Aldose reductase inhibition by ponalrestat (statil) does not prevent proteinuria in long-term diabetic rats.
The aldose reductase pathway has been implicated in the development of chronic complications of diabetes. In this study, we investigated the effect of an aldose reductase inhibitor, statil, on glomerular synthesis of heparan sulfate and albuminuria in male Wistar rats made diabetic with streptozotocin. Heparan sulfate is the predominant glycosaminoglycan (GAG) proteoglycan in the glomerular basement membrane (GBM). It confers a negative charge on the GBM, and its loss has been related to the presence of albumin in the urine. Diabetic rats synthesized less glomerular heparan sulfate and excreted more albumin than normal rats. Glomerular sorbitol concentration was significantly higher in diabetic than in normal rats. Chronic treatment of diabetic rats with statil did not improve either heparan sulfate synthesis or albuminuria despite normalization of glomerular sorbitol content. The present study does not support the role of excess sorbitol in the development of glomerular abnormalities in this rat model of streptozotocin diabetes.
Reddi
A S
AS
Department of Medicine, UMDN New Jersey Medical School, Newark 07103.
Jyothirmayi
G N
GN
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D001485:Basement Membrane / Q000187:drug effects / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D002809:Chondroitin Sulfates / Q000096:biosynthesis; D003404:Creatinine / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology* / Q000652:urine; D004044:Dietary Proteins; D004591:Electrophoresis, Polyacrylamide Gel; D006497:Heparan Sulfate / Q000096:biosynthesis; D007668:Kidney / Q000187:drug effects; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010793:Phthalazines / Q000494:pharmacology*; D011188:Potassium / Q000097:blood; D011507:Proteinuria / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar; D013012:Sorbitol / Q000378:metabolism; D013997:Time Factors
D000449:Aldehyde Reductase; D001786:Blood Glucose; D002809:Chondroitin Sulfates; D003404:Creatinine; D004044:Dietary Proteins; D006497:Heparan Sulfate; D010793:Phthalazines; D011188:Potassium; D013012:Sorbitol; C042829:ponalrestat