Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Proteinuria was diminished by concomitant oral administration of sorbinil, an aldose reductase inhibitor to streptozotocin-induced diabetic rats. Animals were placed in one of three groups: control, diabetic, sorbinil-treated diabetic. For a period of 10 weeks, 24-hour urine samples were analyzed weekly for volume, glucose, ketone, total protein (Pesce-Strande) and individual protein components having molecular weights between 15,000 and 120,000 daltons. The latter were examined by polyacrylamide gel electrophoresis and quantitated by laser densitometric analysis. Results indicated that controls excreted albumin (68,000 daltons) and low-molecular weight proteins between 15,000 and 20,000 daltons. Throughout the 10-week period of diabetes, there was a 7- to 12-fold increase in total urinary protein excreted in 24 h. Diabetic-induced proteinuria primarily resulted from excretion of newly detected proteins having molecular weights of 30,000-100,000 daltons and an increase amount of albumin. Sorbinil treatment prevented approximately 70% of the increase in total protein excretion despite persistent hyperglycemia, glycosuria and ketonuria. Laser densitometric analysis indicated that the aldose reductase inhibitor decreased by 70% the excretion of newly detected proteins and albumin while maintaining the 15,000- to 20,000-dalton proteins. These results suggest that the polyol pathway is implicated in diabetic-induced proteinuria and inhibition of aldose reductase may represent a therapeutic approach for management of diabetic nephropathy.
 ...
PMID:Diminished proteinuria in diabetes mellitus by sorbinil, an aldose reductase inhibitor. 308 Jul 63

Neuropathy and retinopathy are two potentially serious late complications of diabetes. There is accumulating evidence that the development of these conditions is closely related to increased activity of the polyol pathway, which occurs in certain tissues as a consequence of long term hyperglycaemia. Symptomatic diabetic neuropathy may appear as one of many forms and is frequently accompanied by pain. Diabetic retinopathy is a progressive degeneration of the retina that represents one of the major causes of blindness in the developed world. A good prognosis for either of these conditions is believed to rely on early diagnosis and optimisation of glycaemic control as they become less reversible with progression of cellular damage. A new approach to the treatment of these and other late complications of diabetes may be offered by recently developed drugs, such as sorbinil, that inhibit the enzyme aldose reductase. In various animal models of late complications of diabetes sorbinil and other aldose reductase inhibitors have been shown to reverse some of the biochemical and physiological changes believed to underlie these complications. These include prevention or reversal of the accumulation of sorbitol and depletion of myo-inositol in nerve, lens and renal glomeruli. Sorbinil also counteracts the slowing of nerve conduction velocities, reverses the structural changes of Sipple stages I and II cataracts and prevents proteinuria in diabetic rats. Orally administered sorbinil is absorbed rapidly and reaches steady state plasma concentrations after 6 to 10 days' administration. Its elimination half-life is long (38-52 hours) and much greater than that of another aldose reductase inhibitor, tolrestat (10-12 hours). Within the dose range 50-250 mg about one-third of administered sorbinil appears in the urine as unchanged drug. In the small number of clinical studies of diabetic patients with neuropathies sorbinil has demonstrated limited therapeutic effects. There is now a requirement for studies of its prophylactic use and its therapeutic use in patients with diabetic neuropathy in the early stages of development.
 ...
PMID:Aldose reductase inhibitors and late complications of diabetes. 309 44

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.
 ...
PMID:Reversal of proteinuria by sorbinil, an aldose reductase inhibitor in spontaneously diabetic (BB) rats. 312 36