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Title: Ramipril and aminoguanidine restore renal lysosomal processing in streptozotocin diabetic rats.
Austin Authors: Osicka, Tanya M;Kiriazis, Z;Pratt, L M;Jerums, George ;Comper, Wayne D
Affiliation: Department of Medicine, University of Melbourne, Austin & Repatriation Medical Centre, Heidelberg, Victoria, Australia
Issue Date: 1-Feb-2001
Publication information: Diabetologia; 44(2): 230-6
Abstract: We aimed to examine the time course for the diabetes-related changes in renal lysosomal processing and to determine whether these changes can be prevented by aminoguanidine or ramipril treatment.The percentage desulphation of intravenously injected tritium labelled dextran sulphate ([3H]DSO4) in the urine, as determined by ion-exchange chromatography, was used as a marker of lysosomal sulphatase activity. Sulphatase activity was determined 1, 2, 3 and 4 weeks after the onset of diabetes in rats as well as in rats treated with either aminoguanidine or ramipril for twelve weeks.The amount of totally desulphated [3H]DSO4 in urine collected from control rats was 65.6 +/- 0.8%. This was significantly reduced in diabetic rats two (57.4 +/- 1.4% desulphated), three (56.8 +/- 1.3 % desulphated) and four (52.9 +/- 2.2% desulphated) weeks after the onset of diabetes. The significant decrease in the amount of totally desulphated [3H]DSO4 in the urine also found at 12 weeks after the onset of diabetes was not affected by drug treatment. There was no significant difference in the amount of partially desulphated [3H]DSO4 in the urine between all the study groups. However, the increase in totally sulphated [3H]DSO4 in the urine collected from diabetic rats (8.7 +/- 1.7 % sulphated) compared with that of control rats (2.2 +/- 0.5% sulphated) was normalised by treatment with both aminoguanidine (4.8 +/- 1.6% sulphated) or ramipril (4.5 +/- 0.8% sulphated).These results raise the possibility that the diabetes-induced changes in renal lysosomal processing may be one of the initial events in the development of diabetic nephropathy. Aminoguanidine and ramipril, known for their different mechanism of action, seem to prevent diabetes-induced changes in lysosomal processing either through their effects on enzyme activity within the lysosome or through their effects on the trafficking of molecules to and from the lysosome.
Gov't Doc #: 11270681
DOI: 10.1007/s001250051604
Type: Journal Article
Subjects: Angiotensin-Converting Enzyme Inhibitors.therapeutic use
Blood Glucose.metabolism
Blood Pressure
Body Weight
Chromatography, Ion Exchange
Dextran Sulfate.urine
Diabetes Mellitus, Experimental.drug therapy.enzymology.physiopathology
Diabetic Nephropathies.prevention & control
Enzyme Inhibitors.therapeutic use
Glomerular Filtration Rate
Guanidines.therapeutic use
Nitric Oxide Synthase.antagonists & inhibitors
Ramipril.therapeutic use
Rats, Sprague-Dawley
Appears in Collections:Journal articles

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