Disease relevance of Enterohepatic Circulation

• Primary bile acid malabsorption (PBAM) is an idiopathic intestinal disorder associated with congenital diarrhea, steatorrhea, interruption of the enterohepatic circulation of bile acids, and reduced plasma cholesterol levels [1].
• In cholestasis the primary bile acid derivatives cholic and chenodeoxycholic acid glucosides amounted to 90%, whereas the trihydroxy bile acid glucoside had decreased to 5% of total bile acid glucoside excretion, indicating its alteration during enterohepatic circulation [2].
• To characterize further the role of bile acids in regulation of bile acid synthesis, we have administered pure taurine or glycine conjugates of ursodeoxycholic acid or cholic acid to chronic bile fistula rats by continuous intraduodenal infusion, thus simulating restoration of the enterohepatic circulation [3].
• Neonatal jaundice is principally the result of a transient deficiency of bilirubin conjugation, of a partial deficiency of hepatic bilirubin uptake and intracellular transport and of an increased enterohepatic circulation of the pigment [4].
• (4) Arylamine N-glucuronides were found to be susceptible to hydrolysis by E. coli beta-glucuronidase suggesting the release of carcinogenic arylamines in the gut and their enterohepatic circulation [5].

High impact information on Enterohepatic Circulation

• Enterohepatic circulation and microbial metabolism in the intestine were necessary for production of the methylsulfonyl-containing and other metabolites of propachlor in the conventional rat [6].
• Absence of changes in serum progesterone and gonadotropins during the dietary intervention is consistent with altered enterohepatic circulation of estrogens rather than with effects on the pituitary-ovarian axis [7].
• Description and simulation of a physiological pharmacokinetic model for the metabolism and enterohepatic circulation of bile acids in man. Cholic acid in healthy man [8].
• Bile acids, cholesterol, gallstone calcification, and the enterohepatic circulation of bilirubin [9].
• METHODS: Hepatocanalicular conjugate export pump-deficient (TR-) rats were used to selectively block diclofenac enterohepatic circulation without interrupting bile flow [10].

Chemical compound and disease context of Enterohepatic Circulation

• In view of the increased enterohepatic circulation of thyroxine (T4) and triiodothyronine (T3) in thyrotoxicosis, we proposed that cholestyramine, an anion exchange resin which binds iodothyronines, when used adjunctively with thionamides and a beta-blocker, would lower serum iodothyronine levels faster than would standard therapy alone [11].
• In spite of the known interference of CsA with the enterohepatic circulation of bile acids, in the majority of patients after orthotopic liver transplantation without cholestasis, graft dysfunction of rejection, treatment with CsA does not disturb kinetics of primary bile acids [12].
• In addition, colestimide was found to have high adsorption capacity for methotrexate, not only in water but also in media containing various physiological anions, and thus it is suggested that colestimide is a potential oral antidote to reduce possible toxicity by methotrexate through interruption of enterohepatic circulation [13].
• No evidence of enterohepatic circulation of doxorubicin in a patient with transitory biliary obstruction due to lymphoblastic lymphoma [14].
• The enterohepatic circulation of thyroxine (T4) and triiodothyronine (T3) is higher in thyrotoxicosis [15].

Biological context of Enterohepatic Circulation

• Intestinal absorption and enterohepatic circulation of N-formyl-methionyl-leucyl-125I-tyrosine, a bioactive synthetic analog of the bacterial chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine has been investigated in the rat [16].
• The enterohepatic circulation is essential for the maintenance of bile acids and cholesterol homeostasis [17].
• We evaluated the physiological consequences of FXR deficiency on bile formation and on the kinetics of the enterohepatic circulation of cholate, the major bile salt species in mice [18].
• We hypothesized that MRP3 might play a role in the enterohepatic circulation of bile salts by transporting them from enterocytes into circulating blood through the up-regulation of MRP3 expression, so we investigated the transcriptional control of MRP3 in response to bile salts [17].
• Here the effects on choleresis of its taurine conjugate tauroursodesoxycholate (TUDC), which is present in the enterohepatic circulation, were correlated with the activation of important elements of intracellular signal transduction in cultured rat hepatocytes and perfused rat liver [19].

Anatomical context of Enterohepatic Circulation

• Gallbladder hypomotility is considered a pathogenic factor for gallstone formation, providing the residence time for cholesterol crystal nucleation, but any effect on the enterohepatic circulation of bile acids and subsequently on biliary lipid composition is unknown [20].
• We conclude that Mrp3 functions as an alternative route for the export of bile acids and glucuronides from cholestatic hepatocytes, that the pump does not play a major role in the enterohepatic circulation of bile acids and that the lack of chemosensitivity is probably attributable to functional redundancy with other pumps [21].
• As bile diversion leads to changes in cholesterol metabolism, rats were equipped with permanent catheters in the bile duct and duodenum, allowing sampling of small amounts of bile from an intact enterohepatic circulation [22].
• Furthermore, it appears that the regulation of sterol synthesis in the intestinal mucosa, via HMG-CoA reductase, involves a complex interplay of the effects exerted by the level of alimentation, the enterohepatic circulation of bile, and the levels of plasma lipoproteins [23].
• Mammalian lignans are absorbed by passive diffusion from the large intestine and a substantial fraction of the absorbed mammalian lignans undergoes enterohepatic circulation, resulting in low diurnal variation in plasma levels of enterolactone [24].

Associations of Enterohepatic Circulation with chemical compounds

• The enterohepatic circulation of biliary lipids was maintained constant by infusion of a bile salt, lecithin, cholesterol replacement solution [25].
• Accumulation of bilirubin in the intestine during fasting allows enhanced enterohepatic circulation and results in an increased reflux to plasma [26].
• In fasting subjects with an intact bile acid enterohepatic circulation, per cent taurine-conjugated bile acids in bile was the same as per cent taurine conjugation of bile acids by the liver [27].
• The metabolism and enterohepatic circulation of deoxycholic acid (DCA), a major secondary bile acid in humans, was simulated using a linear multicompartmental physiologic pharmacokinetic model [28].
• Metabolism of steroid and amino acid moieties of conjugated bile acids in man. V. Equations for the perturbed enterohepatic circulation and their application [29].

Gene context of Enterohepatic Circulation

• NTCP and the ileal transporter ASBT (apical sodium-dependent bile acid transporter) are two sodium-dependent transporters critical for the enterohepatic circulation of bile acids [30].
• The gastrointestinal safety profile of this nonacidic, dual COX inhibitor that does not undergo enterohepatic circulation has been evaluated in extensive clinical trials [31].
• Of these, the ileal sodium bile acid transporter (isbt) and the hepatic sodium bile acid cotransporting polypeptide (ntcp) may be most important in determining the efficiency of bile acid recovery within the enterohepatic circulation [32].
• Our results indicate that alpha-T undergoes enterohepatic circulation and that the biliary secretion of alpha-T, basally and following chemical treatment, is dependent on the presence of a functioning mdr2 Pgp in rats and mice [33].
• Bile acids returning to the liver through the enterohepatic circulation down-regulate CYP7A1 transcription via the bile acid sensors farnesoid X receptor and HNF-4alpha [34].

Analytical, diagnostic and therapeutic context of Enterohepatic Circulation

• Radioactive lithocholate was administered intravenously to female rhesus monkeys with an exteriorized enterohepatic circulation, and the chemical form of biliary radioactivity was defined by thin layer chromatography [35].
• METHODS: We measured quantitatively the secretion of bile acids, phospholipids and cholesterol using the duodenal perfusion method, which allows assessment of biliary secretion without interruption of the enterohepatic circulation [36].
• The effects of fasting and feeding of a high-carbohydrate, low-fat diet on the glucuronidation and enterohepatic circulation (EHC) of lorazepam were examined in seven healthy men (age 18-30 years) and seven matched patients with Gilbert's syndrome [37].
• In our animal experiments the hypothesis was tested that a high-fiber (HF) diet reduces tumor promotion by interruption of the enterohepatic circulation resulting in lowered estrogen exposure of the estrogen-sensitive tissue [38].
• The enterohepatic circulation and metabolism of ethynodiol diacetate (3beta,17beta-diacetoxy-17alpha-ethynyl-estr-4-ene) in baboons were studied following the intravenous injection of this contraceptive steroid labeled with 14C (4-position) and with 3H (in either the 3- or 17-acetoxy moieties) [39].

References