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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/06/20 08:34:49」(JST)

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English Journal

Evaluation of serum bile Acid profiles as biomarkers of liver injury in rodents.

Luo L, Schomaker S, Houle C, Aubrecht J, Colangelo JL.Author information * Biomarkers of Drug Safety Research and Development and.AbstractBile acids (BAs) have been studied as potential biomarkers of drug-induced liver injury. However, the relationship between levels of individual BAs and specific forms of liver injury remains to be fully understood. Thus, we set out to evaluate cholic acid (CA), glycocholic acid (GCA), and taurocholic acid (TCA) as potential biomarkers of liver injury in rodent toxicity studies. We have developed a sensitive liquid chromatography-tandem mass spectrometry (LC/MS/MS) assay applicable to rat and mouse serum and evaluated levels of the individual BAs in comparison with the classical biomarkers of hepatotoxicity (alanine aminotransferase [ALT], aspartate aminotransferase [AST], glutamate dehydrogenase (GLDH), alkaline phosphatase, total bilirubin, gamma-glutamyl transferase, and total BAs) and histopathology findings in animals treated with model toxicants. The pattern of changes in the individual BAs varied with different forms of liver injury. Animals with histopathologic signs of hepatocellular necrosis showed increases in all 3 BAs tested, as well as increases in ALT, AST, GLDH, and total BAs. Animals with histopathologic signs of bile duct hyperplasia (BDH) displayed increases in only conjugated BAs (GCA and TCA), a pattern not observed with the other toxicants. Because BDH is detectable only via histopathology, our results indicate the potential diagnostic value of examining individual BAs levels in serum as biomarkers capable of differentiating specific forms of liver injury in rodent toxicity studies.
Toxicological sciences : an official journal of the Society of Toxicology.Toxicol Sci.2014 Jan;137(1):12-25. doi: 10.1093/toxsci/kft221. Epub 2013 Oct 1.
Bile acids (BAs) have been studied as potential biomarkers of drug-induced liver injury. However, the relationship between levels of individual BAs and specific forms of liver injury remains to be fully understood. Thus, we set out to evaluate cholic acid (CA), glycocholic acid (GCA), and taurocholi
PMID 24085190

The feline bile salt export pump: a structural and functional comparison with canine and human Bsep/BSEP.

van Beusekom CD, van den Heuvel JJ, Koenderink JB, Schrickx JA, Russel FG.AbstractBACKGROUND: The bile salt export pump (BSEP/ABCB11) is the primary transporter for the excretion of bile acids from hepatocytes into bile. In human, inhibition of BSEP by drugs has been related to drug-induced cholestasis and subsequent cytotoxic effects. The role of BSEP in canine and feline liver diseases has not been studied in detail, but the same mechanism of inhibition by drugs as in humans could play a role in veterinary medicine. The aim of this study was to investigate the functional characteristics of feline Bsep in comparison with canine and human Bsep/BSEP with respect to substrate affinities and inhibitory potential of model drugs. Orthologs of all three species were cloned and cell membrane vesicles overexpressing feline, canine and human Bsep/BSEP were prepared for functional analyses.
BMC veterinary research.BMC Vet Res.2013 Dec 20;9(1):259. [Epub ahead of print]
BACKGROUND: The bile salt export pump (BSEP/ABCB11) is the primary transporter for the excretion of bile acids from hepatocytes into bile. In human, inhibition of BSEP by drugs has been related to drug-induced cholestasis and subsequent cytotoxic effects. The role of BSEP in canine and feline liver
PMID 24359682

Clinical application of transcriptional activators of bile salt transporters.

Baghdasaryan A1, Chiba P2, Trauner M3.Author information 1Hans Popper Laboratory of Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Austria; Laboratory of Experimental and Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Austria.2Institute of Medical Chemistry, Medical University of Vienna, Austria.3Hans Popper Laboratory of Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Austria. Electronic address: michael.trauner@meduniwien.ac.at.AbstractHepatobiliary bile salt (BS) transporters are critical determinants of BS homeostasis controlling intracellular concentrations of BSs and their enterohepatic circulation. Genetic or acquired dysfunction of specific transport systems causes intrahepatic and systemic retention of potentially cytotoxic BSs, which, in high concentrations, may disturb integrity of cell membranes and subcellular organelles resulting in cell death, inflammation and fibrosis. Transcriptional regulation of canalicular BS efflux through bile salt export pump (BSEP), basolateral elimination through organic solute transporters alpha and beta (OSTα/OSTβ) as well as inhibition of hepatocellular BS uptake through basolateral Na+-taurocholate cotransporting polypeptide (NTCP) represent critical steps in protection from hepatocellular BS overload and can be targeted therapeutically. In this article, we review the potential clinical implications of the major BS transporters BSEP, OSTα/OSTβ and NTCP in the pathogenesis of hereditary and acquired cholestatic syndromes, provide an overview on transcriptional control of these transporters by the key regulatory nuclear receptors and discuss the potential therapeutic role of novel transcriptional activators of BS transporters in cholestasis.
Molecular aspects of medicine.Mol Aspects Med.2013 Dec 12. pii: S0098-2997(13)00082-4. doi: 10.1016/j.mam.2013.12.001. [Epub ahead of print]
Hepatobiliary bile salt (BS) transporters are critical determinants of BS homeostasis controlling intracellular concentrations of BSs and their enterohepatic circulation. Genetic or acquired dysfunction of specific transport systems causes intrahepatic and systemic retention of potentially cytotoxic
PMID 24333169

Japanese Journal

Adsorption of Bile Acid by Chitosan-Orotic Acid Salt and Its Application as an Oral Preparation

Murata Yoshifumi,Kudo Sayuri,Kofuji Kyouko [他],MIYAMOTO Etsuko,KAWASHIMA Susumu
Chemical & pharmaceutical bulletin 52(10), 1183-1185, 2004-10-01
… When taurocholate (TCA) and glycocholate (GCA) were present together in the medium, CS-OT adsorbed identical amounts of both bile acids. …
NAID 110003615506

Evaluation of Insulin Permeability and Effects of Absorption Enhancers on Its Permeability by an in Vitro Pulmonary Epithelial System Using Xenopus Pulmonary Membrane

Yamamoto Akira,Tanaka Hideaki,Okumura Shigeki [他],SHINSAKO Keiko,ITO Mayuko,YAMASHITA Masahiro,OKADA Naoki,FUJITA Takuya,MURANISHI Shozo
Biological & pharmaceutical bulletin 24(4), 385-389, 2001-04-01
… Absorption enhancers used in this study were sodium caprate(NaCap), sodium glycocholate(NaGC), sodium salicylate(NaSal) and ethylenediaminetetraacetic acid disodium salt(EDTA). …
NAID 110003638476

Electrophysiological Studies on the Evaluation of Absorption Enhancers in Caco-2 Cells Using a Microelectrode Technique

Quan Ying-Shu,Fujita Takuya,Kamiyama Fumio [他],YAMAMOTO Akira
Biological & pharmaceutical bulletin 23(6), 738-742, 2000-06-01
… In the electrophysiological study with absorption enhancers, laurylmaltoside (LM) markedly decreased the V_m value, while sodium glycocholate(NaGC) moderately reduced this value, and EDTA did not affect the value. …
NAID 110003640057

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★リンクテーブル★

リンク元	「glycocholic acid」「グリココール酸」

「glycocholic acid」

Glycocholic acid
	IUPAC name Glycocholic acid
Identifiers
CAS number	475-31-0
PubChem	10140
ChemSpider	9734
UNII	G59NX3I3RT
ChEBI	CHEBI:17687
ChEMBL	CHEMBL411070
Jmol-3D images	Image 1
	SMILES C[C@H](CCC(=O)NCC(=O)O)[C@H]1CC[C@@H]2[C@@]1([C@H](C[C@H]3[C@H]2[C@@H](C[C@H]4[C@@]3(CC[C@H](C4)O)C)O)O)C ;
	InChI InChI=1S/C26H43NO6/c1-14(4-7-22(31)27-13-23(32)33)17-5-6-18-24-19(12-21(30)26(17,18)3)25(2)9-8-16(28)10-15(25)11-20(24)29/h14-21,24,28-30H,4-13H2,1-3H3,(H,27,31)(H,32,33)/t14-,15+,16-,17-,18+,19+,20-,21+,24+,25+,26-/m1/s1 ; Key: RFDAIACWWDREDC-FRVQLJSFSA-N InChI=1/C26H43NO6/c1-14(4-7-22(31)27-13-23(32)33)17-5-6-18-24-19(12-21(30)26(17,18)3)25(2)9-8-16(28)10-15(25)11-20(24)29/h14-21,24,28-30H,4-13H2,1-3H3,(H,27,31)(H,32,33)/t14-,15+,16-,17-,18+,19+,20-,21+,24+,25+,26-/m1/s1; Key: RFDAIACWWDREDC-FRVQLJSFBG ;
Properties
Molecular formula	C26H43NO6
Molar mass	465.631 g/mol
Melting point	130 °C
	Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
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	Infobox references