Individual serum bile acid profiling in rats aids in human risk assessment of drug-induced liver injury due to BSEP inhibition

Uterine fibroids are the most common pelvic tumor formation in women and the most common indication for hysterectomy. The effectiveness of long-term intermittent use of ulipristal acetate (UA) in patients with uterine myoma has been proven earlier. In May 2018, the ability of UA to cause a drug-induced liver injury (drug-induced liver injury, DILI) was disproved, and the European Commission approved a positive decision. According to the conclusion Expertise of the Pharmacovigilance Risk Assessment Committee (Pharmacovigilance Risk Assessment Committee - PRAC) the benefit/risk ratio remains favorable. Published recommendations are aimed at reducing the risk of liver damage. UA remains the 1st line of treatment for most myomas.

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Development of Blood Biomarkers for Drug-Induced Liver Injury: An Evaluation of Their Potential for Risk Assessment and Diagnostics

Molecular Diagnosis & Therapy ◽

10.1007/s40291-013-0049-0 ◽

2013 ◽

Vol 17 (6) ◽

pp. 343-354 ◽

Cited By ~ 30

Author(s):

David E. Amacher ◽

Shelli J. Schomaker ◽

Jiri Aubrecht

Keyword(s):

Risk Assessment ◽

Liver Injury ◽

Blood Biomarkers ◽

Drug Induced ◽

Drug Induced Liver Injury

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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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