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Treatment with a glycosaminoglycan formulation ameliorates experimental diabetic nephropathy.

Abstract
Previous studies have indicated that administration of glycosaminoglycans can prevent some of the morphological and physiological alterations which occur in experimental diabetic nephropathy. The aims of this study were to further elucidate the effect of these drugs on glomerular basement membrane permeability by dextran clearance studies, to test the ability of glycosaminoglycans to revert established diabetic nephropathy and to examine the effect of glycosaminoglycans on renal extracellular matrix synthesis. Five groups of Sprague-Dawley rats were studied for 12 months: two control groups (treated or untreated non-diabetic), three streptozotocin diabetic animal groups, two of which received a glycosaminoglycan formulation, one from the induction of diabetes and the other after the fifth month of diabetes. At five months the 35S-sulfate glomerular incorporation, albuminuria, glomerular basement membrane thickness and anionic charge density were determined. At 12 months albuminuria, renal collagen IV and perlecan mRNA levels, anionic and neutral dextran clearances, glomerular basement membrane morphometry, and mesangial cell proliferation were evaluated. We demonstrate that long-term administration of glycosaminoglycans prevents renal morphological and functional alterations in diabetic rats and appears to revert established diabetic renal lesions. Glycosaminoglycan administration modified renal matrix composition by the normalization of collagen gene expression and increasing glomerular 35S-sulfate incorporation.
AuthorsG Gambaro, A P Venturini, D M Noonan, W Fries, G Re, S Garbisa, C Milanesi, A Pesarini, A Borsatti, E Marchi
JournalKidney international (Kidney Int) Vol. 46 Issue 3 Pg. 797-806 (Sep 1994) ISSN: 0085-2538 [Print] United States
PMID7527876 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Dextrans
  • Glycosaminoglycans
  • Heparan Sulfate Proteoglycans
  • Heparin, Low-Molecular-Weight
  • Proteoglycans
  • RNA, Messenger
  • perlecan
  • Collagen
  • Heparitin Sulfate
Topics
  • Animals
  • Cell Membrane Permeability (drug effects)
  • Collagen (biosynthesis, genetics)
  • Dextrans (metabolism)
  • Diabetes Mellitus, Experimental (drug therapy, metabolism, pathology)
  • Diabetic Nephropathies (drug therapy, metabolism, pathology)
  • Glomerular Filtration Rate
  • Glycosaminoglycans (therapeutic use)
  • Heparan Sulfate Proteoglycans
  • Heparin, Low-Molecular-Weight (therapeutic use)
  • Heparitin Sulfate (biosynthesis, genetics)
  • Kidney Glomerulus (metabolism, pathology)
  • Male
  • Proteoglycans (biosynthesis, genetics)
  • RNA, Messenger (analysis)
  • Rats
  • Rats, Sprague-Dawley

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