ANTISENSE OLIGONUCLEOTIDES FOR ICAM-1 ATTENUATE REPERFUSION INJURY AND RENAL-FAILURE IN THE RAT

The leukocyte adhesion molecule ICAM-1 is implicated in ischemic renal reperfusion injury. We tested the utility of an ICAM-1 antisense olig odeoxyribonucleotide (ODN) with lipofectin, six hours prior to 30 minu tes of bilateral renal ischemia in the rat. We measured ICAM-1 express ion by immunohistochemistry and Western blot. Our antisense ODN showed a specific ICAM-1 surface expression inhibition in vitro. We then ass essed ICAM-1 expression, leukocyte infiltration, serum creatinine, ser um 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 O DN treated rats, compared to antisense ODN treated or sham operated ra ts (P < 0.05). Western blotting showed decreased ICAM-1 protein in ant isense 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 qu antitative 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 t hese findings extends beyond ischemic acute renal failure.