Estimation of bile acid excretion in man: comparison of isotopic turnover and fecal excretion methods

Subbiah, M.T.R.; Tyler, Nancy E.; Buscaglia, Marianne; Marai, L.

doi:10.1016/s0022-2275(20)37020-6

Cited by 52 publications

(3 citation statements)

References 22 publications

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“…Lithocholic acid (3R-hydroxy-5β-cholanoic acid; LC; I), deoxycholic acid (3R,12R-dihydroxy-5β-cholanoic acid; DOC; II), chenodeoxycholic acid (3R,7R-dihydroxy-5β-cholanoic acid; CDOC; III), cholic acid (3R,7R,12R-trihydroxy-5β-cholanoic acid; C; IV), hyodeoxycholic acid (3R,6R-dihydroxy-5β-cholanoic acid; HDOC; V), and ursodeoxycholic acid (3R,7β-dihydroxy-5βcholanoic acid; UDOC; VI) are the major C 24 acids (see Figure 1). DOC (II) and LC (I) are the major secondary bile acids found in the feces of humans (and some other animals) with healthy individuals excreting about 140 mg of DOC (II) and 90 mg of LC (I) acid per day (31). In this paper, we explore the potential of bile acids as a new class of pollution indicator.…”

Section: Introductionmentioning

confidence: 99%

“…The survival of bile acids and 5β-stanols in ancient soils and sediments is not surprising since they are the main excretory products of body cholesterol ( 15, 28−30 ) and possess structures that are conducive to their survival. Normal human feces contains more than 20 different bile acids that are formed from the primary bile acids, cholic and chenodeoxycholic acid ( − ). Two series of bile acids are found in nature, i.e., those containing 24 carbon atoms and those containing 27 or 28 carbon atoms.…”

Section: Introductionmentioning

confidence: 99%

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Bile Acids as a New Class of Sewage Pollution Indicator

Elhmmali

Roberts

Evershed

1997

Environ. Sci. Technol.

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The bile acid content of raw sewage, treated effluent, and estuarine sediment was determined as the first step in the development of bile acids as a new class of sewage pollution indicator. Sediments and particulates from raw sewage and effluent, were solvent extracted, saponified, fractionated by solid phase extraction (SPE) and "flash" column chromatography, derivatized, and analyzed by gas chromatography (GC) and GC/mass spectrometry (GC/ MS). Mass spectral comparisons confirmed unambiguously the presence of bile acids in all the samples studied. The major compounds detected were deoxycholic and lithocholic acids, together with minor components, in a characteristic distribution that reflected the predominantly human origin of the effluent. Bile acids were found to exist in a "bound" form and were released upon saponification. They were found to be quantitatively relatively more resistant to degradation during sewage treatment as compared to coprostanol. Some changes were observed in the abundances of certain minor bile acids, for example, the 3βepimers were much reduced in relative abundance in the treated effluent and sediment as compared to their 3R counterparts. Bile acids offer considerable promise as indicators of specific sources of sewage pollution, particularly if used in conjunction with the widely employed 5β-stanols, e.g., coprostanol.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Bile Acids as a New Class of Sewage Pollution Indicator

Elhmmali

Roberts

Evershed

1997

Environ. Sci. Technol.

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“…In both blood and liver, the CDCA species and bulk BA species represented the large majority of all measured BAs; lithocholic acid (LCA) species, although the most hepatotoxic, only represented a minor fraction in these two matrices, consistent with the literature. Furthermore, the model reasonably recapitulated: 1) total BA pool (simulated: ∼2.6 g, observed: 1.2–6.6 g), 2) BA synthesis rate (simulated: ∼440 mg/day, observed: 175–1,250 mg/day), 3) BA pool that is lost (and replaced) on a daily basis (simulated: ∼16%, observed: ∼5–35%), 4) large majority of BA pool residing in the gut (simulated: ∼78%, observed: ∼90%), and 5) a small fraction of lost BAs being eliminated via urine (simulated: ∼0.6%, observed: <1%) ( Subbiah et al, 1976 ; Mok et al, 1977 ; Vantrappen et al, 1981 ; Kullak-Ublick et al, 1995 ; Hofmann, 1999 ; Meier and Stieger, 2002 ). Additionally, the large majority of biliary BAs consists of CDCA species (simulated: ∼41%, observed: ∼35%) while only a minority consists of LCA species (simulated: ∼1%, observed: ∼1%); in contrast, due to gut bacteria-mediated BA metabolism, the large majority of fecal BAs consists of LCA species (simulated: ∼48%, observed: 32%), whereas only a minority consists of CDCA species (simulated: 2%, observed: 2%) ( Baars et al, 2015 ), which is reasonably captured by the model.…”

Section: Resultsmentioning

confidence: 99%

Investigating bile acid-mediated cholestatic drug-induced liver injury using a mechanistic model of multidrug resistance protein 3 (MDR3) inhibition

et al. 2023

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Inhibition of the canalicular phospholipid floppase multidrug resistance protein 3 (MDR3) has been implicated in cholestatic drug-induced liver injury (DILI), which is clinically characterized by disrupted bile flow and damage to the biliary epithelium. Reduction in phospholipid excretion, as a consequence of MDR3 inhibition, decreases the formation of mixed micelles consisting of bile acids and phospholipids in the bile duct, resulting in a surplus of free bile acids that can damage the bile duct epithelial cells, i.e., cholangiocytes. Cholangiocytes may compensate for biliary increases in bile acid monomers via the cholehepatic shunt pathway or bicarbonate secretion, thereby influencing viability or progression to toxicity. To address the unmet need to predict drug-induced bile duct injury in humans, DILIsym, a quantitative systems toxicology model of DILI, was extended by representing key features of the bile duct, cholangiocyte functionality, bile acid and phospholipid disposition, and cholestatic hepatotoxicity. A virtual, healthy representative subject and population (n = 285) were calibrated and validated utilizing a variety of clinical data. Sensitivity analyses were performed for 1) the cholehepatic shunt pathway, 2) biliary bicarbonate concentrations and 3) modes of MDR3 inhibition. Simulations showed that an increase in shunting may decrease the biliary bile acid burden, but raise the hepatocellular concentrations of bile acids. Elevating the biliary concentration of bicarbonate may decrease bile acid shunting, but increase bile flow rate. In contrast to competitive inhibition, simulations demonstrated that non-competitive and mixed inhibition of MDR3 had a profound impact on phospholipid efflux, elevations in the biliary bile acid-to-phospholipid ratio, cholangiocyte toxicity, and adaptation pathways. The model with its extended bile acid homeostasis representation was furthermore able to predict DILI liability for compounds with previously studied interactions with bile acid transport. The cholestatic liver injury submodel in DILIsym accounts for several processes pertinent to bile duct viability and toxicity and hence, is useful for predictions of MDR3 inhibition-mediated cholestatic DILI in humans.

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