Jm. Barrios et Lm. Lichtenberger, Role of biliary phosphatidylcholine in bile acid protection and NSAID injury of the ileal mucosa in rats, GASTROENTY, 118(6), 2000, pp. 1179-1186
Background & Aims: We explored the role of biliary phosphatidylcholine (PC)
in protection of the intestinal mucosa against bile salt (BS)-induced inte
stinal injury and how this property may be blocked by indomethacin (Indo),
a nonsteroidal anti-inflammatory drug (MSAID) that is secreted into the bil
e. Methods: We performed in vivo studies in which bile was collected over a
2-hour period after rats were intragastrically administered Indo (25 mg/kg
) or an equivalent volume of saline (controls). The bile samples (some of w
hich were supplemented with PC) were then instilled into a loop of distal i
leum of anesthetized rats. After a 30-minute exposure period, we measured t
he hemoglobin concentration of the ileal loop fluid, as an index of bleedin
g, and mucosal contact angles, as an index of surface hydrophobicity. A sim
ilar in vivo experiment was performed in which model bile containing 5 mmol
/L each of the BS, sodium deoxycholate, PC, or Indo, alone and in combinati
on, was instilled into ileal loops. In our in vitro test system, human eryt
hrocytes were exposed to the above biliary constituents, and hemolysis was
measured spectrophotometrically. Results: Bile from Indo-pretreated rats de
creased the surface hydrophobicity and induced bleeding of ileal loops in c
omparison with control bile, and both NSAID-induced changes were reversed i
f PC was added to the bile. Similarly, synthetic BS caused gastrointestinal
bleeding, decreased ileal contact angles, and induced erythrocyte hemolysi
s, all of which were reversed by addition of equimolar PC. This protective
role of PC in both the in vivo and in vitro systems was partially blocked b
y Indo, although the NSAID had no effect on these properties on its own. Co
nclusions: These findings support the hypothesis that PC protects the intes
tinal mucosa against injurious actions of BS, possibly by forming less toxi
c mixed micelles. Indo and perhaps other NSAIDs that enter the bile may dam
age the mucosa, not by a direct action, but by competing for the available
protective PC molecules.