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NDT Advance Access originally published online on July 25, 2009
Nephrology Dialysis Transplantation 2009 24(9):2701-2708; doi:10.1093/ndt/gfp369
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© The Author [2009]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org



Amelioration of renal ischaemia-reperfusion injury by synthetic oligopeptides related to human chorionic gonadotropin

Nisar A. Khan1,*, Denis Susa2,*, Jan Willem van den Berg1,2, Martin Huisman2, Miriam H. Ameling1, Sandra van den Engel2, Henk P. Roest2, Jan N. M. IJzermans2, Willem A. Dik1, Robbert Benner1,* and Ron W. F. de Bruin2,*

1 Department of Immunology 2 Department of Surgery, Erasmus MC University Medical Center, Rotterdam, The Netherlands

Correspondence and offprint requests to: Ron W. F. de Bruin; E-mail: r.w.f.debruin{at}erasmusmc.nl



  Abstract

Background. We have previously reported that small synthetic oligopeptides related to human β-chorionic gonadotropin (β-hCG) can reduce inflammation. Here we investigated whether such oligopeptides can reduce renal ischaemia-reperfusion injury in the mouse.

Methods. Ten different oligopeptides were administered 1 min before induction of renal ischaemia and 1 min before reperfusion.

Results. Survival at 72 h post-reperfusion was significantly higher in mice treated with oligopeptides MTRV, LQG, VLPALPQ or AQGV as compared to placebo-treated mice. Some oligopeptides were more effective than others. AQGV completely prevented mortality and best preserved kidney function. Next, AQGV was tested in a dose-escalating study in a range of 0.3–30 mg/kg. A survival gain was observed with all doses. Improvement of kidney function was observed from 1 mg/kg. Highest survival and best preserved kidney function were observed at 3 and 10 mg/kg. Upon treatment with AQGV, a significantly lower influx of neutrophils was found, apoptosis was decreased, whereas tubular epithelial cell proliferation was significantly increased at 24 h post-reperfusion. Serum levels of TNF-{alpha}, INF-{gamma}, IL-6 and IL-10 were significantly decreased at 24 h post-reperfusion. E-selectin mRNA levels in kidneys were significantly decreased at 6 h post-reperfusion. AQGV did not reduce mortality when treatment was started after reperfusion.

Conclusions. This study shows that small oligopeptides related to the primary structure of β-hCG, especially AQGV, are promising potential drugs for preventing the development of renal ischaemia-reperfusion injury.

Keywords: ischaemia reperfusion; kidney; peptide; transplantation


* These authors contributed equally to this paper.

Received for publication: 26. 5.08
Accepted in revised form: 2. 2.09


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