Amelioration of renal ischaemia-reperfusion injury by synthetic oligopeptides related to human chorionic gonadotropin
Nephrology, Dialysis, Transplantation , Volume 24 - Issue 9 p. 2701- 2708
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 mgkg. A survival gain was observed with all doses. Improvement of kidney function was observed from 1 mgkg. Highest survival and best preserved kidney function were observed at 3 and 10 mgkg. 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-α, INF-γ, 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.
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|Nephrology, Dialysis, Transplantation|
|Organisation||Erasmus MC: University Medical Center Rotterdam|
Khan, N.A, Susa, D, van den Berg, J.W, Huisman, M, Ameling, M.H, van den Engel, S, … de Bruin, R.W.F. (2009). Amelioration of renal ischaemia-reperfusion injury by synthetic oligopeptides related to human chorionic gonadotropin. Nephrology, Dialysis, Transplantation, 24(9), 2701–2708. doi:10.1093/ndt/gfp369