Amelioration of renal ischaemia-reperfusion injury by synthetic oligopeptides related to human chorionic gonadotropin.
BACKGROUND
We have previously reported that small synthetic oligopeptides related to human beta-chorionic gonadotropin (beta-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 beta-hCG, especially AQGV, are promising potential drugs for preventing the development of renal ischaemia-reperfusion injury.
Khan
Nisar A
NA
Department of Immunology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
Susa
Denis
D
van den Berg
Jan Willem
JW
Huisman
Martin
M
Ameling
Miriam H
MH
van den Engel
Sandra
S
Roest
Henk P
HP
Ijzermans
Jan N M
JN
Dik
Willem A
WA
Benner
Robbert
R
de Bruin
Ron W F
RW
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D016207:Cytokines / Q000097:blood / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000293:injuries*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009842:Oligopeptides / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015427:Reperfusion Injury / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*
D018997:Chorionic Gonadotropin, beta Subunit, Human; D016207:Cytokines; D009842:Oligopeptides; D012333:RNA, Messenger