An oral platelet-activating factor antagonist, Ro-24-4736, protects the rat kidney from ischémie injury

K. J. Kelly, Nina E. Tolkoff-Rubin, Robert H. Rubin, Winfred W. Williams, Shane M. Meehan, Carol L. Meschter, James G. Christenson, Joseph V. Bonventre

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40 Scopus citations

Abstract

The role of platelet-activating factor (PAF) in ischémie 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 was less pronounced when compared with postischemic kidneys from vehicle-treated animals. Serum creatinine (mg/ dl) 24 h following renal ischemia was 1.58 0.17 in the PAF antagonist-treated rats compared with 2.19 0.15 in rats given placebo (P 0.01). 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 h 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 2 h following the ischémie insult. The coincident use of anti-intercellular adhesion molecule-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 ischémie injury, perhaps by its effects on leukocyte-endothelial interactions. An orally active PAF antagonist can protect against the development of ischémie acute renal failure. acute renal failure; ischemia-reperfusion injury; phospholipid mediators; leukocyte adhesion; animal models

Original languageEnglish (US)
Pages (from-to)F1061-F1067
JournalAmerican Journal of Physiology
Volume271
Issue number5 PART 2
StatePublished - Dec 1 1996
Externally publishedYes

ASJC Scopus subject areas

  • Physiology (medical)

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    Kelly, K. J., Tolkoff-Rubin, N. E., Rubin, R. H., Williams, W. W., Meehan, S. M., Meschter, C. L., Christenson, J. G., & Bonventre, J. V. (1996). An oral platelet-activating factor antagonist, Ro-24-4736, protects the rat kidney from ischémie injury. American Journal of Physiology, 271(5 PART 2), F1061-F1067.