An alternative approach to validation of liquid chromatography-mass spectrometry methods for the quantification of endogenous compounds

Uher, Martin; Mičuda, Stanislav; Kacerovský, Marian; Hroch, Miloš

doi:10.1016/j.chroma.2023.464173

Cited by 1 publication

(1 citation statement)

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“…Triglyceride levels in plasma and liver were measured using commercial kits (Erba Lachema s.r.o., Brno, Czech Republic) as previously described ( Igreja Sá et al , 2020 ). The concentration of BAs in plasma, bile, liver, small intestine, and feces was measured using a liquid chromatography-mass spectrometry (LC-MS) method as described previously ( Uher et al , 2023 ). A list of all quantified BAs are provided in the Supplementary data .…”

Section: Methodsmentioning

confidence: 99%

Carvedilol impairs bile acid homeostasis in mice: implication for nonalcoholic steatohepatitis

Lastuvkova,

Nova,

Hroch

et al. 2023

Toxicological Sciences

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Carvedilol is a widely used beta-adrenoreceptor antagonist for multiple cardiovascular indications; however, it may induce cholestasis in patients, but the mechanism for this effect is unclear. Carvedilol also prevents the development of various forms of experimental liver injury, but its effect on nonalcoholic steatohepatitis (NASH) is largely unknown. In this study, we determined the effect of carvedilol (10 mg/kg/day p.o.) on bile formation and bile acid (BA) turnover in male C57BL/6 mice consuming either a chow diet or a western-type NASH-inducing diet. BAs were profiled by LC-MS and BA-related enzymes, transporters, and regulators were evaluated by western blot analysis and qRT-PCR. In chow diet-fed mice, carvedilol increased plasma concentrations of BAs resulting from reduced BA uptake to hepatocytes via Ntcp transporter downregulation. Inhibition of the β-adrenoreceptor-cAMP-Epac1-Ntcp pathway by carvedilol may be the post-transcriptional mechanism underlying this effect. In contrast, carvedilol did not worsen the deterioration of BA homeostasis accompanying NASH; however, it shifted the spectra of BAs toward more hydrophilic and less toxic α-muricholic and hyocholic acids. This positive effect of carvedilol was associated with a significant attenuation of liver steatosis, inflammation, and fibrosis in NASH mice. In conclusion, our results indicate that carvedilol may increase BAs in plasma by modifying their liver transport. In addition, carvedilol provided significant hepatoprotection in a NASH murine model without worsening BA accumulation. These data suggest beneficial effects of carvedilol in patients at high risk for developing NASH.

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Section: Methodsmentioning

confidence: 99%