Renal antifibrotic effect of n-acetyl-seryl-aspartyl-lysyl-proline in diabetic rats

G. Castoldi, C. R T Di Gioia, C. Bombardi, C. Preziuso, M. Leopizzi, S. Maestroni, B. Corradi, G. Zerbini, A. Stella

Research output: Contribution to journalArticle

Abstract

Background and Aim: 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. Method: 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. Conclusion: 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.

Original languageEnglish
Pages (from-to)65-73
Number of pages9
JournalAmerican Journal of Nephrology
Volume37
Issue number1
DOIs
Publication statusPublished - 2013

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Ramipril
Kidney
Fibrosis
Diabetic Nephropathies
Peptidyl-Dipeptidase A
Angiotensin-Converting Enzyme Inhibitors
Albumins
goralatide
Enzyme Therapy
Albuminuria
Streptozocin
Cardiovascular System
Intraperitoneal Injections
Sodium Chloride
Chronic Kidney Failure
Sprague Dawley Rats
Blood Glucose
Buffers
Theoretical Models
Heart Failure

Keywords

  • Angiotensin-converting enzyme inhibitors
  • Diabetic nephropathy
  • Experimental models
  • Fibrosis
  • N-acetyl-seryl- aspartyl-lysyl-proline
  • Rats

ASJC Scopus subject areas

  • Nephrology

Cite this

Castoldi, G., Di Gioia, C. R. T., Bombardi, C., Preziuso, C., Leopizzi, M., Maestroni, S., ... Stella, A. (2013). Renal antifibrotic effect of n-acetyl-seryl-aspartyl-lysyl-proline in diabetic rats. American Journal of Nephrology, 37(1), 65-73. https://doi.org/10.1159/000346116

Renal antifibrotic effect of n-acetyl-seryl-aspartyl-lysyl-proline in diabetic rats. / Castoldi, G.; Di Gioia, C. R T; Bombardi, C.; Preziuso, C.; Leopizzi, M.; Maestroni, S.; Corradi, B.; Zerbini, G.; Stella, A.

In: American Journal of Nephrology, Vol. 37, No. 1, 2013, p. 65-73.

Research output: Contribution to journalArticle

Castoldi, G, Di Gioia, CRT, Bombardi, C, Preziuso, C, Leopizzi, M, Maestroni, S, Corradi, B, Zerbini, G & Stella, A 2013, 'Renal antifibrotic effect of n-acetyl-seryl-aspartyl-lysyl-proline in diabetic rats', American Journal of Nephrology, vol. 37, no. 1, pp. 65-73. https://doi.org/10.1159/000346116
Castoldi G, Di Gioia CRT, Bombardi C, Preziuso C, Leopizzi M, Maestroni S et al. Renal antifibrotic effect of n-acetyl-seryl-aspartyl-lysyl-proline in diabetic rats. American Journal of Nephrology. 2013;37(1):65-73. https://doi.org/10.1159/000346116
Castoldi, G. ; Di Gioia, C. R T ; Bombardi, C. ; Preziuso, C. ; Leopizzi, M. ; Maestroni, S. ; Corradi, B. ; Zerbini, G. ; Stella, A. / Renal antifibrotic effect of n-acetyl-seryl-aspartyl-lysyl-proline in diabetic rats. In: American Journal of Nephrology. 2013 ; Vol. 37, No. 1. pp. 65-73.
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AU - Leopizzi, M.

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