Fibroblast growth factor protects the kidney against ischemia-reperfusion injury.

Abstract

Ischemia-reperfusion injury, a common source of renal dysfunction in adults, is associated with tubular epithelial cell damage. Since fibroblast growth factors (FGF) attenuated tissue injury after transient myocardial ischemia, we hypothesized that acidic fibroblast growth factor (aFGF; FGF-1) would attenuate renal ischemia-reperfusion injury. We studied the effects of FGF-1 in a rat model of acute renal failure induced by bilateral renal ischemia (60 min) and 1, 2 or 7 days reperfusion. After FGF-1 administration at the onset of renal reperfusion, there was less functional impairment of the kidneys. The histological changes were not as severe as in controls. Increases in serum creatinine and blood urea nitrogen 24 h after reperfusion were attenuated by 35% (p< 0.01) and by 53% (p< 0.001), respectively, in FGF-1-treated animals compared to vehicle-treated rats. The ischemia/reperfusion-induced increase in tissue myeloperoxidase, a marker of neutrophil infiltration, was mitigated (67% reduction, p< 0.05) with FGF-1 treatment. As shown by histology, neutrophil infiltration and tubular cell necrosis in medulla were less pronounced (p< 0.0001 and p< 0.05, respectively) in animals receiving FGF-1. Furthermore, ischemia-induced apoptosis, prevalent in tubular cells of the cortex, was also attenuated by FGF-1-treatment (83% reduction, p< 0.0001). Pretreatment of animals with Nw-nitro-L-arginine (L-NNA), an inhibitor of nitric oxide synthase, abolished the attenuating effects of FGF-1 on neutrophil infiltration, suggesting that nitric oxide might participate in the anti-inflammatory effects of FGF-1 in this experimental design. Our data support a role for FGF-1 in attenuation of renal damage or failure after ischemia-reperfusion injury of the kidney, in part at least by inhibition of neutrophil infiltration.

• Authors: P Cuevas, V Martinez-Coso, X Fu, L Orte, D Reimers, G Giménez-Gallego, W G Forssmann, I Saenz De Tejada
• Journal: European journal of medical research (Eur J Med Res) Vol. 4 Issue 10 Pg. 403-10 (Oct 15 1999) ISSN: 0949-2321 [Print] England
• PMID: 10527953 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Fibroblast Growth Factor 2
• Fibroblast Growth Factor 1
• Peroxidase

Topics

• Animals
• Apoptosis (drug effects)
• Fibroblast Growth Factor 1
• Fibroblast Growth Factor 2 (therapeutic use)
• Ischemia (drug therapy, pathology, physiopathology)
• Kidney (blood supply, drug effects, pathology, physiopathology)
• Peroxidase (metabolism)
• Rats
• Rats, Sprague-Dawley
• Reperfusion Injury (prevention & control)