Disturbances of Bile Acid Metabolism in Parenchymal Liver Cell Disease

Vlahčevič, Z. Reno; Prugh, M.F.; Gregory, Daniel H.; Swell, Leon

doi:10.1016/s0300-5089(21)00384-9

Cited by 49 publications

(3 citation statements)

References 62 publications

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“…Hepatic dysfunction is known to be associated with disturbances in bile acid metabolism. − Formed from cholesterol in the liver, bile acids (BAs) are excreted in mammalian bile mainly as glycine or taurine conjugates. BAs then undergo further metabolism by bacterial and hepatic enzymes during enterohepatic circulation, and it is well-known that BA metabolism is co-dependent on the biological activities of the gut microflora. − In normal human individuals, BAs are detected predominantly in bile and feces, with considerably lower urine or serum levels.…”

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Ultra Performance Liquid Chromatography-Mass Spectrometry Profiling of Bile Acid Metabolites in Biofluids: Application to Experimental Toxicology Studies

et al. 2010

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We have developed an ultra performance liquid chromatography-mass spectrometry (UPLC-MS(E)) method to measure bile acids (BAs) reproducibly and reliably in biological fluids and have applied this approach for indications of hepatic damage in experimental toxicity studies. BAs were extracted from serum using methanol, and an Acquity HSS column coupled to a Q-ToF mass spectrometer was used to separate and identify 25 individual BAs within 5 min. Employing a gradient elution of water and acetonitrile over 21 min enabled the detection of a wide range of endogenous metabolites, including the BAs. The utilization of MS(E) allowed for characteristic fragmentation information to be obtained in a single analytical run, easily distinguishing glycine and taurine BA conjugates. The proportions of these conjugates were altered markedly in an experimental toxic state induced by galactosamine exposure in rats. Principally, taurine-conjugated BAs were greatly elevated ( approximately 50-fold from control levels), and were highly correlated to liver damage severity as assessed by histopathological scoring (r = 0.83), indicating their potential as a sensitive measure of hepatic damage. The UPLC-MS approach to BA analysis offers a sensitive and reproducible tool that will be of great value in exploring both markers and mechanisms of hepatotoxicity and can readily be extended to clinical studies of liver damage.

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Ultra Performance Liquid Chromatography-Mass Spectrometry Profiling of Bile Acid Metabolites in Biofluids: Application to Experimental Toxicology Studies

et al. 2010

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“…both cholic acid and chenodeoxycholic acid are conjugated. at the carboxylic acid carbon, with an amino acid (either glycine or taurine) (2,4,5). During passage through the distal small intestine and colon.…”

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“…The initial step in the synthesis of both bile acids. the 7a-hydroxylation of cholesterol, occurs under the influence of the rate-limiting enzyme for bile acid synthesis, 7a-hydroxylase (5). This reaction is regulated by the influx of bile acids to the liver.…”

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confidence: 99%