title: Amelioration of renal ischaemia-reperfusion injury by synthetic oligopeptides related to human chorionic gonadotropin.
abstract: 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.
authors.affiliation: Department of Immunology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
authors.forename: Nisar A
authors.initials: NA
authors.lastname: Khan
authors.forename: Denis
authors.initials: D
authors.lastname: Susa
authors.forename: Jan Willem
authors.initials: JW
authors.lastname: van den Berg
authors.forename: Martin
authors.initials: M
authors.lastname: Huisman
authors.forename: Miriam H
authors.initials: MH
authors.lastname: Ameling
authors.forename: Sandra
authors.initials: S
authors.lastname: van den Engel
authors.forename: Henk P
authors.initials: HP
authors.lastname: Roest
authors.forename: Jan N M
authors.initials: JN
authors.lastname: Ijzermans
authors.forename: Willem A
authors.initials: WA
authors.lastname: Dik
authors.forename: Robbert
authors.initials: R
authors.lastname: Benner
authors.forename: Ron W F
authors.initials: RW
authors.lastname: de Bruin
mesh_terms: 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*
chemical_list: D018997:Chorionic Gonadotropin, beta Subunit, Human; D016207:Cytokines; D009842:Oligopeptides; D012333:RNA, Messenger