AN ORAL PLATELET-ACTIVATING-FACTOR ANTAGONIST, RO-24-4736, PROTECTS THE RAT-KIDNEY FROM ISCHEMIC-INJURY

The role of platelet-activating factor (PAF) in ischemic acute renal f ailure was evaluated by administering an oral PAF antagonist (Re-24-47 36) to rats prior to or after interruption of blood flow to both kidne ys for 30 min. In animals treated with the PAF antagonist prior to isc hemia, renal function was less impaired and histological abnormalities was less pronounced when compared with postischemic kidneys from vehi cle-treated animals. Serum creatinine (mg/dl) 24 h following renal isc hemia was 1.58 +/- 0.17 in the PAF antagonist-treated rats compared wi th 2.19 +/- 0.15 in rats given placebo (P < 0.01). There was less necr osis in the outer medulla of kidneys of PAF antagonist-treated animals (P < 0.01). Tissue myeloperoxidase activity at 48 and 72 h postisch e mia was lower in kidneys of PAF antagonist-treated rats (P < 0.05). Th e PAF antagonist was also protective when administered 30 min but not 2 h following the ischemic insult. The coincident use of anti-intercel lular adhesion molecule-1 monoclonal antibody did not confer additiona l protection over that observed with the oral PAF antagonist alone. Th ese data suggest that PAF contributes to the pathophysiology of renal ischemic injury, perhaps by its effects on leukocyte-endothelial inter actions. An orally active PAF antagonist can protect against the devel opment of ischemic acute renal failure.