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Obeticholic Acid - PubAg

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Last Updated: 16 October 2021

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A novel LC‐MS/MS method for simultaneous estimation of obeticholic acid, glyco‐obeticholic acid, tauro‐obeticholic acid in human plasma and its application to a pharmacokinetic study

A fast, robust, straightforward, selective, and sensitive fluid chromatography‐tandem mass spectrometry technique was established for the simultaneous estimate of obeticholic acid and its 2 pharmacologically active metabolites, glyco‐obeticholic acid, and tauro‐obeticholic acid in human plasma. The technique linearity was established over a focus series of 0. 410 to 120. 466 ng/mL for obeticholic acid, 0. 414 to 121. 708 ng/mL for glyco‐obeticholic acid, and 0. 255 to 75. 101 ng/mL for tauro‐obeticholic acid.

Source link: https://pubag.nal.usda.gov/catalog/7335284


Obeticholic Acid Inhibits Anxiety via Alleviating Gut Microbiota-Mediated Microglia Accumulation in the Brain of High-Fat High-Sugar Diet Mice

Stress and anxiety is among the difficulties of metabolic disorders. Below, we analyzed the product biochemical parameters and behavioral efficiency by open area and Morris water maze tests in HFHS diet-induced MDs mice after OCA treatment for 9 and 18 weeks.

Source link: https://pubag.nal.usda.gov/catalog/7321728


Metabolism of obeticholic acid in brown bullhead (Ameiurus nebulosus)

Evaluation of brownish bullhead bile by ultra efficiency fluid chromatography high-resolution mass spectrometry disclosed a series of bile acids similar to those discovered in human beings. Furthermore, metabolites of obeticholic acid and several hydroxy-obeticholic acid by-products were located, standing for normal pathways of primary and additional steroid metabolic process. Brown bullhead exposed to obeticholic acid at a dose of 100 mg/kg gave no obvious signs of distress or poisoning.

Source link: https://pubag.nal.usda.gov/catalog/6487714


Opposite effects of the FXR agonist obeticholic acid on Mafg and Nrf2 mediate the development of acute liver injury in rodent models of cholestasis

Obeticholic acid, the first in course of FXR agonist accepted for scientific usage, creates side effects consisting of intense liver decompensation when administered to cirrhotic patients with primary biliary cholangitis at more than advised dosages. In the here and now research we have checked out the role of FXR/MafG/NRF2 pathway in the advancement of liver toxicity brought on by OCA in rodent versions of cholestasis. Cholestasis was generated by bile duct ligation or administration of α-naphtyl-isothiocyanate to male Wistar rats and FXR ⁻/ ⁻ and FXR ⁺/ ⁺ mice. By RNAseq evaluation we found that FXR animosity efficiently reversed the transcription of over 2100 genetics modulated by OCA/ANIT treatment, consisting of Mafg and Nrf2 and their target genes Cyp7a1, Cyp8b1, Mat1a, Mat2a, Gss. In contrast, Nrf2 induction by sulforaphane was protective. Liver injury brought on by FXR agonism in cholestasis is FXR-dependent and is turned around by FXR and Mafg antagonism or Nrf2 induction.

Source link: https://pubag.nal.usda.gov/catalog/6926462


An ultra-performance liquid chromatography-tandem mass spectrometry method for the determination of obeticholic acid in rat plasma and its application in preclinical pharmacokinetic studies

Currently, ursodeoxycholic acid is the only clear clinical treatment for key biliary cholangitis. In current years, obeticholic acid incorporated with UDCA has been used in the PBC patients that were not sensitive to UDCA, or as monotherapy for PBC grown-up patients who are intolerant to UDCA. To establish and confirm a particular, sensitive and trustworthy tandem mass spectrometry method for the determination of obeticholic acid in rat plasma. Plasma examples were treated with liquid-- liquid removal. Multiple response tracking techniques were utilized to find particular precursor and product ions. The target ion pair of OCA was 419. 38 → 401. 22, and the IS was 285. 05 → 193. 02. The direct series of OCA in rat plasma was 0. 05-- 50 μg/ mL; the healing rate was 91. 34%-- 97. 37%. No substantial matrix effects in this study. A certain, reputable and delicate measurable analysis method was developed to identify OCA after oral/intravenous administration in rat plasma by means of UPLC-MS/MS.

Source link: https://pubag.nal.usda.gov/catalog/6443455

* Please keep in mind that all text is summarized by machine, we do not bear any responsibility, and you should always check original source before taking any actions

* Please keep in mind that all text is summarized by machine, we do not bear any responsibility, and you should always check original source before taking any actions