The platelet-activating factor receptor antagonist WEB 2170 prevents neonatal necrotizing enterocolitis in rats.
To evaluate the role of platelet-activating factor (PAF) in a neonatal rat model of necrotizing enterocolitis (NEC).


METHODS
NEC was reproduced in newborn rats following exposure to formula feeding, asphyxia, and bacterial colonization. The role of endogenous PAF in neonatal NEC was studied by pretreating animals with PAF receptor antagonists (WEB 2170 and WEB 2086) and by measuring intestinal PAF content in animals with NEC, WEB-treated animals, and controls.


RESULTS
We found that WEB 2170 (dosed using 10 mg/kg in a.m. and 30 mg/kg in p.m.) markedly reduced the incidence of NEC (3/17 vs. 14/18 control: p < 0.001) and death (6/17 vs. 17/18 control; p < 0.001) compared with saline-treated animals. Although lower WEB 2170 doses prevented NEC, neither fourfold higher dosing with WEB 2170 nor similar dosing with WEB 2086 affected the incidence of disease in this study. PAF content in intestine was elevated in NEC animals (270 +/- 80 pg/g) compared with WEB 2170-treated animals (0 pg/g) and maternally fed controls (70 +/- 50 pg/g).


CONCLUSIONS
The data support the role of PAF in the final common pathway of neonatal NEC.
Caplan
M S
MS
Department of Pediatrics, Evanston Hospital, IL 60201, USA.
Hedlund
E
E
Adler
L
L
Lickerman
M
M
Hsueh
W
W
D000818:Animals; D000831:Animals, Newborn; D001381:Azepines / Q000627:therapeutic use*; D004761:Enterocolitis, Pseudomembranous / Q000473:pathology / Q000517:prevention & control*; D007413:Intestinal Mucosa / Q000378:metabolism; D007421:Intestine, Small / Q000473:pathology; D009336:Necrosis; D010972:Platelet Activating Factor / Q000096:biosynthesis; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D014230:Triazoles / Q000627:therapeutic use*
D001381:Azepines; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D014230:Triazoles; C039351:platelet activating factor receptor; C063964:bepafant