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At least 37 records · Page 2Linked to original sources

PubMed2000

Review article: the 'mechanical pumps' and the enterohepatic circulation of bile acids--defects in coeliac disease.

Bile acid pool size is maintained relatively constant at about 3-5 g in healthy subjects by two mechanisms, enterohepatic circulation and de novo synthesis of bile acids. This latter mechanism compensates for the daily faecal loss (about 0.2-0.6 g) of bile acids, whereas the bulk of the pool is conserved by the former mechanism. The driving forces of the enterohepatic circulation are constituted by chemical pumps, including intestinal absorption and hepatic uptake, and by mechanical pumps, including gall-bladder and intestinal motility. The latter provide the main propulsive forces for bile acids to reach the site of intestinal absorption, and by contrast with the very rapid chemical pumps, mechanical pumps have storage capacity for the bile acid pool and therefore comprise the slow limb of the enterohepatic circulation. In coeliac disease, a disease classically described as a malabsorption syndrome associated with mucosal atrophy of the small intestine, both gall-bladder and small intestinal motor functions are impaired, and in this article we review the mechanisms involved in these defects, how they influence the enterohepatic circulation of bile acids, and the evidence supporting the concept that both the gall-bladder and the small intestinal motor functions represent the main factors affecting the kinetics of the enterohepatic circulation.

Bile Acids and Salts↗

PubMed1997

Pharmacokinetic analysis of enterohepatic circulation of etodolac and effect of hepatic and renal injury on the pharmacokinetics.

This study was designed to evaluate the enterohepatic circulation of racemic etodolac in rats. Additionally, the effect of hepatic and renal failure on the pharmacokinetics was estimated. The biliary excretion and the reabsorption of the drug excreted in bile were examined in order to clarify the effect of enterohepatic circulation on the disposition, and a pharmacokinetics model was applied to describe the enterohepatic circulation. The relatively rapid elimination of etodolac was seen in the bile-exteriorized rats (BE rat) compared with that in control rats. Total biliary excretion of etodolac, mainly as glucuronides, after intravenous administration was about 45% of the dose, indicating extensive enterohepatic circulation of the drug. The plasma concentrations of the drug in bile duct-linked rats approximately agreed with the simulation curve by the model, with the peak concentration 6-7 h after dosing. The elimination of the drug was markedly retarded in rats with hepatic (CCI4-induced) and renal (uranyl acetate-induced) failure, and high plasma levels were maintained over the longer times, due to greatly decreased distribution volume. The biliary excretion of etodolac enantiomers was not significantly different between the control and CCI4-groups, suggesting that hepatic glucuronyl transferase activity was preserved in rats impaired by CCI4.

Acute Kidney Injury↗

PubMed2005

Absorption and enterohepatic circulation of baicalin in rats.

Pharmacokinetics of baicalin, in form of its parent drug (BG) and conjugated metabolites (BGM), were studied following intravenous and oral administration of baicalin to intact rats. The enterohepatic circulation of BG and BGM was also assessed in a linked-rat model. Multiple plasma and urine samples were collected, and concentrations of BG and BGM were determined using a liquid chromatography/tandem mass spectrometry method. The concentration of BGM was assayed in the form of baicalein after treatment with beta-glucuronidase/sulfatase. After i.v. administration, plasma concentration of BG rapidly declined with the elimination half-life (T1/2) of 0.1 till 4 h post dose, followed by slight increase from 4-8 h in plasma concentrations after drug administration. These plasma concentrations resulted in a significant prolongation of the terminal elimination half-life of BG (T1/2 TER, 9.7 h). BG also displayed slight increase in plasma concentrations (12-24 h) after oral administration, with T1/2 TER of 12.1 h. Based on the AUC of BG and BGM, the absolute bioavailability of baicalin was 2.2+/-0.2% and 27.8+/-5.6%, respectively. The exposure of baicalin to the systemic circulation was approximately 118-fold lower than that of BGM after oral administration (AUC0-t, 4.43 versus 523.97 nmol.h/mL). The high extent of glucuronidation suggested the possible presence of enterohepatic circulation, which was confirmed in the linked-rat model since plasma concentrations of BG and BGM were observed in bile-recipient rats at 4 to 36 h. The extent of enterohepatic circulation after intravenous administration of baicalin was 4.8% and 13.3% for BG and BGM, respectively. It was determined that 18.7% and 19.3% of the administered baicalin were subjected to enterohepatic circulation for BG and BGM, respectively, after oral administration. These results confirm that BG undergoes extensive first-pass glucuronidation and that enterohepatic circulation contributes significantly to the exposure of BG and BGM in rats.

Animals↗

PubMed1977

[Enterohepatic circulation of bile acids and biliary lipid secretion].

The enterohepatic circulation of bile acids in man is reviewed. The chemistry of biliary bile acids is summarized and related to the formation of primary bile acids in the liver and secondary bile acids in the intestinal lumen. New findings showing that lithocholic acid is absorbed in man are presented, and the recent experiments showing that lithocholic acid is extensively sulfated are reviewed. The consistent hepatotoxicity of chenodeoxycholic acid in the rhesus monkey, which contrasts with its non-toxicity in man, is explained by the inability of the rhesus monkey to sulfate abosrbed lithocholic acid; this accumulates in the enterohepatic circulation of the monkey causing liver damage. In man, absorbed lithocholic acid is rapidly sulfated, and the sulfated conjugates are excreted fecally without enterohepatic cycling. The physical chemistry of bile is highlighted, and it is shown that the saturation of bile with cholesterol depends on the amount of bile acids passing through the liver: at low bile acid flow rates, such as occurs during overnight fasting, bile is supersaturated in both gallstone and healthy persons. Chenodeoxycholic acid decreases cholesterol secretion into bile, renders bile unsaturated during most of the day and night, and thus induces gallstone dissolution.

Animals↗

PubMed1990

Factors affecting the enterohepatic circulation of oral contraceptive steroids.

Oral contraceptive steroids may undergo enterohepatic circulation, but it is relevant for only estrogens, because these compounds can be directly conjugated in the liver. Animal studies show convincing evidence of the importance of the enterohepatic circulation, but studies in humans are much less convincing. The importance of the route and the rate of metabolism of ethinyl estradiol are reviewed. Some antibiotics have been reported anecdotally to reduce the efficacy of oral contraceptive steroids, but controlled studies have not confirmed this observation. Although gut flora are altered by oral antibiotics, the blood levels of ethinyl estradiol are not reduced, and one antibiotic at least (cotrimoxazole) enhances the activity of ethinyl estradiol.

Anti-Bacterial Agents↗

PubMed1988

Enterohepatic circulation of NY-198, a new difluorinated quinolone, in rats.

Enterohepatic circulation of NY-198 in rats was studied. NY-198 glucuronide in the bile was rapidly hydrolyzed to NY-198 by the intestinal contents. Hydrolyzed and parent NY-198 in the bile were reabsorbed from the intestine. The amount of NY-198 in enterohepatic circulation was 59.8% of that excreted in the bile.

Animals↗

PubMed1977

Metabolism of steroid and amino acid moieties of conjugated bile acids in man. V. Equations for the perturbed enterohepatic circulation and their application.

Equations previously developed to describe the enterohepatic circulation of the major biliary bile acids in man (Gastroenterology 67:887, 1974) were modified in order to predict the effect on biliary bile acid composition and pattern of amino acid conjugation after prototypic perturbations of the enterohepatic circulation in man. For the steroid moiety, the effects of bile acid feeding, increased recycling frequency, decreased intestinal conservation, and increased dehydroxylation were simulated. For the glycine or taurine moiety, the effect of increased deconjugation or preferential loss of one of the amino acid moieties was simulated. For the steroid moiety, the steady state biliary bile acid composition reflects the balance between input and conservation for each bile acid. Similarly, the distribution of bile acids between glycine and taurine conjugates reflects the balance between conjugation and conservation for each amino acid moiety. Because these values may vary widely and independently, analysis of biliary bile acid composition in terms of the steroid moiety or the glycine-taurine ratio per se cannot be used to infer the relative rates of input or conjugation.

Amino Acids↗

PubMed1988

Rat enterohepatic circulation and intestinal distribution of enterally infused thyroid hormones.

The enterohepatic circulation (recycling), intestinal (gut) distribution, metabolism, and excretion of enterally infused thyroid hormones were studied in the intact rat under approximately normal physiological steady state conditions. Rats with 7-day osmotic minipumps implanted ip received constant intraduodenal infusions to steady state of very small trace doses of either 125I-labeled T3 (T3*) or T4 (T4*). Enterohepatic and other pathways remained open to normal function, and in particular, there was no biliary diversion or ligation. Complete feces and urine were collected daily, to assess daily distributions of radioactivity and establishment of the steady state, which occurred by day 3. On day 7, rats were anesthetized, blood was sampled, whole intestine and minipumps were removed, and the gut was separated into six segments. Fecal samples and the contents of each gut section were homogenized, ethanol extracted, evaporated, and reconstituted in NaOH for quantitative aqueous chromatography along with infusate, urine, and plasma samples, on Sephadex G-25 columns. No T3* or T4* was found in urine, but feces contained 39% of the T3* infused and 36% of the T4* infused in steady state. Statistically significant amounts of both T3* and T4* in systemic plasma on day 7 clearly indicated absorption of the hormones from the intestine, distinctly demonstrating an enterohepatic circulation of T3 and T4 under experimental conditions closely approximating the physiological steady state. This also establishes the intestine (with its contents) as an exchangeable hormone pool, physiologically internal to the system regulating thyroid hormones and their distribution. Gut contents contained 52 times more T3* and 4.34 times more T4* than corresponding plasma pools in steady state. Kinetic analysis of the data indicated that somewhat more than half of the T3* or T4* infused was absorbed from gut to liver (primary absorption), and up to 34% of the T3* infused and 43% of the T4* infused reached the systemic circulation (secondary absorption/bioavailability). Gut contents longitudinal distribution data 1) confirm existing evidence that thyroid hormone conjugates, formed elsewhere, exist in gut contents and are hydrolyzed there; 2) demonstrate that deconjugation becomes quantitatively significant, and thus may be initiated, at the level of the cecum; and 3) strongly suggest that absorption of unconjugated hormone occurs from at least the small intestine, all under normal physiological conditions.

Animals↗

PubMedDate not supplied

Enterohepatic circulation of T-2 toxin metabolites in the rat.

The enterohepatic circulation of T-2 toxin and its conjugated metabolites was examined in bile duct-cannulated male rats. Rats administered tritiated T-2 toxin intraduodenally (id) eliminated 44.65% and 57.25% of the administered dose in the bile within 4 and 8 hr post-dosing, respectively. TLC profiles of the T-2 metabolites were similar after intravascular and id administration. The major metabolites detected were 3'-OH-hydroxytryptamine-2 (HT-2), glucuronic acid conjugates, T-2 tetraol (TOL), 4-deacetylneosolaniol (4-DN), and HT-2. Tritium-labeled glucuronides obtained from the bile of rats administered [3H]T-2 toxin intravascularly were extracted and purified using C-18 and silica column chromatography. Enzymatic hydrolysis followed by TLC and GC/MS indicated that the aglycone portion of the glucuronides were composed of 3'-OH HT-2, HT-2, 4-DN, and TOL. After id administration of the glucuronides the rats eliminated 6.01% (4 hr) and 11.86% (8 hr) of the dose in the bile. No free metabolites of T-2 toxin were detected in the bile of any animals administered the purified glucuronides. Oral treatment of the rats with the beta-glucuronidase inhibitor, saccharolactone, did not produce a significant decline in the amount of radioactivity recovered in the bile following administration of the tritium-labeled glucuronides. These studies substantiate the enterohepatic circulation of T-2 toxin metabolites.

Animals↗

PubMed1995

Reduction of bovine plasma cholesterol concentration by partial interruption of enterohepatic circulation of bile salts: a novel hypocholesterolemic model.

Interruption of enterohepatic circulation (EHC) of bile salts in several species is known to cause a significant decrease in plasma concentrations of low density lipoprotein (LDL) cholesterol, but to have little effect on high density lipoprotein (HDL) cholesterol. The present study, for the first time, demonstrates that partial interruption of EHC dramatically reduces both plasma LDL and HDL cholesterol concentrations in cattle. Five adult Holstein cows were surgically altered to allow controlled portions of bile flow to be diverted from the body. The animals were fed a low-fat, cholesterol-free diet. In two experiments, bile was diverted at 50% and 22% of total flow rates. By day 8 of diversion, both rates reduced mean plasma cholesterol from baseline (85 mg/dl) to about 8 and 18 mg/dl, respectively. Cholesterol was reduced in equal proportions in all lipoprotein fractions. In addition, plasma concentrations of triglycerides and phospholipids were also dramatically reduced. All of these plasma lipids returned to baseline within 1 week after restoration of bile flow. To determine the hepatic response to bile diversion, liver cholesterol concentrations, cholesterol synthesis rates, and LDL receptor-binding activities were determined in biopsy samples. In response to bile diversion, hepatic cholesteryl esters were markedly depleted while hepatic cholesterol synthesis rates were increased by more than 10-fold. Nevertheless, because the basal cholesterol synthesis rate was so low, it was estimated that the increase in synthesis would have supplied no more than 5% of the sterols depleted during bile diversion (1.2 vs. 25 mmol/day). LDL receptor-binding activity was significantly elevated, suggesting an increased uptake of plasma lipoprotein cholesterol by the liver. These results suggest that the unique sensitivity of bovine plasma cholesterol to enterohepatic circulation interruption might occur as a result of the inherently low rate of hepatic cholesterol synthesis in cattle. This hypocholesterolemic model might serve as an interesting tool for the study of factors regulating plasma HDL cholesterol.

Animals↗

PubMed1980

[The enterohepatic circulation of estradiol and ethinylestradiol in the rat].

After intraduodenal administration of 6,7-3H-estradiol to rats about 56% of the radioactive dose is excreted in the bile within 4.5 h. The bulk of this radioactivity is confined to glucuronide conjugates. By using different methods it is shown that 12-16% of the administered estradiol dose is excreted in bile as glucuronides of estrone and estradiol. Similarly, after i.v. administration of 6,7-3H-ethinylestradiol 12% of this dose appears in bile of rats as ethinylestradiolgucuronide. Thes conjugates of the biologically active estrogens (estrone, estradiol, ethinylestradiol), upon removal of the glucuronic acid moiety by action of gut bacterial enzymes, may make available the active estrogenic compounds to the enterohepatic circulation. Therefore, enterohepatic circulation of estrogens may be of some biological importance in the rat.

Animals↗

PubMedDate not supplied

Chemistry and enterohepatic circulation of bile acids.

A brief review is given of the chemistry of bile acids, emphasizing the relationship between chemical structure, physical properties and enterohepatic cycling of the major primary and secondary bile acids. Features of the enterohepatic circulation of primary and secondary bile acids in man are summarized. The effects of bile acid feeding on the composition of the enterohepatic circulation in man are reviewed. Methods for characterizing the enterohepatic circulation of bile acids in man are tabulated.

Animals↗

PubMed1976

The effect of diether phosphatidylcholine on the enterohepatic circulation of biliary sterols.

The effect of diether phosphatidylcholine on the enterohepatic circulation of bile salts and cholesterol was determined using the bile duct cannulated rat. Animals were infused intraduodenally with a solution containing radioactive bile salts and cholesterol. Phospholipid was also present in the infusate. In control animals it was supplied by pig liver phosphatidylcholine (diester). For experiments, equimolar amounts of diether phosphatidylcholine were used. No difference was observed between control and experimental groups for absorption and subsequent secretion of bile salts into bile. Significantly less cholesterol was absorbed, however, by experimental rats. This was correlated with a decreased secretion of radioactive cholesterol into bile. In controls, almost 14% of the administered dose of cholesterol appeared in bile over the period of infusion while the value for experimentals was 5%. It is concluded that diether phosphatidylcholine inhibits the enterohepatic circulation of cholesterol but not of bile salts.

Animals↗

PubMed1983

The enterohepatic circulation of bile acids during continuous liquid formula perfusion of the duodenum.

The enterohepatic circulation of bile acids was studied in 16 normal volunteers and 8 cholecystectomy patients during continuous liquid formula perfusion of the duodenum. The fasting bile acid pool size in the 16 normals (5.534 +/- 1.472 mmol) exceeded the circulating pool size (3.643 +/- 1.126 mmol) by 33.4% +/- 13.4. The difference between fasting and circulating pool sizes was significantly and inversely related to the percentage of the fasting pool that was emptied in the duodenum during the first perfusion hour (r = -0.76; P < 0.001). No relation was found between the circulating bile acid pool size and the calculated rate of recycling of the pool, but a strong relation was found between the cycling pool and the basal hourly bile acid outputs (2.08 +/- 0.77 mmol/hr) in the duodenum (r = 0.82; P < 0.001). In cholecystectomy patients the circulating pool size (3.30 +/- 1.39 mmol) and the basal bile acid output (1.65 +/- 0.98 mmol/hr) were slightly lower than in the normal volunteers. The bile acid pool size was not related to the cycling rate and there was a strong relation between pool size and bile acid secretion (r = 0.85; P < 0.001). As the fasting pool, measured using the method of Duane et al. (1975. J. Lipid Res. 16: 155-158), is probably overestimated by +/-14%, the remaining difference of +/-19% with the pool circulating during formula perfusion might be caused by incomplete gallbladder emptying. In these experimental conditions basal bile acid outputs reflect closely the size of the circulating bile acid pool in normals as well as in cholecystectomy patients.-Rutgeerts, P., Y. Ghoos, and G. Vantrappen. The enterohepatic circulation of bile acids during continuous liquid formula perfusion of the duodenum.

Adult↗

PubMed1988

Evidence for an enterohepatic circulation of ochratoxin A in mice.

The distribution and elimination of [3H]ochratoxin A (OTA) from stomach content and tissue, intestine content and tissue, liver, bile, serum and urine of Swiss male mice which had received a single low dose of OTA by intubation was followed as a function of time. The profiles of radioactivity do not show a smooth decline after the absorption period, but an oscillating pattern with rapid declines followed by increases which favour the assumption of an enterohepatic circulation. Between 28% and 68% of conjugated OTA together with OTA cleavage products were found in bile giving evidence for biliary excretion of OTA and its metabolites in mice. When given i.m. to mice [3H]OTA is already found after 30 min in bile and intestine contents and its elimination patterns show several peaks confirming the biliary excretion and the enterohepatic circulation. Cholestyramine, which is known to prevent the enterohepatic circulation of drugs and toxins, changes the profile of elimination of OTA which no longer presents the cyclic pattern. This result is also in favour of an enterohepatic circulation of OTA. When phenylalanine is given together with OTA by oral gavage the toxicokinetics of the mycotoxin change completely in the different body fluids, in stomach and intestine content and tissues. Phenylalanine seems to facilitate the gastric absorption of OTA and the gastro-intestinal transit. It increases also its early excretion into urine and bile. However, its elimination pattern no longer shows the oscillating pattern. Thus phenylalanine seems to inhibit the intestinal reabsorption of OTA conjugates.

Animals↗

PubMed1987

The enterohepatic circulation of methotrexate in vivo: inhibition by bile salt.

We examined the enterohepatic circulation of methotrexate (MTX) in the rat in vivo and determined the effect of the unconjugated bile salt, cholate, on the process. MTX (70 mg/kg body weight) was administered i. v. and the bile salt (1 mM) was delivered through intestinal perfusion. In the control group 38.43% +/- 4% of the administered dose of MTX appeared in bile 2 h after administration of the drug. In the bile salt-treated group 21.4% +/- 3.7% of the administered doses of MTX appeared in bile, which was significantly lower (P less than 0.01) than the proportion in the control group. The liver content of MTX was depressed by 23% in the bile salt-treated group compared with the control group. This study demonstrates, in vivo, the important role that the enterohepatic circulation plays in exposing the small intestine to toxic levels of MTX and shows that the unconjugated bile salt, cholate, inhibits the process.

Animals↗

PubMed1984

Effects of sphincterectomy on bile acid enterohepatic circulation in dogs.

Relative rates of bile enterohepatic circulation (EHC) and bile acid pool distribution were compared in intact and sphincterectomized dogs with portacaval shunt. There was no significant difference in the rates of EHC or in the bile acid pool distribution in the groups of animals. Feeding and cholecystokinin administration caused similar increases in bile acid EHC rates in sphincterectomized and intact animals. It was concluded that the sphincter of Oddi has little or no effect on these aspects of bile acid metabolism in dogs.

Ampulla of Vater↗

PubMed1993

Adaptive changes of hepatic bile salt transport in a model of reversible interruption of the enterohepatic circulation in the rat.

The reversibility and time course of the adaptive changes in hepatic bile salt transport related to modifications of the bile salt enterohepatic circulation and bile salt pool size have not been previously studied. For this reason a model of reversible interruption of entero-hepatic circulation was characterized in unrestrained rats, which allowed the study of changes in hepatic bile salt transport following bile salt pool depletion and subsequent restoration by either the de novo synthesis of bile acids or i.v. administration of exogenous taurocholate. Rats subjected to biliary drainage for 24 h through a transduodenal common bile duct cannula, followed by removal of the cannula and restoration of the enterohepatic circulation were studied at 24, 48 and 72 h. Neither light and electron microscopy examination nor plasma biochemical parameters showed evidence of necrosis, fibrosis, cholestasis or inflammatory changes. Maximum taurocholate secretory rate decreased to 50% following 24-h bile salt depletion. After restoration of the enterohepatic circulation maximum taurocholate secretory rate progressively increased to normal values at 72 h, following the normalization of the bile salt pool size, which had a similar composition compared with controls. The same effect was obtained when the native bile salt pool was substituted with exogenous taurocholate. Thus, adaptive down-regulation of hepatic bile salt transport capacity is a reversible process, related to restoration of entero-hepatic circulation and normalization of bile salt pool size.

Adaptation, Physiological↗