Original communication| Volume 109, ISSUE 5, P656-662, May 1991

Long-term cholesterol feeding stimulates increased bile phospholipids and gallbladder prostanoid synthesis

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      The effect of long-term cholesterol feeding on male rabbit gallbladder prostanoid synthesis and bile phospholipid and bile acid levels was examined. In rabbits fed a 2% cholesterol diet for 2, 5, 7, 9, 12, 15, 18, and 21 weeks, serum cholesterol levels increased 12-fold or higher (68-fold at 21 weeks) when compared to the control levels. Total prostanoid synthesis was significantly increased at 7 weeks or more of cholesterol feeding with 6-keto PGF (PGI2 metabolite) and PGE2 as the major products. By 21 weeks of cholesterol feeding, 6-keto PGF and PGE2 levels were increased 15-fold and 11-fold higher, respectively, compared to the control. Total bile phospholipid levels were significantly increased at 12 weeks or more of cholesterol feeding, and total bile acids significantly increased only from 5 through 12 weeks of cholesterol feeding. These data show that long-term feeding male rabbits with a 2% cholesterol diet increased endogenous gallbladder prostanoid synthesis, which was associated with an increase in bile phospholipid levels. Increased rabbit gallbladder bile phospholipids may represent a compensation of the animal for toxic levels of tissue and bile cholesterol. Increased phospholipid levels in the bile or tissue could serve as a source of increased availability of arachidonic acid leading to a nonspecific increase in gallbladder prostanoid synthesis.
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        • Nakata K
        • Osumi Y
        • Fujiwara M
        Prostaglandins and the contractibility of the guinea pig biliary system.
        Pharmacology. 1981; 22: 24-30
        • Heintze K
        • Leinesser W
        • Peterson K
        • Heidenreich O
        Triphasic effect of prostaglandins E1, E2, F2, and pentagastrin on the gallbladder pressure in dogs.
        Eur J of Pharmacol. 1975; 30: 107-112
        • Leyssac P
        • Bukhave K
        • Frederiksen O
        Inhibitory effect of prostaglandins on isosmotic fluid transport by rabbit gallbladder in vitro and its modification by blockade of endogenous PGE-biosynthesis with indomethacin.
        Acta Physiol Scand. 1974; 92: 456-507
        • Myers SI
        • Cheung LY
        Prostacyclin (PGI2) biosynthesis and its effect on luminal fluid absorption in gallbladder.
        Surg Forum. 1984; 35: 229-230
        • Thornell E
        • Svanvik J
        • Wood JR
        Effects of intra-arterial prostaglandin E2 on gallbladder fluid transport, motility and hepatic bile flow in the cat.
        Scand J Gastroenterol. 1981; 16: 1083-1088
        • LaMont JT
        • Turner BS
        • Dibenedetto D
        • et al.
        Arachidonic acid stimulates mucin secretion in prairie dog.
        Am J Physiol. 1983; 245: G92-G98
        • Kuckenbecker SL
        • Doty JE
        • Pitt HA
        • Denbesten L
        Salicylate prevents gallbladder stasis and cholesterol gallstones in the prairie dog.
        Surg Forum. 1981; 32: 154-155
        • Lee SP
        • Carey MC
        • LaMont JT
        Aspirin prevention of cholesterol gallstone formation in prairie dogs.
        Science. 1985; 211: 1429-1450
        • La Morte WW
        • Booker ML
        • Scott TF
        • Williams LF
        Increases in gallbladder prostaglandin synthesis before the formation of cholesterol gallstones.
        Surgery. 1985; 98: 445-451
        • Myers SI
        • Haley-Russell D
        • Parks L
        Elevated prostaglandin production and mucus hypersecretion following rabbit bile duct ligation.
        Gastroenterology. 1987; 5 ([Abstract]): 1547
        • Myers SI
        • Parks L
        The role of inflammation on male and female rabbit gallbladder biosynthesis.
        Gastroenterology. 1987; 5: 1548
        • Myers SI
        • Thomasson D
        • Davis BB
        • Rettke C
        • Park L
        The role of inflammatory cells in enhanced rabbit gallbladder prostaglandin biosynthesis.
        Surg Forum. 1987; 3 ([Abstract]): 180-182
        • Myers SI
        • Parks L
        Indomethacin inhibition of abnormal gallbladder in vitro fluid absorption in a rabbit model of early acute cholecystitis.
        Surg Forum. 1988; 39: 156-158
        • Thornell E
        • Jivegard L
        • Bukhaus K
        • Rask-Modsen J
        • Sanvik J
        Prostaglandin D2 formation by the gallbladder in experimental cholecystitis.
        Gut. 1986; 27: 370-373
        • Kaminski DL
        • Deshparde YG
        • Quely J
        • Thomas LA
        The role of prostaglandins in feline experimental cholecystitis.
        Surgery. 1985; 98: 760-767
        • Myers SI
        • Zipser RA
        • Needleman P
        Exaggerated prostaglandin and thromboxane synthesis in the constricted renal vein of a rabbit.
        in: Samuelsson B Ramwell P Paoletti R Advances in prostaglandin and thromboxane research. Raven Press, New York1980: 1171
        • Zipser RA
        • Myers SI
        • Needleman P
        Exaggerated prostaglandin and thromboxane synthesis in the renal vein constricted rabbit kidney modulators of renal resistance.
        Circ Res. 1980; 47: 231
        • Myers SI
        Effect of estrogen on rabbit gallbladder prostaglandin biosynthesis.
        J Surg Res. 1985; 38: 630-634
        • Myers SI
        • Parks L
        • Smith G
        • Miller TA
        Elevated PGI2 and PGE2 production in the rat ileum following mild hypotension.
        J Trauma. 1988; 28: 1202-1206
        • Myers SI
        • Parks L
        Effects of sex hormones on rabbit gallbladder prostaglandin biosynthesis.
        J Surg Res. 1988; 45: 154-157
        • Morrison AR
        • Moritz H
        • Needleman P
        Mechanism of enhanced renal prostaglandin biosynthesis in ureter obstruction: role of de novo protein synthesis.
        J Biol Chem. 1978; 253: 8120-8212
        • Myers SI
        • Zipser R
        • Needleman P
        Peptide-induced prostaglandin biosynthesis in the renal-vein-constricted kidney.
        Biochem J. 1981; 198: 357-363
        • McCluskey FR
        • Corr PB
        • Lee BI
        • Soffitz JE
        • Needleman P
        The arachidonic acid metabolic capacity of canine myocardium is increased during healing of acute myocardial infarction.
        Circ Res. 1982; 51: 743-750
        • Salmon JA
        • Smith DR
        • Flower RJ
        • Moncada S
        • Vane JR
        Further studies on the enzymatic conversion of prostaglandin endoperoxide into prostacyclin by porcine aorta microsomes.
        Biochem et Biophys Acta. 1978; 523: 250-262
        • LeDuc LE
        • Needleman P
        Regional localization of prostacyclin and thromboxane synthesis in dog stomach and intestinal tract.
        J Pharmacol Exp Ther. 1976; 211: 181-188
        • Smith WL
        • Lands WEM
        Oxygenation of polyunsaturated fatty acids during prostaglandin biosynthesis by sheep vesicular glands.
        Biochemistry. 1972; 11: 3276-3285
        • Lysz TW
        • Needleman P
        Evidence for two distinct forms of fatty acid cyclooxygenase in the brain.
        J Neurochem. 1982; 38: 1111-1117
        • Lowry O
        • Rosenbrough N
        • Farr A
        • Randall R
        Protein measurement with the folin phenol reagent.
        J Biol Chem. 1951; 193: 265-275
        • Needleman P
        • Raz A
        • Ferrendelli JA
        • Minkes M
        Application of imidazole as a selective inhibitor of thromboxane synthetase in human platelets.
        in: 2nd ed. Proc National Acad Sci USA. 74. 1977: 1716-1720
        • Eckenfels A
        • Vane JR
        Prostaglandins, oxygen tension and smooth muscle tone.
        Br J Pharmacol. 1972; 45: 451-462
        • Hamberg M
        • Samuelson B
        Prostaglandins in human seminal plasma.
        J Biol Chem. 1966; 241: 257-263
        • Nugteren DH
        • Hlazelhof E
        Isolation and properties of intermediates in prostaglandin biosynthesis.
        Biochem Biophys Acta. 1973; 326: 448-461
      1. Ellefson RD Caraway WT Tietiz NW Fundamentals of clinical chemistry. 2nd ed. WB Saunders Co, Philadelphia1976: 506-509
        • Muraca M
        • Yvo G
        Glyco-7a,12a-dihydroxy-5B-cholanic acid as internal standard for high-pressure liquid chromatographic analysis of conjugated bile acids.
        J Lipid Res. 1985; 26: 1009-1011
        • Folch J
        • Lees M
        • Sloane S
        A simple method for the isolation and purification of total lipids from animal tissues.
        J Biol Chem. 1957; 226: 497-509
        • Dugan EA
        Analysis of phospholipids by one-dimensional thin-layer chromatography.
        Liquid Chromatography. 1985; 3: 126-128
        • Johnson J
        • Kalant N
        Bile composition in the pregnant rabbit.
        Dig Dis. 1972; 17: 1-6
        • England DW
        • Jaffe BM
        • Webb H
        • Hoover EL
        The prostaglandin response to cholesterol feeding by the rabbit gallbladder in vitro.
        Surgery. 1988; 103: 69-73
        • Altman RFA
        • Schaeffer MV
        • Salles CA
        • Ramos de Souza AS
        • Cotros PMT
        Phospholipids associated with vitamin C in experimental atherosclerosis.
        Arzneim-Forsch/Drug Research. 1980; 30: 627-630
        • Garg ML
        • Sabine JR
        Homeostatic control of membrane cholesterol and fatty acid metabolism in the rat liver.
        Biochem J. 1988; 251: 11-16
        • Berlin E
        • Shapiro SG
        • Kliman PG
        Influence of saturated and unsaturated fats on platelet fatty acids in cholesterol-fed rabbits.
        Atherosclerosis. 1987; 63: 85-96
        • Booker ML
        • Scott TE
        • La Morte WW
        Effect of dietary cholesterol on phosphatidylcholines and phosphatidylethanolamines in bile and gallbladder mucosa in the prairie dog.
        Gastroenterology. 1989; 97: 1261-1267
        • Schouten JA
        • Beyner AC
        • Popp-Snijders C
        • Mulder C
        • Blitterswick WJ
        • Hoitsma HFW
        The composition of plasma lipoproteins and erythrocyte membranes in cholesterol-fed pigs with partial ileal bypass.
        Artery. 1987; 14: 165-189