Effects of a new aldose reductase inhibitor on diabetic complications in rats.

The effects of a new aldose reductase inhibitor, 7-fluoro-2-(N-methyl-N-carboxymethyl)sulfamoyl xanthone (BAL-AR18, CAS 124066-40-6), on the diabetic complications of streptozotocin-induced diabetic rats were studied. The daily administration of BAL-AR18 throughout the 8-week course of the experiment sharply decreased the sorbitol accumulation in the lens of the diabetic rats. The incidence of cataract formation was also reduced, being detected in only 45 % of BAL-AR18 treated animals, against the 100 % of diabetic controls showing cataract after 8 weeks from diabetes onset. On the other hand, the serum glucose levels remained unchanged. In diabetic controls, there was about a 2.5-fold increase of the total protein urinary excretion during the 24 h. Treatment with BAL-AR18 prevented up to 70 % of this increase. Individual protein components were examined by polyacrylamide gel electrophoresis and quantitated by laser densitometric analysis. Diabetic-induced proteinuria primarily resulted from excretion of newly detected proteins with molecular weight in the range 30,000-60,000 D, together with an increase of albumin (25 % of the total excretion) and the presence of new higher molecular weight proteins (> 66,000 D). BAL-ARI8 administration resulted in a shift of the protein profile back toward normality i.e. 73 % of proteins with molecular weight below 30,000 D, 7.5 % albumin and no proteins above 66,000 D. These results suggest that BAL-ARI8 may represent a therapeutic approach for the management of diabetic complications.