Reversal of proteinuria by sorbinil, an aldose reductase inhibitor in spontaneously diabetic (BB) rats.
Sorbinil, an aldose reductase inhibitor, was examined as a therapeutic agent to arrest and/or reverse proteinuria in 'type 1' insulin-dependent BB rats having spontaneous diabetes mellitus. Prior to sorbinil treatment, diabetic rats exhibited hyperglycemia and increased urinary excretion of urobilinogen, glucose and protein. To assess proteinuria, 24-hour urine samples were analyzed for both total protein and individual components between 30,000 and 100,000 daltons. Daily oral administration of sorbinil (20 mg/kg body weight) was initiated and the aforementioned parameters reevaluated after 1, 2 and 4 months. Results indicated that after 1 month of sorbinil treatment, urobilinogen was normalized in all diabetic BB rats (n = 12), whereas urinary protein excretion was either diminished (67%) or remained constant (16%), despite persistence of hyperglycemia and glycosuria. These therapeutic effects were sustained after 2 months of sorbinil treatment. After 4 months, protein excretion was normalized (6.56 +/- 3.34 mg/24 h), despite persistence of hyperglycemia and glycosuria (n = 12); in marked contrast, 6 untreated rats continued to exhibit proteinuria (17.76 +/- 2.59 mg/day). Sorbinil diminished albumin and a series of urinary proteins between 30,000 and 100,000 daltons, suggesting that sorbinil may represent a therapeutic approach to manage diabetic nephropathy as indicated by diminution of proteinuria.
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000652:urine*; D007093:Imidazoles / Q000627:therapeutic use*; D048289:Imidazolidines; D007328:Insulin / Q000097:blood; D008297:Male; D008970:Molecular Weight; D011507:Proteinuria / Q000188:drug therapy*; D051381:Rats; D011919:Rats, Inbred Strains; D013401:Sugar Alcohol Dehydrogenases / Q000037:antagonists & inhibitors*
D001786:Blood Glucose; D007093:Imidazoles; D048289:Imidazolidines; D007328:Insulin; D013401:Sugar Alcohol Dehydrogenases; D000449:Aldehyde Reductase; C026411:sorbinil