title: Combined peri-ischemic administration of Bβ15-42 in treating ischemia reperfusion injury of the mouse kidney.
abstract: The disruption of endothelial integrity is a crucial step for the development of vascular leakage and consequently ischemia-reperfusion injury (IRI). Regarding the molecular cell-cell interaction, the fibrinopeptide Bβ15-42 prevents vascular leakage by stabilizing the inter-endothelial junctions via association with the vascular endothelial-cadherin. In a previous study we showed that a renoprotective effect in early IRI may be achieved by intravenous administration of Bβ15-42 at the time of reperfusion. We now aimed to investigate whether additional pre-ischemic application of Bβ15-42 could enhance this effect. Therefore C57BL/6 mice were subjected to 0.5h bilateral renal ischemia followed by reperfusion. The animals were randomized into 6 groups (n=6): two control groups treated with i.v. administration of NaCl at reperfusion for 0.5h (NaCl 1h) and 2.5h (NaCl 3h), two groups with Bβ15-42 at reperfusion for 0.5h (Bβ(rep) 1h) and 2.5h (Bβ(rep) 3h), and two groups with administration of Bβ15-42 immediately pre-ischemic as well as at reperfusion for 0.5h (Bβ(peri) 1h) and 2.5h (Bβ(peri) 3h). We found that both Bβ(rep) and Bβ(peri) mice displayed reduced early renal damage compared with NaCl treated mice. However, there was no further reduction of the IR damage through added pre-ischemic application of Bβ15-42. Overall, we detected significantly reduced endothelial activation, lower tissue infiltration of neutrophils as well as lower tissue levels of neutrophil gelatinase-associated lipocalin (NGAL) in all mice treated with Bβ15-42 compared to mice treated with NaCl. Our data confirm the renoprotective effect of Bβ15-42 in the early therapeutic treatment of acute kidney injury due to ischemia and reperfusion. However, a combined pre-and post-ischemic administration of Bβ15-42 appears to provide no additional benefit compared with a sole administration at reperfusion.
authors.affiliation: Department of Urology and Paediatric Urology, Philipps-University Marburg, Germany. Electronic address: anja.urbschat@staff.uni-marburg.de.
authors.forename: Anja
authors.initials: A
authors.lastname: Urbschat
authors.affiliation: Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Goethe-University Frankfurt am Main, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Rupprecht
authors.affiliation: Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Goethe-University Frankfurt am Main, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Zacharowski
authors.affiliation: Department of Internal Medicine III, Center of Nephrology, University Hospital Frankfurt, Goethe-University Frankfurt am Main, Germany.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Obermüller
authors.affiliation: Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Goethe-University Frankfurt am Main, Germany.
authors.forename: Bertram
authors.initials: B
authors.lastname: Scheller
authors.affiliation: Department of Cardiac Surgery, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Johannes
authors.initials: J
authors.lastname: Holfeld
authors.affiliation: Department of Cardiac Surgery, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Can
authors.initials: C
authors.lastname: Tepeköylü
authors.affiliation: Department of Urology and Paediatric Urology, Philipps-University Marburg, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Hofmann
authors.affiliation: Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Goethe-University Frankfurt am Main, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Paulus
mesh_terms: D000209:Acute-Phase Proteins / Q000378:metabolism; D000818:Animals; D002199:Capillary Permeability; D002448:Cell Adhesion; D042783:Endothelial Cells / Q000378:metabolism; D005338:Fibrin Fibrinogen Degradation Products / Q000008:administration & dosage*; D007150:Immunohistochemistry; D007249:Inflammation / Q000473:pathology; D007511:Ischemia / Q000188:drug therapy*; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D000071068:Lipocalin-2; D054834:Lipocalins / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000378:metabolism / Q000473:pathology; D015513:Oncogene Proteins / Q000378:metabolism; D010446:Peptide Fragments / Q000008:administration & dosage*; D015427:Reperfusion Injury / Q000188:drug therapy*; D013997:Time Factors
chemical_list: D000209:Acute-Phase Proteins; D005338:Fibrin Fibrinogen Degradation Products; D000071068:Lipocalin-2; D054834:Lipocalins; D015513:Oncogene Proteins; D010446:Peptide Fragments; C033786:fibrinogen Bbeta (15-42); C071332:Lcn2 protein, mouse
keywords: Endothelial dysfunction; FX06; Mouse model; Renal ischemia reperfusion injury; Vascular leak; Vascular permeability