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Antisense oligonucleotides for ICAM 1 attenuate reperfusion injury and renal failure in the rat

Item Type:Article
Title:Antisense oligonucleotides for ICAM 1 attenuate reperfusion injury and renal failure in the rat
Creators Name:Haller, H. and Dragun, D. and Miethke, A. and Park, J.K. and Weis, A. and Lippoldt, A. and Gross, V. and Luft, F.C.
Abstract:The leukocyte adhesion molecule ICAM-1 is implicated in ischemic renal reperfusion injury. We tested the utility of an ICAM-1 antisense oligodeoxyribonucleotide (ODN) with lipofectin, six hours prior to 30 minutes of bilateral renal ischemia in the rat. We measured ICAM-1 expression by immunohistochemistry and Western blot. Our antisense ODN showed a specific ICAM-1 surface expression inhibition in vitro. We then assessed ICAM-1 expression, leukocyte infiltration, serum creatinine, serum urea concentration, and renal histology in rats subjected to renal ischemia and controls. Serum creatinine and urea concentrations 12 and 24 hours post-ischemia were increased in saline treated and reverse ODN treated rats, compared to antisense ODN treated or sham operated rats (P < 0.05). Western blotting showed decreased ICAM-1 protein in antisense ODN-treated kidneys, compared to reverse ODN treated and saline treated ischemic controls (P < 0.05). Antisense ODN also ameliorated the ischemia-induced infiltration of granulocytes and macrophages (P < 0.05), and resulted in less cortical renal damage as assessed by a quantitative pathological grading scale (P < 0.05), compared to reverse ODN or saline treatment. Thus, antisense ODN for ICAM-1 protected the kidney against ischemic renal failure. The clinical applicability of these findings extends beyond ischemic acute renal failure.
Keywords:Cell Adhesion, Intercellular Adhesion Molecule-1, Kidney, Acute Kidney Failure, Liposomes, Neutrophils, Antisense Oligonucleotides, Phosphatidylethanolamines, Sprague-Dawley Rats, Reperfusion Injury, Animals, Rats
Source:Kidney International
Publisher:Nature Publishing Group
Page Range:473-480
Date:August 1996
Official Publication:https://doi.org/10.1038/ki.1996.338
PubMed:View item in PubMed

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