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Title: Renoprotective effects of a novel inhibitor of advanced glycation.
Austin Authors: Forbes, J M;Soulis, T;Thallas, Vicki;Panagiotopoulos, Sianna ;Long, D M;Vasan, S;Wagle, D;Jerums, George ;Cooper, Mark E
Affiliation: Department of Medicine, University of Melbourne, Austin and Repatriation Medical Centre, West Heidelberg, Australia
Issue Date: 1-Jan-2001
Publication information: Diabetologia; 44(1): 108-14
Abstract: ALT-946, an inhibitor of advanced glycation with a minimal inhibitory effect on nitric oxide synthase, was compared with aminoguanidine in experimental diabetic nephropathy.In vitro and in vivo assays were used to assess the ability of ALT-946 to inhibit AGE-protein cross-link formation. Diabetic animals were randomly allocated into groups receiving aminoguanidine for 32 weeks, ALT-946 or vehicle (untreated). As a delayed intervention protocol, an additional diabetic group was treated with ALT-946 from week 16 to week 32 of the study. Non-diabetic rats were studied concurrently. Systolic blood pressure, body weight, plasma glucose, glycated haemoglobin and urinary albumin excretion were measured serially. Accumulation of advanced-glycation end products in the kidney was assessed by immunohistochemistry.The ALT-946 inhibitor was more potent than aminoguanidine in inhibiting AGE-protein cross-linking both in vitro and in vivo. Increased albuminuria observed in diabetic rats was attenuated in all three treatment groups. We found no difference in body weight, blood pressure or glycaemic control with any of the treatments. The untreated diabetic group had a twofold increase in glomerular staining for advanced-glycation end products compared with the diabetic groups which received treatment.ALT-946 is a potent inhibitor of advanced renal glycation end-product accumulation and reproduces the renoprotective effects of aminoguanidine. Therefore, ALT-946 should be considered as a treatment for preventing or retarding diabetic nephropathy.
Gov't Doc #: 11206401
DOI: 10.1007/s001250051587
ORCID: 0000-0002-0845-0001
Type: Journal Article
Subjects: Animals
Cross-Linking Reagents
Diabetes Mellitus, Experimental.complications.metabolism
Diabetic Nephropathies.prevention & control
Enzyme Inhibitors
Glomerular Filtration Rate
Glycosylation End Products, Advanced.analysis.antagonists & inhibitors
Guanidines.therapeutic use
Kidney Glomerulus.chemistry
Nitric Oxide Synthase.antagonists & inhibitors
Rats, Sprague-Dawley
Serum Albumin, Bovine
Appears in Collections:Journal articles

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