Cholesterol crystals enhance and phospholipids protect against pancreatitis induced by hydrophobic bile salts: a rat model study.
OBJECTIVE
The role of bile composition in the pathogenesis of biliary pancreatitis is unknown. The objective of this experiment was to explore the potential role of bile salts, phospholipids, and cholesterol crystals in the pathogenesis of biliary pancreatitis in a rat model.


METHODS
Model systems composed of taurodeoxycholate (TDC), mixed bile salts (MBS), or tauroursodeoxycholate (TUDC) [in 10 mM phosphate-buffered saline (PBS), pH 7.4], with or without cholesterol crystals or phosphatidylcholine, were infused into bile ducts of male Sprague-Dawley rats. Twenty-four hours later, animals were killed for histopathologic scoring of (peri)pancreatic inflammation.


RESULTS
: Severity of acute pancreatitis depended on bile salt hydrophobicity (TDC > MBS >> TUDC = PBS; histopathologic scores: 25.6 +/- 0.5, 23.0 +/- 1.5, 14.4 +/- 2.2, 14.8 +/- 1.0, respectively; P < 0.001), with corresponding differences in serum lipase concentration. Phosphatidylcholine protected against detrimental effects of TDC at physiological, but not at low, concentrations (scores: 19.5 +/- 2.3 vs 28.3 +/- 1.9 in case of Phosphatidycholine/(TDC + Phosphatidycholine) ratios 0.25 or 0.05, respectively). Cholesterol crystals increased severity of pancreatitis in model systems containing TDC or MBS, but not TUDC or PBS (33.2 +/- 0.4, 29.6 +/- 1.2, 18.6 +/- 1.5, 18.5 +/- 2.2, respectively; P < 0.001).


CONCLUSIONS
In the rat model, hydrophobic bile salts and cholesterol crystals aggravate biliary pancreatitis, whereas phospholipids have a protective effect.
van Minnen
L Paul
LP
Gastrointestinal Research Unit, Departments of Gastroenterology and Surgery, University Medical Center Utrecht, The Netherlands. K.J.vanerpecum@azu.nl
Venneman
Niels G
NG
van Dijk
Jaap E
JE
Verheem
André
A
Gooszen
Hein G
HG
Akkermans
Louis M A
LM
van Erpecum
Karel J
KJ