Evaluation of hepatotoxicity and cholestasis in rats treated with EtOH extract of Fructus Psoraleae

被引：87

作者：

Wang, Jiaying ^{[1
,2
]}

Jiang, Zhenzhou ^{[1
,2
]}

Ji, Jinzi ^{[1
,3
]}

Li, Yanyan ^{[1
,2
]}

Chen, Mi ^{[1
,3
]}

Wang, Yurong ^{[3
]}

Zhang, Yun ^{[1
,4
]}

Tai, Ting ^{[3
]}

Wang, Tao ^{[1
,2
]}

Zhang, Luyong ^{[1
,2
]}

机构：

[1] China Pharmaceut Univ, Jiangsu Prov Ctr Drug Screening, Nanjing 210009, Peoples R China

[2] China Pharmaceut Univ, Key Lab Drug Qual Control & Pharmacovigilance, Minist Educ, Nanjing 210009, Peoples R China

[3] Nanjing Univ Technol, Jiangsu Prov Ctr Safety Evaluat Drugs, Nanjing 210009, Peoples R China

[4] Shandong Acad Sci, Inst Biol, Jinan 250014, Shandong, Peoples R China

来源：

JOURNAL OF ETHNOPHARMACOLOGY | 2012年 / 144卷 / 01期

关键词：

EtOH extract of Fructus Psoraleae; Hepatotoxicity; Cholestasis; Transport; Bile acid; FXR; BILIARY CHOLESTEROL SECRETION; EXPORT PUMP MRP2; NUCLEAR RECEPTORS; LOCALIZATION; MECHANISMS; HEPATITIS;

D O I：

10.1016/j.jep.2012.08.028

中图分类号：

Q94 [植物学];

学科分类号：

071001 [植物学];

摘要：

Ethnopharmacological relevance: Fructus Psoraleae (FP) has been widely used to heal skin diseases as well as osteoporosis, osteomalacia, and bone fracture. There also exist many clinical reports about FP-induced hepatotoxicity associated with acute cholestatic hepatic injury. However, the FP-induced hepatotoxicity and the underlying mechanisms remain unclear. Aims of the study: The present study aims to determine the hepatotoxicity of FP in Sprague-Dawley (SD) rats and to investigate the underlying mechanisms. Materials and methods: Sprague-Dawley rats of both sexes were intragastrically administered with the EtOH extract of FP (EEFP) at doses of 1.875, 1.25 and 0.625 g/kg for 28 day. Body weight, relative liver weight, biochemical analysis, histopathology, the mRNA and protein expression of Cholesterol 7 alpha-hydroxylase (CYP7A1), farnesoid X receptor (FXR), bile-salt export pump (BSEP), multidrug resistance-associated protein 2 (MRP2), multidrug resistance-associated protein 3 (MRP3) were evaluated to study the EEFP-induced hepatotoxicity and its underlying mechanisms. Results: Many abnormalities were observed in the EEFP-treated groups including suppression of weight gain and food intake, change of some parameters in serum biochemistry, increased weight of liver, and decreased concentration of bile acid in bile. The mRNA and protein expression of CYP7A1, MRP3, MRP2, BSEP increased and the expression of FXR decreased in EEFP-treated female groups: the mRNA and protein of FXR and CYP7A1 decreased and that of the others remained the same in EEFP-treated male groups. Conclusion: In conclusion, we provide evidence for the first time that EEFP can induce sex-related cholestatic hepatotoxicity, and that female rats are more sensitive to EEFP-induced hepatotoxicity, which involves the destruction of the biosynthesis and transportation of bile acid. Further investigation is still needed to uncover the mechanism of the sex-dimorphic EEFP-induced hepatotoxicity. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

引用

页码：73 / 81

页数：9

共 36 条

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Constitutive and inducible hepatic cytochrome P450 isoforms in senescent male and female rats and response to low-dose phenobarbital [J].