LR-90 a new advanced glycation endproduct inhibitor prevents progression of diabetic nephropathy in streptozotocin-diabetic rats

摘要: Advanced glycation and lipoxidation endproducts have been implicated in the pathogenesis of diabetic complications, including nephropathy. LR-90, a new advanced endproduct inhibitor, was investigated for its effects on development renal disease rats. Diabetic animals were randomly allocated into groups receiving LR-90 or vehicle (untreated). Age- weight-matched non-diabetic rats studied concurrently. Body weight, plasma glucose, glycated haemoglobin, urinary albumin creatine excretions measured serially. Kidney histopathology, AGE accumulation cells tissues, protein oxidation, also examined. In vitro assays used to assess possible mechanism action LR-90. inhibited increase creatinine concentrations, concentrations circulating without any effect glycaemic control. treated-rats showed higher body weights than untreated prevented glomerulosclerosis, tubular degeneration collagen deposition kidney. AGE-induced cross-linking fluorescence tail reduced by treatment. decreased kidney glomeruli nitrotyrosine cortex. vitro, capable reacting with reactive carbonyl compounds more potent metal chelator pyridoxamine aminoguanidine. reduces vivo accumulation, AGE-protein could be beneficial preventing progression The inhibitory therapeutic attributed, at least part, ability react species and/or chelating activity that inhibits glycoxidative-AGE formation.