(5-(3-thienyl)tetrazol-1-yl)acetic-acid and Diabetic-Angiopathies

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.

Topics: 2,3-Diphosphoglycerate; Aldehyde Reductase; Animals; Blood Glucose; Carbohydrate Metabolism; Diabetes Mellitus, Experimental; Diabetic Angiopathies; Diabetic Retinopathy; Diphosphoglyceric Acids; Electroretinography; Enzyme Inhibitors; Insulin; Lipids; Male; Platelet Aggregation; Rats; Rats, Wistar; Retina; Tetrazoles; Thiophenes