ArticleBritish journal of pharmacology2021
The ratio of ursodeoxycholyltaurine to 7-oxolithocholyltaurine serves as a biomarker of decreased 11β-hydroxysteroid dehydrogenase 1 activity in mouse.
Article in British journal of pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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4 citing papers in PubMed.
- Alterations in glucocorticoid homeostasis following sleeve gastrectomy.bioRxiv : the preprint server for biology · 2025Article
- Albendazole reduces hepatic inflammation and endoplasmic reticulum-stress in a mouse model of chronic Echinococcus multilocularis infection.PLoS neglected tropical diseases · 2022Article
- Targeted bile acid profiles reveal the liver injury amelioration of Da-Chai-Hu decoction against ANIT- and BDL-induced cholestasis.Frontiers in pharmacology · 2022Article
- The ratio of ursodeoxycholyltaurine to 7-oxolithocholyltaurine serves as a biomarker of decreased 11β-hydroxysteroid dehydrogenase 1 activity in mouse.British journal of pharmacology · 2021Article
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Abstract
background and purpose11β-Hydroxysteroid dehydrogenase 1 (11β-HSD1) regulates tissue-specific glucocorticoid metabolism and its impaired expression and activity are associated with major diseases. Pharmacological inhibition of 11β-HSD1 is considered a promising therapeutic strategy. This study investigated whether alternative 7-oxo bile acid substrates of 11β-HSD1 or the ratios to their 7-hydroxy products can serve as biomarkers for decreased enzymatic activity. EXPERIMENTAL APPROACH: Bile acid profiles were measured by ultra-HPLC tandem-MS in plasma and liver tissue samples of four different mouse models with decreased 11β-HSD1 activity: global (11KO) and liver-specific 11β-HSD1 knockout mice (11LKO), mice lacking hexose-6-phosphate dehydrogenase (H6pdKO) that provides cofactor NADPH for 11β-HSD1 and mice treated with the pharmacological inhibitor carbenoxolone. Additionally, 11β-HSD1 expression and activity were assessed in H6pdKO- and carbenoxolone-treated mice. KEY
resultsThe enzyme product to substrate ratios were more reliable markers of 11β-HSD1 activity than absolute levels due to large inter-individual variations in bile acid concentrations. The ratio of the 7β-hydroxylated ursodeoxycholyltaurine (UDC-Tau) to 7-oxolithocholyltaurine (7oxoLC-Tau) was diminished in plasma and liver tissue of all four mouse models and decreased in H6pdKO- and carbenoxolone-treated mice with moderately reduced 11β-HSD1 activity. The persistence of 11β-HSD1 oxoreduction activity in the face of H6PD loss indicates the existence of an alternative NADPH source in the endoplasmic reticulum. CONCLUSIONS AND IMPLICATIONS: The plasma UDC-Tau/7oxo-LC-Tau ratio detects decreased 11β-HSD1 oxoreduction activity in different mouse models. This ratio may be a useful biomarker of decreased 11β-HSD1 activity in pathophysiological situations or upon pharmacological inhibition. LINKED ARTICLES: This article is part of a themed issue on Oxysterols, Lifelong Health and Therapeutics. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.16/issuetoc.
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