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

Nisar Khan, D Susa, Jan Willem Berg, M Huisman, MH (Miriam) Ameling, Sandra Engel, Henk Roest, J.N.M. IJzermans, Wim Dik, Rob Benner, Ron de Bruin

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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 beta-hCG, especially AQGV, are promising potential drugs for preventing the development of renal ischaemia-reperfusion injury.
Original languageUndefined/Unknown
Pages (from-to)2701-2708
Number of pages8
JournalNephrology Dialysis Transplantation
Issue number9
Publication statusPublished - 2009

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