Effect of an aldose reductase inhibitor on abnormalities of electroretinogram and vascular factors in diabetic rats.
The effect of an aldose reductase inhibitor, [5-(3-thienyl) tetrazol-1-yl] acetic acid (TAT), on the electroretinogram was determined in rats with streptozotocin-induced diabetes. Laboratory chow containing 0.05% TAT was given to rats for 2 months, while other diabetic rats were untreated. Groups of TAT-treated and untreated normal rats were also studied. Treatment with TAT produced significant improvement of the electroretinogram. TAT shortened the peak latencies of the b-wave oscillatory potentials, which were significantly prolonged in untreated diabetic rats (P < 0.0001 vs. untreated normal rats). This was accompanied by a significant decrease in the retinal sorbitol and fructose concentrations (by 46.5% and 25.7%, respectively). TAT treatment of diabetic rats also markedly reduced ADP-induced platelet aggregation and significantly increased the red blood cell 2,3-diphosphoglycerate level, accompanied by a marked reduction in sorbitol and fructose concentrations of platelet and red blood cells. There were significant correlations between the summed b-wave peak latencies and platelet aggregation or the 2,3-diphosphoglycerate level in diabetic rats. These findings suggest that an aldose reductase inhibitor, TAT, has therapeutic value for diabetic retinopathy.
Hotta
N
N
The Third Department of Internal Medicine, Nagoya University School of Medicine, Showa-ku, Japan.
Koh
N
N
Sakakibara
F
F
Nakamura
J
J
Hara
T
T
Hamada
Y
Y
Fukasawa
H
H
Kakuta
H
H
Sakamoto
N
N
D019794:2,3-Diphosphoglycerate; D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D050260:Carbohydrate Metabolism; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology; D003925:Diabetic Angiopathies / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D003930:Diabetic Retinopathy / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D004163:Diphosphoglyceric Acids / Q000097:blood; D004596:Electroretinography / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012160:Retina / Q000187:drug effects / Q000378:metabolism; D013777:Tetrazoles / Q000494:pharmacology*; D013876:Thiophenes / Q000494:pharmacology*
D001786:Blood Glucose; D004163:Diphosphoglyceric Acids; D004791:Enzyme Inhibitors; D007328:Insulin; D008055:Lipids; D013777:Tetrazoles; D013876:Thiophenes; C080974:(5-(3-thienyl)tetrazol-1-yl)acetic acid; D019794:2,3-Diphosphoglycerate; D000449:Aldehyde Reductase