Effect of PAF antagonists on cerulein-induced pancreatitis.
The present study was undertaken to investigate the involvement of PAF in acute pancreatitis induced by cerulein in rats. Cerulein (two doses of 20 micrograms/rat, the first s.c. and the second i.v., 1 h apart) induced a significant increase in vascular permeability in the pancreas, evaluated by the Evans blue (EB) extravasation method. Plasma amylase levels were also significantly increased in this group. The PAF antagonists, BN-52021 (5 mg/kg) and WEB-2170 (1 and 10 mg/kg), both significantly reduced the extravasation of EB in the pancrease induced by i.v. injection of PAF (1 microgram/kg). At these concentrations, BN-52021 was effective at inhibiting cerulein-induced pancreatitis (60-70% of inhibition) whereas WEB-2170 had no significant effect. Although the inhibition induced by BN-52021 suggests the involvement of PAF in cerulein-pancreatitis, the lack of effect of WEB-2170 reported here does not allow a definite conclusion. Further studies are needed to elucidate the differential effect of the PAF antagonists.
Jancar
S
S
Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, Brazil.
Abdo
E E
EE
Sampietre
S N
SN
Kwasniewski
F H
FH
Coelho
A M
AM
Bonizzia
A
A
Machado
M C
MC
D000208:Acute Disease; D000681:Amylases / Q000097:blood; D000818:Animals; D001381:Azepines / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects; D002108:Ceruletide / Q000633:toxicity*; D004224:Diterpenes; D005070:Evans Blue / Q000493:pharmacokinetics; D046934:Ginkgolides; D007783:Lactones / Q000494:pharmacology*; D008297:Male; D010179:Pancreas / Q000098:blood supply; D010195:Pancreatitis / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar; D014230:Triazoles / Q000494:pharmacology*
D001381:Azepines; D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones; D010972:Platelet Activating Factor; D014230:Triazoles; D005070:Evans Blue; D002108:Ceruletide; C063964:bepafant; C045856:ginkgolide B; D000681:Amylases