Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/13118
Title: The relative roles of advanced glycation, oxidation and aldose reductase inhibition in the development of experimental diabetic nephropathy in the Sprague-Dawley rat.
Authors: Soulis-Liparota, T;Cooper, Mark E;Dunlop, M;Jerums, George
Affiliation: Department of Medicine, University of Melbourne, Austin Hospital, Victoria, Australia.
Issue Date: 1-Apr-1995
Citation: Diabetologia; 38(4): 387-94
Abstract: Advanced glycation is an important pathogenic mechanism in the development of diabetic complications. However, other biochemical processes, such as the polyol pathway or lipid and protein oxidation which can interact with advanced glycation can also yield tissue fluorescence and may also be implicated in the genesis of diabetic microangiopathy. Aminoguanidine is an inhibitor of advanced glycation, but it is not known if all of its effects are mediated by this mechanism. The present study explores the relative contributions of aldose reductase, oxidative stress and advanced glycation on the development of aortic and renal fluorescence and urinary albumin excretion in streptozotocin diabetic rats. The study groups included non-diabetic (control), streptozotocin diabetic rats and diabetic rats receiving aminoguanidine, the anti-oxidants butylated hydroxytoluene and probucol and the aldose reductase inhibitor, ponalrestat. Serial measurements of glycaemic control and urinary albumin excretion were performed every 8 weeks. At 32 weeks, animals were killed, tissues removed and collagen extracted for measurement of fluorescence. Diabetic rats had increased fluorescence in aorta, glomeruli and renal tubules. Aminoguanidine prevented an increase in fluorescence at all three sites suggesting that diabetes-related tissue fluorescence is predominantly due to advanced glycation. Ponalrestat retarded fluorescence in aorta only and butylated hydroxytoluene attenuated fluorescence at the renal sites but not in the aorta. Diabetic rats had increased renal cortical sorbitol levels. Ponalrestat normalized renal cortical sorbitol levels but aminoguanidine did not affect this parameter. The only agent to decrease plasma thiobarbituric acid reactive substances was butylated hydroxytoluene. Diabetic rats developed albuminuria over the 32-week period.(ABSTRACT TRUNCATED AT 250 WORDS)
Internal ID Number: 7796978
URI: http://ahro.austin.org.au/austinjspui/handle/1/13118
URL: http://www.ncbi.nlm.nih.gov/pubmed/7796978
Type: Journal Article
Subjects: Albuminuria
Aldehyde Reductase.antagonists & inhibitors
Animals
Antioxidants.pharmacology
Blood Glucose.drug effects.metabolism
Body Weight.drug effects
Butylated Hydroxytoluene.pharmacology
Diabetes Mellitus, Experimental.drug therapy.physiopathology
Diabetic Nephropathies.metabolism.physiopathology.prevention & control
Glycosylation
Guanidines.pharmacology
Hemoglobin A, Glycosylated.metabolism
Kidney Cortex.drug effects.metabolism
Male
Malondialdehyde.blood
Oxidation-Reduction
Phthalazines.pharmacology
Probucol.pharmacology
Rats
Rats, Sprague-Dawley
Sorbitol.metabolism
Appears in Collections:Journal articles

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