Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
7614800 | Journal of Chromatography B | 2018 | 10 Pages |
Abstract
Nuclear receptors, such as the pregnane X receptor (PXR) and glucocorticoid receptor (GR), play an important role in regulating the homeostasis of bile acids (BAs). In previous studies, two-week treatment of 1â¯mg/kg of dexamethasone (DEX) was used to activate GR in mice, whereas 4-day treatment of 75â¯mg/kg of DEX was chosen to activate PXR. However, little is known about the effect of DEX on circulating and hepatic BA profiles. In the present study, we reported a simple and rapid LC-MS method for semi-quantitative profiling of 39 BA species in mouse serum and liver. This method was applied to investigate the BA profiles in mice treated with either 1â¯mg/kg DEX for two weeks or 75â¯mg/kg DEX for 4â¯days. The gene expression, microsomal induction and liver enlargement in mice confirmed that PXR was activated by 4-day treatment of 75â¯mg/kg DEX, but not by two-week treatment of 1â¯mg/kg DEX. Two-week treatment of 1â¯mg/kg DEX markedly increased the circulating BAs, in particular conjugated primary BAs, suggesting a pro-cholestatic effect of DEX at low doses. In contrast, 4-day treatment of 75â¯mg/kg DEX increased BA hydroxylation and decreased hepatic BAs, in particular unconjugated secondary BAs, suggesting a BA-lowering and bacteria-suppressive effect of DEX at high doses. To conclude, a semi-quantitative LC-MS method was developed and applied to elucidate the dosage-related effects of DEX on serum and hepatic BA profiles in mice.
Keywords
Related Topics
Physical Sciences and Engineering
Chemistry
Analytical Chemistry
Authors
Xue Wang, Fangyu Wang, Zhiqiang Lu, Xinghua Jin, Youcai Zhang,