Fucoidin, an inhibitor of leukocyte adhesion, exacerbates acute ischemic renal failure and stimulates nitric oxide synthesis

Yoav Goor*, Odelia Goor, Yoram Wollman, Tamara Chernichovski, Doron Schwartz, Shaltiel Cabili, Adrian Iaina

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Objectives. To lessen renal ischemic injury caused by fucoidin, a substance capable of reducing tissue infiltration by neutrophils, and to seek a possible interrelationship with the nitric oxide system which may also modulate leukocyte infiltration. Material and methods. Acute ischemic renal failure was induced in rats by uninephrectomy followed by 60 min of clamping of the renal artery. The rats were injected with fucoidin (25 mg/kg) or fucoidin+nitroprusside (2.5 mg/kg) before reperfusion, and urine was collected for 24 h afterwards. Serum and urine were examined for creatinine sodium and protein; creatinine clearance and fractional excretion of sodium (FENa) were calculated. The renal tissue of the sacrificed animals was examined histologically for tissue damage and histochemically for myeloperoxidase, a marker of neutrophil infiltration. The nitric oxide system was evaluated by measuring urinary nitrates and inducible nitric oxide synthase messenger RNA (iNOs mRNA). Results. Renal failure was more severe in the fucoidin group than the ischemia only group (creatinine clearance 0.11±0.08 ml/min for ischemia+fucoidin versus 0.26±0.11 ml/min for ischemia only; p <0.002). Adding nitroprusside to fucoidin lessened the decline in creatinine clearance (0.13±0.13 ml/min; p=NS). Fucoidin was associated with greater tubular damage, as evidenced by increased FENa (7.2%±3.4% vs 1.51%±1.96% for ischemia only; p <0.001). Nitroprusside weakened this trend. Fucoidin caused an increase in the fractional excretion of nitrates, a response accompanied by increased iNOS mRNA. Conclusions. Fucoidin failed to protect the kidney from ischemic damage and was even nephrotoxic. It also stimulated the formation of iNOS RNA.

Original languageEnglish
Pages (from-to)57-62
Number of pages6
JournalScandinavian Journal of Urology and Nephrology
Volume40
Issue number1
DOIs
StatePublished - Jan 2006

Keywords

  • Acute ischemic renal failure
  • Fucoidin
  • Leukocyte rolling

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