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 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 ischemic 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 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.
Kelly
K J
KJ
Medical Service, Massachusetts General Hospital, Boston, USA.
Tolkoff-Rubin
N E
NE
Rubin
R H
RH
Williams
W W
WW
Meehan
S M
SM
Meschter
C L
CL
Christenson
J G
JG
Bonventre
J V
JV
D058186:Acute Kidney Injury / Q000473:pathology; D000284:Administration, Oral; D000818:Animals; D000906:Antibodies / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology; D007511:Ischemia / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D007668:Kidney / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D010617:Phenanthridines / Q000008:administration & dosage / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation; D015424:Reperfusion; D014227:Triazines / Q000008:administration & dosage / Q000494:pharmacology*
D000906:Antibodies; D010617:Phenanthridines; D010972:Platelet Activating Factor; D014227:Triazines; C071318:Ro 24-4736; D018799:Intercellular Adhesion Molecule-1; D009195:Peroxidase