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Dose-related liver injury of Geniposide associated with the alteration in bile acid synthesis and transportation

التفاصيل البيبلوغرافية
العنوان: Dose-related liver injury of Geniposide associated with the alteration in bile acid synthesis and transportation
المؤلفون: Jingzhuo Tian, Jingjing Zhu, Yan Yi, Chunying Li, Yushi Zhang, Yong Zhao, Chen Pan, Shixie Xiang, Xiaolong Li, Guiqin Li, John W Newman, Xiaoyi Feng, Jing Liu, Jiayin Han, Lianmei Wang, Yue Gao, Michael R. La Frano, Aihua Liang
المصدر: Scientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
بيانات النشر: Nature Portfolio, 2017.
سنة النشر: 2017
المجموعة: LCC:Medicine
LCC:Science
مصطلحات موضوعية: Medicine, Science
الوصف: Abstract Fructus Gardenia (FG), containing the major active constituent Geniposide, is widely used in China for medicinal purposes. Currently, clinical reports of FG toxicity have not been published, however, animal studies have shown FG or Geniposide can cause hepatotoxicity in rats. We investigated Geniposide-induced hepatic injury in male Sprague-Dawley rats after 3-day intragastric administration of 100 mg/kg or 300 mg/kg Geniposide. Changes in hepatic histomorphology, serum liver enzyme, serum and hepatic bile acid profiles, and hepatic bile acid synthesis and transportation gene expression were measured. The 300 mg/kg Geniposide caused liver injury evidenced by pathological changes and increases in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and γ-glutamytransferase (γ-GT). While liver, but not sera, total bile acids (TBAs) were increased 75% by this dose, dominated by increases in taurine-conjugated bile acids (t-CBAs). The 300 mg/kg Geniposide also down-regulated expression of Farnesoid X receptor (FXR), small heterodimer partner (SHP) and bile salt export pump (BSEP). In conclusion, 300 mg/kg Geniposide can induce liver injury with associated changes in bile acid regulating genes, leading to an accumulation of taurine conjugates in the rat liver. Taurocholic acid (TCA), taurochenodeoxycholic acid (TCDCA) as well as tauro-α-muricholic acid (T-α-MCA) are potential markers for Geniposide-induced hepatic damage.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2045-2322
Relation: https://doaj.org/toc/2045-2322
DOI: 10.1038/s41598-017-09131-2
URL الوصول: https://doaj.org/article/9a2bafc487e94da097d5f878413fc998
رقم الأكسشن: edsdoj.9a2bafc487e94da097d5f878413fc998
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:20452322
DOI:10.1038/s41598-017-09131-2