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Publication Detail

Title: Endogenous bile acid disposition in rat and human sandwich-cultured hepatocytes.

Authors: Marion, Tracy L; Perry, Cassandra H; St Claire 3rd, Robert L; Brouwer, Kim L R

Published In Toxicol Appl Pharmacol, (2012 May 15)

Abstract: Sandwich-cultured hepatocytes (SCH) are used commonly to investigate hepatic transport protein-mediated uptake and biliary excretion of substrates. However, little is known about the disposition of endogenous bile acids (BAs) in SCH. In this study, four endogenous conjugated BAs common to rats and humans [taurocholic acid (TCA), glycocholic acid (GCA), taurochenodeoxycholic acid (TCDCA), and glycochenodeoxycholic acid (GCDCA)], as well as two BA species specific to rodents (ýý- and ýý-tauromuricholic acid; ýý/ýý TMCA), were profiled in primary rat and human SCH. Using B-CLEARýý technology, BAs were measured in cells+bile canaliculi, cells, and medium of SCH by LC-MS/MS. Results indicated that, just as in vivo, taurine-conjugated BA species were predominant in rat SCH, while glycine-conjugated BAs were predominant in human SCH. Total intracellular BAs remained relatively constant over days in culture in rat SCH. Total BAs in control (CTL) cells+bile, cells, and medium were approximately 3.4, 2.9, and 8.3-fold greater in human than in rat. The estimated intracellular concentrations of the measured total BAs were 64.3ýý5.9 ýýM in CTL rat and 183ýý56 ýýM in CTL human SCH, while medium concentrations of the total BAs measured were 1.16ýý0.21 ýýM in CTL rat SCH and 9.61ýý6.36 ýýM in CTL human SCH. Treatment of cells for 24h with 10 ýýM troglitazone (TRO), an inhibitor of the bile salt export pump (BSEP) and the Naýýý-taurocholate cotransporting polypeptide (NTCP), had no significant effect on endogenous BAs measured at the end of the 24-h culture period, potentially due to compensatory mechanisms that maintain BA homeostasis. These data demonstrate that BAs in SCH are similar to in vivo, and that SCH may be a useful in vitro model to study alterations in BA disposition if species differences are taken into account.

PubMed ID: 22342602 Exiting the NIEHS site

MeSH Terms: No MeSH terms associated with this publication

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