Octreotide increases the proportions of arachidonic acid‐rich phospholipids in gall‐bladder bile

Abstract

Background and aims: Octreotide treatment of acromegalic patients induces cholesterol gallstone formation, in part by impairing cholecystokinin release and gall‐bladder contraction. However, there are few data on the effect of octreotide on biliary arachidonic acid‐rich phospholipids or mucin glycoprotein, factors which also influence cholesterol gallstone formation. Methods: In acromegalic patients studied before and during 3 months of octreotide treatment, we measured mucin glycoprotein concentrations and the molecular species of phosphatidylcholine, and related the results to the cholesterol saturation and percentage of deoxycholic acid in gall‐bladder bile. Results: The relative proportions of the major arachidonic acid‐rich phosphatidylcholine species, PC 16:0–20:4 and PC 18:0–20:4, increased significantly during octreotide treatment. These changes were associated with a rise in the cholesterol saturation index and a non‐significant twofold increase in mucin glycoprotein concentration. There were significant correlations between PC 16:0–20:4 and the cholesterol saturation index, percentage of vesicular cholesterol and percentage of deoxycholic acid in gall‐bladder bile. Conclusions: In acromegalic patients, octreotide increases the proportions of arachidonic acid‐rich phospholipids, with associated rises in: (a) the cholesterol saturation index and percentage of vesicular cholesterol, and (b) the percentage of deoxycholic acid in gall‐bladder bile—changes similar to those found in patients with cholesterol‐rich gall‐bladder stones.

Bile composition in inflammatory bowel disease: ileal disease and colectomy, but not colitis, induce lithogenic bile

“… 49 In turn, this increase in arachidonic acid‐rich phospholipids has been shown to promote biliary cholesterol supersaturation, destabilize cholesterol carriers and induce mucin glycoprotein synthesis 50 . In the present study, the proportions of arachidonic acid‐rich phosphatidylcholine species in the bile of patients with active Crohn's disease were similar to those in patients with cholesterol‐rich gallstones, and higher than those in the bile of historical controls (stone‐free patients with acromegaly untreated with octreotide) reported previously 13 . We did not detect a difference in phosphatidylcholine composition between the three Crohn's disease sub‐groups although, given their relatively small size, it is possible that this may represent a type II error.…”

“…We did not detect a difference in phosphatidylcholine composition between the three Crohn's disease sub‐groups although, given their relatively small size, it is possible that this may represent a type II error. Furthermore, unlike some previous reports of a positive correlation between biliary deoxycholic acid and arachidonic acid‐rich phospholipids in patients with cholesterol‐rich gallstones, 51 or octreotide‐induced gallstones, 13 we found no such relationship in the current study — similar to findings in two comparative studies of patients with pigment‐ and cholesterol‐rich gallstones 52 ,. 53 …”

“…The concentrations of the individual bile acid conjugates were determined using reverse‐phase high‐performance liquid chromatography, 19 and expressed as percentages of total conjugated bile acids. Following Fölch extraction of the lipid phase of gall‐bladder bile, phosphatidylcholine was separated from the other biliary lipids by high‐performance liquid chromatography, and the molecular species of the separated phosphatidylcholine were determined by reverse phase high‐performance liquid chromatography 13 . Results were compared with those obtained from a group of 13 patients (10 women, three men; mean age, 45 years; range, 31–69 years) with ‘conventional’ cholesterol‐rich gallstone disease, in whom gall‐bladder bile was obtained either by fine‐needle aspiration during elective cholecystectomy ( n = 4) or by ultrasound‐guided percutaneous transhepatic fine‐needle puncture ( n = 9), as previously described 20 .…”

“…The aims of the present study, therefore, were to determine the cholesterol saturation indices (CSIs), microcrystal nucleation times and total bilirubin concentrations in fresh gall‐bladder bile of patients with ileal or colonic Crohn's disease and those who had undergone colonic resection, and to compare these values with those from a group of patients with active ulcerative colitis, or who were post‐colectomy. In a sub‐group of patients with Crohn's disease and in a group of disease controls, we also determined the biliary bile acid composition and the molecular species of biliary phosphatidylcholine (the principal phospholipid in bile), factors which are known to influence cholesterol microcrystal nucleation and gallstone formation 13 …”

Octreotide Inhibits the Bilirubin Carriers Organic Anion Transporting Polypeptides 1B1 and 1B3 and the Multidrug Resistance-Associated Protein 2

“…Octreotide is also employed as a radioligand for the imaging and treatment of somatostatin receptorexpressing tumors (i.e., neuroendocrine tumors) (Toumpanakis and Caplin, 2013). Octreotide is mainly cleared into bile in unchanged form (Berelowitz et al, 1978;Bauer et al, 1982;Lemaire et al, 1989) and can lead to hyperbilirubinemia and asymptomatic gallbladder stone formation, albeit without signs of liver injury (Arosio et al, 1988;Hussaini et al, 1994;Radetti et al, 2000;Crook and Steger, 2001;Pereira et al, 2001;Koren et al, 2013). Nevertheless, the mechanism of the vectorial transport of octreotide from portal blood into bile has been only partially studied with conflicting results and none has investigated the interaction of octreotide with the main human liver transporters (Terasaki et al, 1995;Yamada et al, 1996Yamada et al, , 1997Gutmann et al, 2000).…”