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Effects of inhibition of glycation and oxidative stress on the development of diabetic nephropathy in rats.

Agardh, Carl David; Stenram, Unne LU ; Torffvit, Ole LU and Agardh, Elisabet LU (2002) In Journal of Diabetes and its Complications 16(6). p.395-400
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... (More)
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. (Less)
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@article{bb1bd286-a922-4d53-ac69-57e9c4bf82d2,
  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&lt;.001), but neither AG nor PB influenced the increased ratio. Diabetes caused an increased urinary albumin excretion (P&lt;.05), which was normalized by AG, but further exaggerated by PB (P&lt;.001). Diabetes also caused an increase in the urinary excretion of Tamm–Horsfall protein (P&lt;.001). Both AG and PB attenuated this increase (P&lt;.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&lt;.01), while AG had no effect. The results suggest that oxidative stress could be involved in the development of diabetic nephropathy.},
  author       = {Agardh, Carl David and Stenram, Unne and Torffvit, Ole and Agardh, Elisabet},
  issn         = {1873-460X},
  keyword      = {Free Radical Scavengers: pharmacology,Diabetic Nephropathies: physiopathology,Disease Progression,Experimental: physiopathology,Probucol: pharmacology,Rats,Animal,Diabetes Mellitus,Non-U.S. Gov't,Distal: physiopathology,Male,Oxidative Stress: physiology,Support,Wistar,Kidney Tubules,Distal: pathology,Distal: drug effects,Kidney Glomerulus: physiopathology,Kidney Glomerulus: pathology,Kidney Glomerulus: drug effects,Guanidines: pharmacology,Advanced: antagonists & inhibitors,Glycosylation End Products,Glycosylation},
  language     = {eng},
  number       = {6},
  pages        = {395--400},
  publisher    = {Elsevier},
  series       = {Journal of Diabetes and its Complications},
  title        = {Effects of inhibition of glycation and oxidative stress on the development of diabetic nephropathy in rats.},
  url          = {http://dx.doi.org/10.1016/S1056-8727(02)00164-2},
  volume       = {16},
  year         = {2002},
}