title: Effects of inhibition of glycation and oxidative stress on the development of diabetic nephropathy in rats.
abstract: We investigated whether aminoguanidine (AG), an inhibitor of advanced glycated end product formation, or probucol (PB), a free radical scavenger, could influence signs of glomerular and distal tubular function and morphological changes in kidneys of male Wistar rats after 6 months of streptozocin (STZ)-induced diabetes. Diabetic rats had a higher kidney weight/body weight ratio (P<.001), but neither AG nor PB influenced the increased ratio. Diabetes caused an increased urinary albumin excretion (P<.05), which was normalized by AG, but further exaggerated by PB (P<.001). Diabetes also caused an increase in the urinary excretion of Tamm-Horsfall protein (P<.001). Both AG and PB attenuated this increase (P<.05 for both). A few glomeruli displayed focal thickening of varying degrees. Silver staining disclosed the glomerulopathy to be intercapillary glomerulosclerosis. Rats on PB-enriched diet displayed less pronounced changes than untreated rats (P<.01), while AG had no effect. The results suggest that oxidative stress could be involved in the development of diabetic nephropathy.
authors.affiliation: Wallenberg Research Laboratory, University Hospital MAS, Malmö, Sweden. carl-david.agardh@endo.mas.lu.se
authors.forename: Carl David
authors.initials: CD
authors.lastname: Agardh
authors.forename: Unne
authors.initials: U
authors.lastname: Stenram
authors.forename: Ole
authors.initials: O
authors.lastname: Torffvit
authors.forename: Elisabet
authors.initials: E
authors.lastname: Agardh
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000503:physiopathology*; D018450:Disease Progression; D016166:Free Radical Scavengers / Q000494:pharmacology*; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors; D006031:Glycosylation; D006146:Guanidines / Q000494:pharmacology*; D007678:Kidney Glomerulus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D007686:Kidney Tubules, Distal / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D018384:Oxidative Stress / Q000502:physiology*; D011341:Probucol / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D016166:Free Radical Scavengers; D017127:Glycation End Products, Advanced; D006146:Guanidines; D011341:Probucol; C004479:pimagedine