Protoporphyrin IX-Induced Impairment of Biliary Lipid Secretion in the Rat

1989 ◽  
Vol 77 (5) ◽  
pp. 473-478 ◽  
Author(s):  
F. Perez-Barriocanal ◽  
J. G. Redondo-Torres ◽  
G. R. Villanueva ◽  
E. Arteche ◽  
M. M. Berenson ◽  
...  
Keyword(s):  
Body Weight ◽  
Bile Acid ◽  
Bile Flow ◽  
Acid Output ◽  
Total Phospholipid ◽  
Protoporphyrin Ix ◽  
Biliary Secretion ◽  
Canalicular Membrane ◽  
Anaesthetized Rats ◽  
Phospholipid Species

1. In order to gain information on the effect of protoporphyrin IX on changes in the properties of the canalicular plasma membrane, we studied the release of canalicular membrane constituents, namely phospholipids, cholesterol and 5′-nucleotidase, into bile in anaesthetized rats receiving saline or taurocholate (0.5 μmol min−1 100 g−1 body weight) with or without protoporphyrin IX infusion (10 or 20 μg min−1 100 g−1 body weight). 2. Protoporphyrin IX induced an impairment of spontaneous bile flow and of biliary secretion of cholesterol, phospholipids and bile acids. The taurocholate-induced increase in bile acid output was not significantly reduced by protoporphyrin IX at either of the doses used. However, when a cholestatic dose of protoporphyrin IX was infused, the taurocholate-induced bile flow and secretion of lecithin and cholesterol were significantly reduced. 3. Biliary output of phospholipid species other than lecithin did not counterbalance the protoporphyrin IX-induced reduction in biliary lecithin secretion. Biliary outputs of both total phospholipid and lecithin were inhibited by protoporphyrin IX to similar extents. 4. Protoporphyrin IX alone had no effect on the biliary release of 5′-nucleotidase, whereas when it was given with taurocholate, it increased the bile acid-induced biliary output of this enzyme markedly. 5. In summary, these results indicate that protoporphyrin IX impairs the biliary secretion of phospholipids and cholesterol but not that of bile acid. The release of canalicular membrane constituents other than lipids was also modified by protoporphyrin IX.

scholarly journals Short- and long-term effects of biliary drainage on hepatic cholesterol metabolism in the rat

1990 ◽  
Vol 269 (3) ◽  
pp. 781-788 ◽  
Author(s):  
M J Smit ◽  
A M Temmerman ◽  
R Havinga ◽  
F Kuipers ◽  
R J Vonk
Keyword(s):  
Bile Acid ◽  
Bile Flow ◽  
Cholesterol Metabolism ◽  
Acid Output ◽  
Biliary Secretion ◽  
Surgical Trauma ◽  
Hepatic Cholesterol ◽  
Long Term Effects ◽  
Short And Long Term

The present study concerns short- and long-term effects of interruption of the enterohepatic circulation (EHC) on hepatic cholesterol metabolism and biliary secretion in rats. For this purpose, we employed a technique that allows reversible interruption of the EHC, during normal feeding conditions, and excludes effects of anaesthesia and surgical trauma. [3H]Cholesteryl oleate-labelled human low-density lipoprotein (LDL) was injected intravenously in rats with (1) chronically (8 days) interrupted EHC, (2) interrupted EHC at the time of LDL injection and (3) intact EHC. During the first 3 h after interruption of the EHC, bile flow decreased to 50% and biliary bile acid, phospholipid and cholesterol secretion to 5%, 11% and 19% of their initial values respectively. After 8 days of bile diversion, biliary cholesterol output and bile flow were at that same level, but bile acid output was increased 2-3-fold and phospholipid output was about 2 times lower. The total amount of cholesterol in the liver decreased after interruption of the EHC, which was mainly due to a decrease in the amount of cholesteryl ester. Plasma disappearance of LDL was not affected by interruption of the EHC. Biliary secretion of LDL-derived radioactivity occurred 2-4 times faster in chronically interrupted rats as compared with the excretion immediately after interruption of the EHC. Radioactivity was mainly in the form of bile acids under both conditions. This study demonstrates the very rapid changes that occur in cholesterol metabolism and biliary lipid composition after interruption of the EHC. These changes must be taken into account in studies concerning hepatic metabolism of lipoprotein cholesterol and subsequent secretion into bile.

Effect of protoporphyrin IX on ursodeoxycholate-induced hypercholeresis in the rat

1988 ◽  
Vol 75 (6) ◽  
pp. 593-599
Author(s):  
J. J. Garcia-Marin ◽  
J. G. Redondo-Torres ◽  
F. Perez-Barriocanal ◽  
M. M. Berenson
Keyword(s):  
Body Weight ◽  
Bile Acid ◽  
Bile Flow ◽  
Sodium Taurocholate ◽  
Protoporphyrin Ix ◽  
Inhibitory Effect ◽  
Bicarbonate Secretion ◽  
Bile Formation ◽  
Dose Dependent ◽  
Bile Acid Secretion

1. It is known that the perfusion of rat livers with solutions containing protoporphyrin IX induces a decrease in bile flow which is not due to inhibition of bile acid secretion but rather to decreased electrolyte transport into bile. By contrast, ursodeoxycholate induces hypercholeresis, partly due to a marked stimulation of biliary bicarbonate secretion. The aim of the present work was to investigate the effect of protoporphyrin IX on ursodeoxycholate-induced choleresis in anaesthetized male Wistar rats. 2. Protoporphyrin IX infusion at rates of 10, 20 and 40 μg min−1 100 g−1 body weight into the jugular vein induced a dose-dependent inhibitory effect on bile flow as well as on bile acid and electrolyte secretion. The lowest infused rate only induced slight and non-significant changes in spontaneous bile formation and functional variables such as glycaemia, packed cell volume, blood pH, Pco2, Po2 and bicarbonate concentration, and in hepatic carbonic anhydrase activity. It was thus considered as a subtoxic dose. 3. Sodium taurocholate was infused (0.5 μmol min−1 100 g−1 body weight) over the second hour of the lowest dose of protoporphyrin IX infusion. In these rats, no significant changes in bile flow or bile acid and electrolyte secretion were observed as compared with animals receiving sodium taurocholate plus saline solution. 4. Bile acid secretion induced by ursodeoxycholate infusion (1 μmol min−1 100 g−1 body weight) was similar both in rats receiving ursodeoxycholate plus saline solution and in animals infused with this bile acid over the second hour of the lowest dose of protoporphyrin IX infusion. However, bile flow and biliary bicarbonate secretion induced by ursodeoxycholate were markedly impaired (− 43% and − 56%, respectively) by protoporphyrin IX. 5. These results indicate that in the rat, in vivo, protoporphyrin IX impairs bile formation in a dose-dependent manner. They suggest that the mechanism(s) involved in ursodeoxycholate-induced bicarbonate secretion, and hence hypercholeresis, are particularly sensitive to the inhibitory effect of protoporphyrin IX.

scholarly journals Comparative studies on bile flow and biliary lipid excretion after bile-acid loading in normal and partially hepatectomized rats

1995 ◽  
Vol 305 (2) ◽  
pp. 367-371 ◽  
Author(s):  
M Hoshino ◽  
A Hirano ◽  
T Hayakawa ◽  
Y Kamiya ◽  
T Ohiwa ◽  
...  
Keyword(s):  
Bile Acid ◽  
Rat Liver ◽  
Bile Flow ◽  
Acid Output ◽  
Bile Secretion ◽  
Biliary Lipid ◽  
Isolated Perfusion ◽  
Acid Loading ◽  
Second Peak

This study was performed to investigate sequential changes in bile secretion and biliary lipids after taurocholic acid (TCA) loading of regenerating rat liver. TCA was administered intravenously at stepwise-increasing doses to groups of non-operated control and partially hepatectomized rats, 24, 72 and 168 h after surgery. Bile flow, bile-acid output (BAO) and phospholipid output (PLO) (expressed per gram of liver) in partially hepatectomized rats increased more than in the controls. Using an isolated perfusion rat-liver system, TCA infusion was also carried out on groups of non-operated control and hepatectomized rats 72 h after operation. Again bile flow, BAO and PLO (expressed per gram of liver) were significantly higher in the partial hepatectomy case, mirroring the results obtained in vivo. When horseradish peroxidase (HRP) was pulse-loaded in isolated perfusion preparations, the second peak of biliary HRP secretion in hepatectomized rats was significantly higher than in controls. We conclude that increased bile-acid flow in partially hepatectomized rats is dependent upon acceleration of vesicular transport accompanying or following proliferation in regenerating livers.

Effects of Na+ replacement and amiloride on ursodeoxycholic acid-stimulated choleresis and biliary bicarbonate secretion

1987 ◽  
Vol 252 (2) ◽  
pp. G163-G169 ◽  
Author(s):  
J. R. Lake ◽  
R. W. Van Dyke ◽  
B. F. Scharschmidt
Keyword(s):  
Bile Acid ◽  
Ursodeoxycholic Acid ◽  
Bile Flow ◽  
Acid Output ◽  
Fold Increase ◽  
Isolated Perfused Rat Liver ◽  
Bicarbonate Secretion ◽  
Bile Formation ◽  
Li Substitution ◽  
Stimulation Of

In these studies, we have tested the hypothesis that bile acid-dependent bile formation is attributable, in part, to the stimulation of active bicarbonate secretion and have further explored the cellular mechanism(s) possibly involved in this process using the isolated perfused rat liver. Under control conditions, ursodeoxycholic acid (UDCA) infusion (3 mumol/min X 20 min) produced a 3.7-fold increase in bile flow and a 7.4-fold increase in HCO3- output. Amiloride (an inhibitor of Na+-H+ exchange) decreased UDCA-stimulated bile flow by 20.6% and decreased biliary HCO3- output by 24.9% but increased biliary UDCA output by 42.9%. Thus amiloride decreased UDCA choleretic efficiency (microliter UDCA-stimulated bile/mumol UDCA output) by 45% and UDCA-stimulated increase in HCO3- output per unit UDCA secreted by 48%. Substitution of Li+ for Na+ in perfusate virtually abolished (greater than 95% decrease) both the UDCA choleresis and increase in biliary HCO3- output but modestly decreased (39.6%) biliary bile acid output. Li+ substitution thus decreased UDCA choleretic efficiency by 98% and the UDCA-stimulated increase in HCO3- output by 96%. Amiloride had no effect and Li+ substitution produced a modest decrease in basal bile flow (26.0%) and HCO-3 output (33.5%). Neither amiloride nor Li+ substitution significantly affected UDCA uptake by cultured hepatocytes or by perfused liver. Amiloride (1 mM) also decreased taurocholate (TC)-stimulated choleresis by 48.5%, biliary TC output by 7.2%, and the choleretic efficiency of TC by 45%.(ABSTRACT TRUNCATED AT 250 WORDS)

Pre-replicative phase-related changes in bile acid-induced choleresis in the regenerating rat liver

1990 ◽  
Vol 78 (1) ◽  
pp. 55-62 ◽  
Author(s):  
J. J. Garcia-Marin ◽  
P. Regueiro ◽  
J. C. Perez-Antona ◽  
G. R. Villanueva ◽  
F. Perez-Barriocanal
Keyword(s):  
Bile Acid ◽  
Ursodeoxycholic Acid ◽  
Cholic Acid ◽  
Rat Liver ◽  
Bile Flow ◽  
Acid Output ◽  
Liver Weight ◽  
Bicarbonate Secretion ◽  
Regenerating Rat Liver ◽  
Bicarbonate Output

1. During the pre-replicative phase of the regenerating rat liver some interesting changes occur, which might selectively modify some mechanisms involved in bile formation, such as those responsible for the hypercholeretic effect of ursodeoxycholic acid. The aim of the present work was to gain information on this point. 2. Anaesthetized male Wistar rats (∼ 250 g) were used. The animals underwent two-thirds hepatectomy 1, 6 or 12 h before collection of bile samples was begun. Very early after hepatectomy (1 h) spontaneous bile flow and bile acid output were increased. Both returned to values not significantly different from those of the controls at 6 h. Bile flow increased again at the end of the pre-replicative phase. Taurocholate infusion (200 nmol min−1 g−1 calculated liver weight) induced increases in bile flow and bile acid output that were similar in both the control and hepatectomized rats, regardless of the time of the pre-replicative phase considered. 3. Cholic acid and ursodeoxycholic acid were infused (300 nmol min−1 g−1 calculated liver weight) into control and partially hepatectomized rats (at the mid-point of the pre-replicative phase, i.e. 6 h after surgical liver resection). Cholic acid-induced bile flow, bile acid and bicarbonate output expressed per g of remaining liver were similar in control and in hepatectomized rats. By contrast, ursodeoxycholic acid-induced choleresis was profoundly altered during the pre-replicative phase. As expressed per g of remaining liver, bile flow was markedly reduced (− 17%, P < 0.05), in spite of total bile acid output being greatly increased (+ 148%, P < 0.001). The reduced choleretic effect of ursodeoxycholic acid may be due to a lowered stimulation of bicarbonate secretion (− 41%, P < 0.01). 4. Factors known to reduce ursodeoxycholic acid-induced bicarbonate secretion into bile, such as decreased plasma bicarbonate concentrations and lowered total hepatic carbonic anhydrase activity, cannot account for the loss of the ability of ursodeoxycholic acid to stimulate bicarbonate secretion during the pre-replicative phase. However, the bile acid conjugation patterns were dramatically altered early after hepatectomy (6 h). In bile from the control animals the major ursodeoxycholic acid conjugation was with glycine, whereas in hepatectomized rats it was with taurine. 5. In summary, our results indicate that during the prereplicative phase of the regenerating rat liver, a loss occurs in the hypercholeretic effect of bile acids such as ursodeoxycholic acid. However, the choleretic effect of non-hypercholeretic bile acids such as cholic acid and taurocholic acid was not altered. Moreover, the existence of a relationship between the decrease in bile flow and bicarbonate output and the marked increase in the secretion of low-pKa conjugated bile acid derivatives is suggested.

Effects of selective zonal injury on bile acid-induced bile flow in the isolated rat liver

1993 ◽  
Vol 264 (6) ◽  
pp. G1103-G1111
Author(s):  
M. J. Monte ◽  
M. D. Badia ◽  
F. Palomero ◽  
M. Y. el-Mir ◽  
J. R. Alonso ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Flow ◽  
High Performance ◽  
Acid Output ◽  
High Performance Liquid Chromatographic ◽  
Histological Evaluation ◽  
Lactate Dehydrogenase Release ◽  
Significant Difference ◽  
Early Peak ◽  
Isolated Rat

The importance of acinar heterogeneity in ursodeoxycholic acid (UDCA)-induced bile flow was assessed in isolated rat livers that underwent restricted acinar damage by antegrade (A; 50 nmol) or retrograde (R; 500 nmol) digitonin infusion, as confirmed by histological evaluation. Stability of reduced (-40%) bile flow and perfusion flow (-25%) at constant pressure and potassium and lactate dehydrogenase release indicated similar viability of A and R preparations. They also showed similar abilities to secrete increasing doses of taurocholate (TC, maximal secretion rate approximately 105 nmol.min-1.g liver-1). TC-induced bile flow was not reduced by digitonin. In contrast, UDCA-induced choleresis was sensitive to zonal injury. Moreover, increases in bile flow and bicarbonate secretion observed under UDCA infusion (1.5 mumol/min) were lower in R than in A (-33 and -51%, respectively). No significant difference was observed in UDCA amidation or glucuronation between A and R preparations. With the use of single-pass perfusion on intact isolated livers that received 1 or 10 mumol UDCA, an early peak in bile acid output was observed to occur before the appearance of the major secretory peak. This was not found when 1 mumol of chenodeoxycholic acid bolus or trace amounts of [14C]TC were given. High-performance liquid chromatographic analysis of the early peak revealed it to be mainly due to unconjugated UDCA. This suggests the existence of a diffusional pathway for protonated bile acids and hence that the exist of lipophilic UDCA from bile during its way through the intra-acinar canaliculi across this pathway is also possible.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of bile acid structure on bile flow and biliary lipid secretion in the hamster

1984 ◽  
Vol 247 (6) ◽  
pp. G736-G748 ◽  
Author(s):  
D. Gurantz ◽  
A. F. Hofmann
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Bile Flow ◽  
Enterohepatic Circulation ◽  
Acid Output ◽  
Chain Structure ◽  
Side Chain ◽  
Biliary Lipid ◽  
Lipid Secretion ◽  
Acid Structure

A comprehensive study of the influence of bile acid structure on bile flow and biliary lipid secretion was carried out by infusing pure bile acids at a physiological rate into the proximal small intestine of a bile fistula hamster. Twelve individual bile acids, cholate (C), ursocholate (UC), chenodeoxycholate (CDC), and ursodeoxycholate (UDC) as their glycine (G), taurine (T), or unconjugated form, were studied so that influence of the hydroxy substituents as well as side-chain structure could be defined. The pattern of bile acid output was dependent on bile acid structure and reflected the site and rate of intestinal absorption. Conjugated bile acid output was delayed because of late ileal absorption, and TUC was poorly absorbed. Unconjugated trihydroxy bile acids, C and UC, also exhibited a delay in absorption, while CDC and UDC were absorbed immediately and achieved the highest bile acid output. Unconjugated bile acids were conjugated initially mostly with taurine and then mostly with glycine. The effect of glycine conjugates of each bile acid on bile flow and biliary lipid secretion was similar to that of their corresponding taurine conjugates. All conjugated bile acids induced a similar rate of bile flow (9–15 microliter bile/mumol bile acid), but unconjugated bile acids other than C induced more flow (20–25 microliter bile/mumol bile acid) than their corresponding conjugates. Conjugates of the dihydroxy bile acids induced a greater secretion of phospholipid and cholesterol than cholyl conjugates, whereas conjugates of UC were unique in inducing extremely low phospholipid and cholesterol secretion. For an increase of 1 mumol X min-1 X kg-1 in bile acid output, the increase in phospholipid secretion was 0.072 mumol X min X kg for GCDC and TCDC; 0.051 mumol X min-1 X kg-1 for GUDC and TUDC; and 0.030 mumol X min-1 X kg-1 for GC and TC. Increase in cholesterol output per mumol X min-1 X kg-1 of bile acid output was 0.013 mumol X min-1 X kg-1 for GCDC and TCDC, 0.011 mumol X min-1 X kg-1 for GUDC and TUDC, and 0.005 mumol X min-1 X kg-1 for GC and TC. In general, unconjugated bile acids induced more phospholipid and cholesterol than their corresponding conjugates; however, the rank-order effect of the steroid nucleus substituents was similar to that observed for the respective conjugates. These results indicate that both nuclear and side-chain structure influence the enterohepatic circulation and biliary secretory properties of bile acids.(ABSTRACT TRUNCATED AT 400 WORDS)

Permeation patterns of polar nonelectrolytes across the guinea pig biliary tree

1984 ◽  
Vol 247 (5) ◽  
pp. G527-G536 ◽  
Author(s):  
N. Tavoloni
Keyword(s):  
Steady State ◽  
Bile Acid ◽  
Bile Duct ◽  
Guinea Pig ◽  
Bile Acids ◽  
Bile Flow ◽  
Biliary Tree ◽  
Canalicular Membrane ◽  
Biliary Clearance ◽  
Spontaneous Secretion

The biliary permeation of polar nonelectrolytes was studied in anesthetized, bile duct-cannulated guinea pigs with functional cholecystectomy and nephrectomy. During spontaneous secretion, the steady-state bile-to-plasma ratio (B/P) of [14C]urea, [14C]erythritol, [14C]mannitol, [3H]sucrose, and [3H]inulin was 1.02, 0.90, 0.38, 0.12, and 0.04, respectively. Differently structured hydroxy bile acids, but not taurodehydrocholate, reversibly diminished [14C]erythritol and [14C]mannitol B/P during choleresis, and with some of them, particularly taurocholate and glycochenodeoxycholate, the biliary clearance of either solute declined below precholeretic levels. For any given hydroxy bile acid, the degree of B/P diminution was directly related to the molecular radii of these two inert carbohydrates. All bile acids failed to decrease [14C]urea, [3H]sucrose, and [3H]inulin B/P. On the contrary, most of them irreversibly increased [3H]sucrose and [3H]inulin permeability. These results suggest that in the guinea pig 1) hydroxy bile acids diminish the size or rearrange the architecture of the canalicular membrane "aqueous pores" through which [14C]erythritol and [14C]mannitol enter the canaliculus, and 2) solutes of the size of or smaller than [14C]mannitol enter bile primarily through a transcellular route, whereas [3H]sucrose, and [3H]inulin permeate mainly via a transjunctional shunt pathway. These studies indicate that [14C]erythritol and [14C]mannitol cannot be used to estimate canalicular bile flow in this species.

Bile secretion in rats with indomethacin-induced intestinal inflammation

1996 ◽  
Vol 270 (5) ◽  
pp. G804-G812 ◽  
Author(s):  
T. Yamada ◽  
M. Hoshino ◽  
T. Hayakawa ◽  
Y. Kamiya ◽  
H. Ohhara ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Salt ◽  
Bile Flow ◽  
Intestinal Inflammation ◽  
Acid Output ◽  
Bile Secretion ◽  
Pool Size ◽  
Secretory Function ◽  
Indomethacin Treatment

The objective of this study was to characterize the bile secretion, including the composition of biliary bile acids, bile salt pool size, and transcytotic vesicle transport, in a rat model of subacute intestinal inflammation induced by indomethacin. Indomethacin treatment significantly decreased bile acid-independent bile flow and biliary secretion of bile acid and cholesterol, while increasing biliary phospholipid output in vivo. Although indomethacin treatment did not change the bile salt pool size in vivo, alpha- and beta-muricholic acids were significantly deceased and hyodeoxycholic and deoxycholic acids were increased in bile. Bile flow and the transport maximum of taurocholate did not decrease, and biliary horseradish peroxidase output was significantly enhanced in isolated perfused livers from indomethacin-treated rats. Endotoxin in the portal blood was significantly increased in rats treated with indomethacin. Clindamycin slightly reduced intestinal inflammation but significantly prevented decreases in bile flow, bile acid output, and transport maximum of taurocholate. We conclude that, although biliary secretory function was apparently decreased in vivo, that of hepatocyte function was maintained in this model.

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