An oral platelet activating factor antagonist, ro 24-4736, protects
the rat kidney from ischemic injury.
Kelly, K. J., Nina E. Tolkoff-Rubin, Robert H. Rubin, Winfred W.
Williams, Jr., Shane M. Meehan, Carol L. Meschter, James G.
Christenson, and Joseph V. Bonventre.
Medical and Pathology Services, Massachusetts General Hospital,
Department of Medicine and Pathology, Harvard Medical School, Boston,
MA 02114; Center for Experimental Pharmacology and Therapeutics,
Harvard-Massachusetts Institute of Technology, Division of Health
Sciences and Technology, Cambridge, MA 02139; and Roche Research
Center, Hoffmann La Roche Inc., Nutley, NJ 07110
APStracts 3:0146F, 1996.
The role of platelet activating factor (PAF) in ischemic acute renal
failure was evaluated by administering an oral PAF antagonist (Ro 24
-4736) to rats prior to or after interruption of blood flow to both
kidneys for 30 min. In animals treated with the PAF antagonist prior
to ischemia, renal function was less impaired and histological
abnormalities less pronounced when compared with postischemic kidneys
from vehicle-treated animals. Serum creatinine (mg/dl) 24 hours
following renal ischemia was 1.58 +/- 0.37 in the PAF antagonist
-treated rats compared to 2.19 +/- 0.53 in rats given placebo
(p<0.001). There was less necrosis in the outer medulla of
kidneys of PAF antagonist-treated animals (p<0.01). Tissue
myeloperoxidase activity at 48 and 72 hour postischemia was lower in
kidneys of PAF antagonist-treated rats (p<0.05). The PAF
antagonist was also protective when administered 30 min but not two
hours following the ischemic insult. The coincident use of anti-ICAM
-1 monoclonal antibody did not confer additional protection over that
observed with the oral PAF antagonist alone. These data suggest that
PAF contributes to the pathophysiology of renal ischemic injury,
perhaps by its effects on leukocyte-endothelial interactions. An
orally active PAF antagonist can protect against the development of
ischemic acute renal failure.
Received 14 December 1995; accepted in final form 13 August 1996.
APS Manuscript Number F414-5.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 29 August 1996