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-ARI8, CAS 124066-40-6), on the diabetic complications of streptozotocin-induced diabetic rats were studied. The daily administration of BAL-ARI8 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-ARI8 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-ARI8 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 (greater than 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.
Gervasi
G B
GB
Baldacci Research Laboratories, Pisa, Italy.
Bartoli
C
C
Catalani
R
R
Farina
C
C
Carpita
G
G
Caccia
G
G
Ammannati
P
P
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002386:Cataract / Q000209:etiology / Q000517:prevention & control; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D004591:Electrophoresis, Polyacrylamide Gel; D007908:Lens, Crystalline / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008970:Molecular Weight; D011506:Proteins / Q000378:metabolism; D011507:Proteinuria / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013012:Sorbitol / Q000097:blood / Q000378:metabolism; D014966:Xanthenes / Q000494:pharmacology*; D044004:Xanthones
D001786:Blood Glucose; D011506:Proteins; D014966:Xanthenes; D044004:Xanthones; C074179:BAL-ARI8; D013012:Sorbitol; D000449:Aldehyde Reductase