Intervention with the aldose reductase inhibitor, tolrestat, in renal and retinal lesions of streptozotocin-diabetic rats

Intervention with the aldose reductase inhibitor, tolrestat, in renal and retinal lesions of... 125 34 34 10 10 M. L. McCaleb M. L. McKean T. C. Hohman N. Laver W. G. Robison Jr. Wyeth-Ayerst Research Princeton New Jersey USA The National Eye Institute National Institute of Health Bethesda Maryland USA Summary The progressive increase in urinary albumin excretion, which precedes the development of diabetic nephropathy, can be prevented in diabetic rats if the aldose reductase inhibitor, tolrestat, is administered at the initiation and throughout the duration of hyperglycaemia. We therefore determined the ability of tolrestat to intervene in the further progression of already established urinary albumin excretion of streptozotocin-diabetic female Wistar rats. Two months after streptozotocin injection, diabetic rats were grouped as low-urinary albumin excretion (0.2–1.0 mg albumin/day) or high-urinary albumin excretion (1.9–5.9 mg albumin/day), at which time tolrestat intervention (25 mg/kg per day) was begun for half of the diabetic rats in each urinary albumin excretion group. After six months of treatment tolrestat caused a significant reduction in the urinary albumin excretion rate of the low-urinary albumin excretion group only. The diabetes-induced rise of total urinary protein in both groups was significantly reduced by tolrestat. Furthermore, the diabetes-induced increase (49%) in the thickness of the basement membranes of retinal capillaries from the outer plexiform layer was significantly diminished by tolrestat administration. In conclusion, intervention therapy with the aldose reductase inhibitor, tolrestat, can reduce the progression of urinary albumin excretion and retinal basement membrane thickening in long-term diabetic rats. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Diabetologia Springer Journals

Intervention with the aldose reductase inhibitor, tolrestat, in renal and retinal lesions of streptozotocin-diabetic rats

Diabetologia, Volume 34 (10) – Oct 1, 1991

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Publisher
Springer Journals
Copyright
Copyright © 1991 by Springer-Verlag
Subject
Medicine & Public Health; Human Physiology; Internal Medicine; Metabolic Diseases
ISSN
0012-186X
eISSN
1432-0428
DOI
10.1007/BF00401513
Publisher site
See Article on Publisher Site

Abstract

125 34 34 10 10 M. L. McCaleb M. L. McKean T. C. Hohman N. Laver W. G. Robison Jr. Wyeth-Ayerst Research Princeton New Jersey USA The National Eye Institute National Institute of Health Bethesda Maryland USA Summary The progressive increase in urinary albumin excretion, which precedes the development of diabetic nephropathy, can be prevented in diabetic rats if the aldose reductase inhibitor, tolrestat, is administered at the initiation and throughout the duration of hyperglycaemia. We therefore determined the ability of tolrestat to intervene in the further progression of already established urinary albumin excretion of streptozotocin-diabetic female Wistar rats. Two months after streptozotocin injection, diabetic rats were grouped as low-urinary albumin excretion (0.2–1.0 mg albumin/day) or high-urinary albumin excretion (1.9–5.9 mg albumin/day), at which time tolrestat intervention (25 mg/kg per day) was begun for half of the diabetic rats in each urinary albumin excretion group. After six months of treatment tolrestat caused a significant reduction in the urinary albumin excretion rate of the low-urinary albumin excretion group only. The diabetes-induced rise of total urinary protein in both groups was significantly reduced by tolrestat. Furthermore, the diabetes-induced increase (49%) in the thickness of the basement membranes of retinal capillaries from the outer plexiform layer was significantly diminished by tolrestat administration. In conclusion, intervention therapy with the aldose reductase inhibitor, tolrestat, can reduce the progression of urinary albumin excretion and retinal basement membrane thickening in long-term diabetic rats.

Journal

DiabetologiaSpringer Journals

Published: Oct 1, 1991

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