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

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

Research output: Contribution to journalArticle

40 Citations (Scopus)

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)
JournalAmerican Journal of Physiology - Renal Physiology
Volume271
Issue number5 PART 2
StatePublished - 1996
Externally publishedYes

Fingerprint

Platelet Activating Factor
Kidney
Wounds and Injuries
Acute Kidney Injury
Leukocytes
Ischemia
Ro 24-4736
Kidney Medulla
Intercellular Adhesion Molecule-1
Reperfusion Injury
Peroxidase
Creatinine
Phospholipids
Necrosis
Animal Models
Monoclonal Antibodies
Placebos

ASJC Scopus subject areas

  • Physiology (medical)
  • Physiology

Cite this

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

An oral platelet-activating factor antagonist, Ro-24-4736, protects the rat kidney from ischémie injury. / Kelly, Katherine; Tolkoff-Rubin, Nina E.; Rubin, Robert H.; Williams, Winfred W.; Meehan, Shane M.; Meschter, Carol L.; Christenson, James G.; Bonventre, Joseph V.

In: American Journal of Physiology - Renal Physiology, Vol. 271, No. 5 PART 2, 1996.

Research output: Contribution to journalArticle

Kelly, K, Tolkoff-Rubin, NE, Rubin, RH, Williams, WW, Meehan, SM, Meschter, CL, Christenson, JG & Bonventre, JV 1996, 'An oral platelet-activating factor antagonist, Ro-24-4736, protects the rat kidney from ischémie injury', American Journal of Physiology - Renal Physiology, vol. 271, no. 5 PART 2.
Kelly, Katherine ; Tolkoff-Rubin, Nina E. ; Rubin, Robert H. ; Williams, Winfred W. ; Meehan, Shane M. ; Meschter, Carol L. ; Christenson, James G. ; Bonventre, Joseph V. / An oral platelet-activating factor antagonist, Ro-24-4736, protects the rat kidney from ischémie injury. In: American Journal of Physiology - Renal Physiology. 1996 ; Vol. 271, No. 5 PART 2.
@article{7b9e1b7d0b2649748808ffdee5a64f49,
title = "An oral platelet-activating factor antagonist, Ro-24-4736, protects the rat kidney from isch{\'e}mie injury",
abstract = "The role of platelet-activating factor (PAF) in isch{\'e}mie 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 isch{\'e}mie 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 isch{\'e}mie injury, perhaps by its effects on leukocyte-endothelial interactions. An orally active PAF antagonist can protect against the development of isch{\'e}mie acute renal failure. acute renal failure; ischemia-reperfusion injury; phospholipid mediators; leukocyte adhesion; animal models",
author = "Katherine Kelly and Tolkoff-Rubin, {Nina E.} and Rubin, {Robert H.} and Williams, {Winfred W.} and Meehan, {Shane M.} and Meschter, {Carol L.} and Christenson, {James G.} and Bonventre, {Joseph V.}",
year = "1996",
language = "English (US)",
volume = "271",
journal = "American Journal of Physiology",
issn = "0193-1857",
publisher = "American Physiological Society",
number = "5 PART 2",

}

TY - JOUR

T1 - An oral platelet-activating factor antagonist, Ro-24-4736, protects the rat kidney from ischémie injury

AU - Kelly, Katherine

AU - Tolkoff-Rubin, Nina E.

AU - Rubin, Robert H.

AU - Williams, Winfred W.

AU - Meehan, Shane M.

AU - Meschter, Carol L.

AU - Christenson, James G.

AU - Bonventre, Joseph V.

PY - 1996

Y1 - 1996

N2 - 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

AB - 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

UR - http://www.scopus.com/inward/record.url?scp=0029853672&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029853672&partnerID=8YFLogxK

M3 - Article

C2 - 8946001

AN - SCOPUS:0029853672

VL - 271

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 0193-1857

IS - 5 PART 2

ER -