Intestinal absorption of bile acids in the rabbit: Different transport rates in jejunum and ileum

Aldini, Rita; Montagnani, Marco; Roda, Aldo; Hrelia, Silvana; Pl, Biagi; Roda, Enrico

doi:10.1053/gast.1996.v110.pm8566593

Cited by 69 publications

(54 citation statements)

References 3 publications

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“…27 Finally, we observed that the uptake of bile acids by human fibroblasts was more a function of bile acid polarity, i.e., number of hydroxyl groups, than of absolute hydrophobicity. These findings are supported by those of Van Dyke et al 12 and Aldini et al 47 for the nonsaturable, sodium-independent uptake of bile acids in the liver and intestine, respectively. The significance of the present studies in cultured fibroblasts lies in the correlation of the rate of bile acid uptake, i.e., diffusion, with the relative cytotoxicity in a cell which does not possess either a bile acid transporter or an efficient system for binding, and/or detoxifying these compounds.…”

Section: Discussionsupporting

confidence: 78%

Extrahepatic deposition and cytotoxicity of lithocholic acid: Studies in two hamster models of hepatic failure and in cultured human fibroblasts

et al. 1998

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Effects of bile acids on tissues outside of the enterohepatic circulation may be of major pathophysiological significance under conditions of elevated serum bile acid concentrations, such as in hepatobiliary disease. Two hamster models of hepatic failure, namely functional hepatectomy (HepX), and 2-day bile duct ligation (BDL), as well as cultured human fibroblasts, were used to study the comparative tissue uptake, distribution, and cytotoxicity of lithocholic acid (LCA) in relation to various experimental conditions, such as binding of LCA to low-density lipoprotein (LDL) or albumin as protein carriers. Fifteen minutes after iv infusion of [24-14 C]LCA, the majority of LCA in shamoperated control animals was recovered in liver, bile, and small intestine. After hepatectomy, a significant increase in LCA was found in blood, muscle, heart, brain, adrenals, and thymus. In bile duct-ligated animals, significantly more LCA was associated with blood and skin, and a greater than twofold increase in LCA was observed in the colon. In the hepatectomized model, the administration of LCA bound to LDL resulted in a significantly higher uptake in the kidneys and skin.

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Section: Discussionsupporting

confidence: 78%

Extrahepatic deposition and cytotoxicity of lithocholic acid: Studies in two hamster models of hepatic failure and in cultured human fibroblasts

et al. 1998

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“…The bile acid molecule is too large to pass paracellularly through the tight junctions of the intestinal epithelium and must be absorbed by transcellular passive or active mechanisms ( 34 ). Passive absorption of protonated uncharged bile acid species, unconjugated bile acids, and a small fraction of the glycine conjugates occurs down the length of the intestine ( 35 ). However, as most of the bile acid pool is conjugated to taurine or glycine and ionized, their uptake across the apical brush border membrane requires the presence of a transporter, and active carrier-mediated absorption of bile acids is restricted to the ileum ( 36,37 ).…”

Section: Physiology and Molecular Mechanisms Of Intestinal Bile Acid mentioning

confidence: 99%

“…The general consensus from numerous studies is that ileal active transport is the major route for conjugated bile acid uptake, whereas the passive or facilitative absorption present along the length of the small intestine may be signifi cant for unconjugated and some glycine-conjugated bile acids ( 34,35,(40)(41)(42). Although bile acids in most vertebrates are conjugated to taurine, the bile acid pool of humans includes a signifi cant proportion of glycine conjugates ( 43,44 ).…”

Section: Intestinal Apical Brush Border Membrane Transportmentioning

confidence: 99%

Intestinal transport and metabolism of bile acids

Dawson

Karpen

2015

Journal of Lipid Research

424

371

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“…Undoubtedly, heterogeneity of absorptive carriers would bring about variations in absorption. Regional or segmental distribution of apical transporters-the oligopeptide transporter, PEPT1 (Fei et al, 1994), the apical bile salt transporter (Shneider et al, 1995;Aldini et al, 1996), the organic anion transporting polypeptide 3 (Walters et al, 2000), the monocarboxylic acid transporter 1 (Tamai et al, 1999;Cong et al, 2001), and the nucleoside transporter (Ngo et al, 2001)-is well recognized. Heterogeneity is further known to exist for both metabolic enzymes and efflux transporters.…”

mentioning

confidence: 99%

Segmental Intestinal Transporters and Metabolic Enzymes on Intestinal Drug Absorption

Tam¹,

Tirona²,

Pang³

2003

Drug Metab Dispos

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This article is available online at http://dmd.aspetjournals.org ABSTRACT:Recently, a physiologically-based, segregated flow model that incorporates separate intestinal tissue and flow to both a nonabsorptive and an absorptive outermost layer (enterocytes) was shown to better describe the observations on route-dependent morphine glucuronidation in the rat small intestine than a traditional physiologically-based model. These theoretical models were expanded, as the segmental segregated flow model and the segmental traditional model, to view the intestine as three segments of equal lengths receiving equal flows to accommodate heterogeneities in segmental transporter and metabolic functions. The influence of heterogeneity in absorptive, exsorptive, and metabolic functions on drug clearance, bioavailability (F), and metabolite formation after intravenous and oral dosing was examined for the intestine when the tissue was the only organ of removal. Simulations were performed for first-order conditions, when drug partitioned readily (flow-limited distribution) or less readily (membrane-limited distribution) into intestinal tissue, and for different gastrointestinal transit times. The intestinal clearance was found to be inversely related to the rate constant for absorption of a drug that was subjected to secretion and was positively correlated with the metabolic and secretory intrinsic clearances. F was positively correlated with the absorption rate constant but was inversely related to the metabolic and secretory intrinsic clearances. The gastrointestinal transit time decreased metabolite formation, increased clearance, and decreased F. The simulations further showed that a descending metabolic intrinsic clearance yielded a lower F and an ascending segmental distribution of metabolic intrinsic clearance yielded a higher F.The small intestine is endowed with transporters that effect the penetration of drugs across the luminal (or apical) membrane into the cell against a concentration gradient (for review, see Tsuji and Tamai, 1996;Lin et al., 1999). Permeation via passive diffusion of lipophilic drugs exists and is highly correlated to the surface area of contact and the pKa that influence the degree of ionization and hence lipophilicity. The varying abundance of the villi along the intestinal length constitutes differing surface areas among the intestinal segments, being highest at the duodenum and upper jejunum and lowest toward the ileum (Magee and Dalley, 1986). Net apical to basolateral transport is additionally influenced by the presence of drug binding, metabolizing enzymes, transporters for efflux and basolateral transport, and the gastrointestinal motility that modulates drug transit time.Several models have been developed to describe processes of intestinal absorption, metabolism, and secretion simultaneously (Yu and Amidon, 1998;Ito et al., 1999;Cong et al., 2000). A traditional, physiologically-based model (TM 2 ), which regards the intestine as a single homogeneous compartment with all of the intestinal bl...

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Intestinal absorption of bile acids in the rabbit: Different transport rates in jejunum and ileum

Cited by 69 publications

References 3 publications

Extrahepatic deposition and cytotoxicity of lithocholic acid: Studies in two hamster models of hepatic failure and in cultured human fibroblasts

Extrahepatic deposition and cytotoxicity of lithocholic acid: Studies in two hamster models of hepatic failure and in cultured human fibroblasts

Intestinal transport and metabolism of bile acids

Segmental Intestinal Transporters and Metabolic Enzymes on Intestinal Drug Absorption

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