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


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 nitroprusside 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%+/-2.8% 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.
Goor
Yoav
Y
Department of Internal Medicine 6, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. goorfam@green.co.il
Goor
Odelia
O
Wollman
Yoram
Y
Chernichovski
Tamara
T
Schwartz
Doron
D
Cabili
Shaltiel
S
Iaina
Adrian
A
D058186:Acute Kidney Injury / Q000201:enzymology* / Q000503:physiopathology; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D004195:Disease Models, Animal; D004789:Enzyme Activation; D007677:Kidney Function Tests; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects*; D008297:Male; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000187:drug effects; D009599:Nitroprusside / Q000494:pharmacology*; D009195:Peroxidase / Q000187:drug effects / Q000378:metabolism*; D011134:Polysaccharides / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D012680:Sensitivity and Specificity; D016482:Urinalysis
D011134:Polysaccharides; D012333:RNA, Messenger; D009599:Nitroprusside; C007789:fucoidan; D009195:Peroxidase; D019001:Nitric Oxide Synthase