gliclazide but not by that of glibenclamide.


CONCLUSIONS
Hyperglycemia influences ischemia-induced [Ca2+]i dynamics predominantly in the intermediate layers of the retina, and gliclazide, as compared to glibenclamide without a free radical scavenging activity, potently attenuates the ischemia-induced changes in the calcium dynamics.
Kinukawa
Jiro
J
Department of Ophthalmology and Medical Science, Tohoku University Graduate School of Medicine, Sendai Miyagi, Japan.
Shimura
Masahiko
M
Harata
Nobutoshi
N
Tamai
Makoto
M
D000814:Aniline Compounds / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003930:Diabetic Retinopathy / Q000378:metabolism*; D005907:Gliclazide / Q000494:pharmacology*; D005905:Glyburide / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores; D007511:Ischemia / Q000378:metabolism*; D018613:Microscopy, Confocal; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000187:drug effects* / Q000378:metabolism; D013311:Streptozocin; D014966:Xanthenes / Q000378:metabolism
D000814:Aniline Compounds; D007004:Hypoglycemic Agents; D007476:Ionophores; D014966:Xanthenes; C059715:Fluo-3; D015759:Ionomycin; D013311:Streptozocin; D005907:Gliclazide; D005905:Glyburide; D002118:Calcium