title: Renal antifibrotic effect of N-acetyl-seryl-aspartyl-lysyl-proline in diabetic rats.
abstract: OBJECTIVE
  Diabetic nephropathy is the main cause of end-stage renal disease. N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP), a physiological tetrapeptide hydrolyzed by the angiotensin-converting enzyme (ACE), has antifibrotic effects in the cardiovascular system and in the kidney in experimental models of hypertension, heart failure and renal disease. The aim of the study was to evaluate the effect of Ac-SDKP in diabetic nephropathy and the potential additive effect of Ac-SDKP, when compared to ACE inhibitors alone, on the development of renal fibrosis.
  
  
  METHODS
  Diabetes was induced in 28 Sprague-Dawley rats by a single intraperitoneal injection of streptozotocin. Control rats (n = 10) received only buffer solution. An ACE inhibitor (ramipril, 3 mg/kg/day) was administered to 11 diabetic rats. After 2 months, Ac-SDKP (1 mg/kg/day) was administered by osmotic minipumps for 8 weeks to 7 diabetic rats and to 6 diabetic rats treated with ramipril. Osmotic minipumps delivered saline solution in the corresponding sham-treated rats (diabetic rats, n = 10, and ramipril-treated diabetic rats, n = 5).
  
  
  RESULTS
  Diabetic rats showed a significant increase in blood glucose level, urinary albumin excretion and renal fibrosis, and a reduction of glomerular nephrin expression with respect to control rats. Ac-SDKP administration significantly reduced renal fibrosis in diabetic rats, without significantly reducing urinary albumin excretion. Ramipril treatment caused a significant decrease in albuminuria and renal fibrosis and restored glomerular nephrin expression. Administration of Ac-SDKP, in addition to ramipril, further reduced renal fibrosis with respect to ramipril alone, while it did not improve the antiproteinuric effect of ramipril.
  
  
  CONCLUSIONS
  Ac-SDKP administration reduces renal fibrosis in diabetic nephropathy. Addition of Ac-SDKP to ACE inhibition therapy improves the reduction of renal fibrosis with respect to ACE inhibition alone, suggesting a beneficial effect of this pharmacological association in diabetic nephropathy.
authors: Clinica Nefrologica, Az. Ospedaliera San Gerardo, Dipartimento di Scienze della Salute, Università degli Studi di Milano-Bicocca, Monza, Italy. giovanna.castoldi@unimib.it
authors: G
authors: G
authors: Castoldi
authors: C R T
authors: CR
authors: di Gioia
authors: C
authors: C
authors: Bombardi
authors: C
authors: C
authors: Preziuso
authors: M
authors: M
authors: Leopizzi
authors: S
authors: S
authors: Maestroni
authors: B
authors: B
authors: Corradi
authors: G
authors: G
authors: Zerbini
authors: A
authors: A
authors: Stella
mesh_terms: D000419:Albuminuria / Q000188:drug therapy; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D003928:Diabetic Nephropathies / Q000150:complications / Q000188:drug therapy*; D004353:Drug Evaluation, Preclinical; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006131:Growth Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D009400:Nephrosclerosis / Q000209:etiology / Q000517:prevention & control*; D009842:Oligopeptides / Q000494:pharmacology / Q000627:therapeutic use*; D017257:Ramipril / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D006131:Growth Inhibitors; D008565:Membrane Proteins; D009842:Oligopeptides; C113267:nephrin; C058504:goralatide; D017257:Ramipril