N-Acetyl-seryl-aspartyl-lysyl-proline Alleviates Renal Fibrosis Induced by Unilateral Ureteric Obstruction in BALB/C Mice

• Published in: Mediators of Inflammation Vol. 2015; no. 2015; pp. 99 - 108-109
• Main Authors: Tang, Sydney C. W., Huang, Xiao Ru, Lin, Miao, Wong, Dickson W. L., Wu, Hao Jia, Yiu, Wai Han, Chan, Gary C. W., Lan, Hui Y.
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Limiteds 01.01.2015; Hindawi Publishing Corporation; John Wiley & Sons, Inc; Hindawi Limited
• Subjects: Actins - metabolism; Angiotensin converting enzyme; Angiotensin-Converting Enzyme Inhibitors - therapeutic use; Animals; Captopril - chemistry; Chemokine CCL2 - metabolism; Chronic kidney failure; Collagen Type IV - metabolism; Enzymes; Fibrosis; Fibrosis - drug therapy; Gene expression; Histology; Immunohistochemistry; Inflammation; Kidney Diseases - drug therapy; Kidneys; Laboratory animals; Lymphocytes - cytology; Macrophages - cytology; Macrophages - metabolism; Male; Mice; Mice, Inbred BALB C; Morphology; Muscle, Smooth - metabolism; Nephrology; Oligopeptides - therapeutic use; Physiological aspects; Real-Time Polymerase Chain Reaction; Rodents; Studies; Ureteral Obstruction - drug therapy
• ISSN: 0962-9351; 1466-1861
• DOI: 10.1155/2015/283123

To expand the armamentarium of treatment for chronic kidney disease (CKD), we explored the utility of boosting endogenously synthesized N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP), which is augmented by inhibition of the angiotensin converting enzyme. Male BALB/c mice underwent unilateral ureteral ligation (UUO) or sham operation and received exogenously administered Ac-SDKP delivered via a subcutaneous osmotic minipump or Captopril treatment by oral gavage. Seven days after UUO, there were significant reductions in the expression of both collagen 1 and collagen 3 in kidneys treated with Ac-SDKP or Captopril, and there was a trend towards reductions in collagen IV, α-SMA, and MCP-1 versus control. However, no significant attenuation of interstitial injury or macrophage infiltration was observed. These findings are in contrary to observations in other models and underscore the fact that a longer treatment time frame may be required to yield anti-inflammatory effects in BALB/c mice treated with Ac-SDKP compared to untreated mice. Finding an effective treatment regimen for CKD requires fine-tuning of pharmacologic protocols.