Protective effect of obeticholic acid on cholestasis induced by subacute exposure to DEHP in mice
10.19405/j.cnki.issn1000-1492.2022.10.018
- Author:
Mingchao Qu
1
;
Fan Zhao
1
;
Cheng Zhang
2
;
Jiayi Zhang
1
;
Lu Ye
1
;
Lun Zhang
1
;
Yun Yu
1
;
Jianqing Wang
1
Author Information
1. Dept of Pharmacy, The Fourth Affiliated Hospital of Anhui Medical University, Hefei 230012
2. Dept of Toxicology,School of Public Health , Anhui Medical University, Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes , Hefei 230032
- Publication Type:Journal Article
- Keywords:
di (2⁃ethylhexyl) phthalate;
obeticholic acid;
cholestasis
- From:
Acta Universitatis Medicinalis Anhui
2022;57(10):1608-1613
- CountryChina
- Language:Chinese
-
Abstract:
Objective :To investigate the protective effect of obeticholic acid (OCA) on di(2⁃ethylhexyl) phthalate (DEHP)Ⅳinduced cholestasis in mice.
Methods :Animal experiment 1 : Female ICR mice were randomly divided into 3 groups: the control group, DEHP low⁃dose group [50 mg/(kg d)]and DEHP high⁃dose group [200 mg/ ( kg d)] . All mice were administered with DEHP by gavage for 18 days. Animal experiment 2: Female ICR mice were randomly divided into 4 groups: the control group, OCA group, DEHP model group[200 mg/(kg ·d)] and DEHP + OCA group. All mice were administered with DEHP by gavage for 18 days and the duration of OCA was 12 - 18 days. Serum and liver tissues of mice were collected. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bile acid ( TBA) levels, liver TBA levels, protein expression of farnesoid X receptor (FXR) and mRNA levels of FXR and SHP were detected. HE staining was used to observe the pathological changes in liver tissues.
Results :Experiment 1: Compared with the control group, the liver weight, liver coefficient and the TBA concentrations in serum and liver significantly increased only in DEHP[200 mg/(kg ·d)] group(P
< 0. 01), indicating that the modeling was successful. Animal experiment 2: Compared with the DEHP model group, the liver weight and liver coefficient significantly decreased after OCA treatment, and the TBA concentrations in serum and liver both decreased (P < 0. 01) .Compared with the control group, the protein expression level and its mRNA level of FXR decreased after DEHP[200 mg/(kg ·d)]treatment; Compared with the DEHP model group, the protein expression of FXR and the mRNA levels of FXR and SHP significantly increased after OCA treatment(P < 0. 05) .
Conclusion :DEHP exposure can induce cholestatic liver injury in mice, and OCA posttreatment has a protective effect on DEHP⁃induced cholestasis in mice.
- Full text:2024081121172964558奥贝胆酸对DEHP亚急性暴...导致小鼠胆汁淤积的保护作用_屈明超.pdf
