Beneficial effects of recombinant platelet-activating factor acetylhydrolase and BN 52021 on bacterial translocation in cerulein-induced pancreatitis.
BACKGROUND
Bacterial translocation (BT) has been suggested to be responsible for the high incidence of infections occurring after acute pancreatitis (AP). The aim of this study was to investigate the effects of the platelet-activating factor (PAF) inactivator, recombinant PAF-acetylhydrolase (rPAF-AH), and the PAF receptor antagonist, BN 52021, in AP.


METHODS
Forty-eight male Wistar rats were divided into 4 groups: the sham group received saline intraperitoneally every hour for 6 h; the control group received cerulein 50 g/kg i.p. every hour for 6 h; the rPAF-AH group received AP plus rPAF-AH (5 mg/kg i.v. bolus), and the BN52021 group received AP plus BN 52021 (5 mg/kg i.v. bolus). The animals were sacrificed 12 h after the first cerulein injection.


RESULTS
Supramaximal cerulein stimulation induced an increase in serum pancreatic enzymes, interleukin (IL)-6, pancreatic edema, and produced histologic evidence of AP. Compared with the control group, the addition of PAF receptor antagonists had a significant effect on serum pancreatic enzymes, pancreatic edema, and the histologic score of the pancreatitis. AP caused significant increases in BT in mesenteric lymph nodes (MLNs), pancreas, liver, spleen and blood. Compared with the control group, both rPAF-AH and BN 52021 decreased BT in the pancreas and blood. In addition, rPAF-AH decreased BT in the MLNs. We also found that PAF receptor antagonists suppressed the elevation in IL-6 levels.


CONCLUSIONS
PAF antagonists attenuated the severity of experimental AP and reduced pancreatitis-induced BT to distant sites.
Bedirli
A
A
Department of Surgery, Gazi University, Faculty of Medicine, Ankara, Turkey. bedirlia@gazi.edu.tr
Gokahmetoglu
S
S
Sakrak
O
O
Soyuer
I
I
Ince
O
O
Sozuer
E
E
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000627:therapeutic use*; D000208:Acute Disease; D000818:Animals; D001419:Bacteria / Q000302:isolation & purification; D002108:Ceruletide / Q000633:toxicity; D004064:Digestive System / Q000382:microbiology; D004224:Diterpenes / Q000627:therapeutic use*; D046934:Ginkgolides; D007783:Lactones / Q000627:therapeutic use*; D008297:Male; D010195:Pancreatitis / Q000139:chemically induced / Q000188:drug therapy* / Q000382:microbiology*; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors; D011994:Recombinant Proteins / Q000627:therapeutic use
D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones; D010980:Platelet Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled; D011994:Recombinant Proteins; C039351:platelet activating factor receptor; D002108:Ceruletide; C045856:ginkgolide B; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase