Evaluation of Serum Bile Acid Profiles as Biomarkers of Liver Injury in Rodents

Abstract Background ICP pregnant women have a unique profile of serum bile acid metabolis, early and accurate identification of ICP patients is beneficial to early appropriate treatment and improvement of pregnancy outcomes. In this study, ultra-high performance liquid chromatography-mass spectrometry/mass spectrometry (UPLC-MS/MS) was used to analyze the 15 types of serum bile acid profiles of ICP in third trimester, patients with cholelithiasis, and patients with hepatitis B virus. The ICP diagnostic model established by partial least squares-discriminant analysis (PLS-DA) was used to screen the differential bile acids for clinical subtypes of ICP. 144 cases of ICP patients were involved in this study, and were divided into four subgroups according to serum levels of TBA, DBIL, and ALT. Results ①The differential serum bile acid profiles of ICP group and normal pregnant women were DCA, TDCCA, TCA, GDCA and GLCA.②The differential serum bile acid profiles of the ICP1 group (ICP with jaundice) and normal pregnant women were TCDCA, TCA, GCA, GCDCA, TUDCA and GUDCA.③The differential serum bile acid profiles of the ICP3 group (hyperbiliary acidemia of pregnancy) and normal pregnant group was GUDCA, LCA, GLCA, UDCA, TUDCA, CDCA, and TLCA (P <0.05).④The differential serum bile acid profiles of ICP4 group (idiopathic aminotransferase abnormality during pregnancy) and normal pregnant group was UDCA, GUDCA, TUDCA, GCA and GLCA (P <0.05).⑤The occurrence of meconium-stained amniotic fluid, premature delivery and cesarean section in ICP1 group was significantly higher than normal group,ICP2 group,ICP3 group,and ICP4 group (P <0.05); The occurrence of meconium-stained amniotic fluid, premature delivery and cesarean section in ICP2 group, ICP3 group,and ICP4 group was significantly higher than normal group (P <0.05), but no difference was found among ICP2 group, ICP3 group,and ICP4 group (P> 0.05). Conclusion: Maternal serum bile acid profiles are useful to differentiate the four subtypes of ICP. ICP with jaundice could be an important predictor of adverse pregnancy outcomes of ICP.

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Development and Validation of a Highly Sensitive LC-MS/MS Method for the Analysis of Bile Acids in Serum, Plasma, and Liver Tissue Samples

Metabolites ◽

10.3390/metabo10070282 ◽

2020 ◽

Vol 10 (7) ◽

pp. 282

Author(s):

Cristina Gómez ◽

Simon Stücheli ◽

Denise V. Kratschmar ◽

Jamal Bouitbir ◽

Alex Odermatt

Keyword(s):

Bile Acid ◽

Liver Injury ◽

Bile Acids ◽

Liver Tissue ◽

Bioactive Molecules ◽

Rodent Species ◽

Drug Induced ◽

Tissue Samples ◽

Drug Induced Liver Injury ◽

Bile Acid Profiles

Bile acids control lipid homeostasis by regulating uptake from food and excretion. Additionally, bile acids are bioactive molecules acting through receptors and modulating various physiological processes. Impaired bile acid homeostasis is associated with several diseases and drug-induced liver injury. Individual bile acids may serve as disease and drug toxicity biomarkers, with a great demand for improved bile acid quantification methods. We developed, optimized, and validated an LC-MS/MS method for quantification of 36 bile acids in serum, plasma, and liver tissue samples. The simultaneous quantification of important free and taurine- and glycine-conjugated bile acids of human and rodent species has been achieved using a simple workflow. The method was applied to a mouse model of statin-induced myotoxicity to assess a possible role of bile acids. Treatment of mice for three weeks with 5, 10, and 25 mg/kg/d simvastatin, causing adverse skeletal muscle effects, did not alter plasma and liver tissue bile acid profiles, indicating that bile acids are not involved in statin-induced myotoxicity. In conclusion, the established LC-MS/MS method enables uncomplicated sample preparation and quantification of key bile acids in serum, plasma, and liver tissue of human and rodent species to facilitate future studies of disease mechanisms and drug-induced liver injury.

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Maternal bile acid profile and subtype analysis of intrahepatic cholestasis of pregnancy

Orphanet Journal of Rare Diseases ◽

10.1186/s13023-021-01887-1 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Yong Shao ◽

Siyu Chen ◽

Huan Li ◽

Qin Tang ◽

Di Xu

Keyword(s):

Mass Spectrometry ◽

Bile Acid ◽

Cesarean Section ◽

Amniotic Fluid ◽

Pregnant Women ◽

Pregnancy Outcomes ◽

Premature Delivery ◽

Serum Bile Acid ◽

Bile Acid Profiles ◽

Meconium Stained Amniotic Fluid

Abstract Background ICP pregnant women have a unique profile of serum bile acid metabolism, thus the early and accurate identification of ICP patients is beneficial to early appropriate treatment and improvement of pregnancy outcomes. In this study, ultra-high performance liquid chromatography-mass spectrometry/mass spectrometry (UPLC-MS/MS) was used to analyze the 15 types of serum bile acid profiles among patients with ICP in third trimester, patients with cholelithiasis, and patients with hepatitis B virus. The ICP diagnostic model established by partial least squares-discriminant analysis (PLS-DA) was used to screen the differential bile acids for clinical subtypes of ICP. 144 cases of ICP patients were involved in this study, and divided into four subgroups according to serum level of TBA, DBIL, and ALT. Results (1) The differential serum bile acid profiles of ICP group and normal pregnant women were DCA, TDCA, TCA, GDCA and GLCA. (2) The differential serum bile acid profiles of the ICP1 group (ICP with jaundice) and normal pregnant women were TCDCA, TCA, GCA, GCDCA, TUDCA and GUDCA. (3) The differential serum bile acid profiles of the ICP3 group (Hyperchoicemia of pregnancy) and normal pregnant group was GUDCA, LCA, GLCA, UDCA, TUDCA, CDCA, and TLCA (P < 0.05). (4) The differential serum bile acid profiles of ICP4 group (idiopathic aminotransferase abnormality during pregnancy) and normal pregnant group was UDCA, GUDCA, TUDCA, GCA and GLCA (P < 0.05). (5) The occurrence of meconium-stained amniotic fluid, premature delivery and cesarean section in ICP1 group was significantly higher than normal group, ICP2 group, ICP3 group, and ICP4 group (P < 0.05); The occurrence of meconium-stained amniotic fluid, premature delivery and cesarean section in ICP2 group, ICP3 group, and ICP4 group was significantly higher than normal group (P < 0.05), but no difference was found among ICP2 group, ICP3 group, and ICP4 group (P > 0.05). Conclusion Maternal serum bile acid profiles are useful to differentiate the four subtypes of ICP. ICP with jaundice could be an important predictor of adverse pregnancy outcomes of ICP.

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