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https://www.readbyqxmd.com/read/28645914/bile-salt-homeostasis-in-normal-and-bsep-gene-knock-out-rats-with-single-and-repeated-doses-of-troglitazone
#1
Yaofeng Cheng, Shenjue Chen, Chris Freeden, Weiqi Chen, Yueping Zhang, Pamela Abraham, David Nelson, William G Humphreys, Jinpin Gan, Yurong Lai
The interference of bile acid secretion through bile salt export pump (BSEP) inhibition was one of the mechanisms for troglitazone (TGZ) induced hepatotoxicity. Here we investigated the impact of single or repeated oral doses of TGZ (200 mg/kg/day, 7 days) on bile acid homoeostasis in wild-type (WT) and Bsep KO rats. Following oral doses, plasma exposures of TGZ were not different between WT and KO rats, and were similar on Day-1 and Day-7. However, plasma exposures of the major metabolite, troglitazone sulfate (TS), in KO rats were 7...
June 23, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28639266/bakuchiol-contributes-to-the-hepatotoxicity-of-psoralea-corylifolia-in-rats
#2
Zhi-Jian Li, Abudumijiti Abulizi, Guo-Lin Zhao, Tao Wang, Fan Zhou, Zhen-Zhou Jiang, Silafu Aibai, Lu-Yong Zhang
Psoralea corylifolia L. (Fructus Psoraleae) is widely used in Asia, but there are concerns about hepatotoxicity caused by constituents such as psoralens and bakukiol. Bakuchiol (BAK) has antiinflammatory, antipyretic, antibacterial antiviral, anticancer, and estrogenic activity but appears to be hepatotoxic in in vitro tests. This study investigated the hepatotoxicity in vivo in rats. Using intragastrically administered bakuchiol at doses of 52.5 and 262.5 mg/kg for 6 weeks. Bodyweight, relative liver weight, biochemical indicators, histopathology, mRNA expression of CYP7A1, HMG-CoA reductase, BSEP, PPARα, SREBP-2, and MRP3 were measured...
June 22, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/28629595/a-novel-intestinal-restricted-fxr-agonist
#3
Hong Wang, Zhou Zhao, Jiyu Zhou, Yitong Guo, Guangji Wang, Haiping Hao, Xiaowei Xu
In this study, a new intestinal-restricted FXR agonist named fexaramine-3 (Fex-3) was developed and investigated both in vitro and in vivo. Fex-3 could selectively activate intestinal FXR and promote the expression of BSEP and SHP while suppressing CYP7A1 which is involved in bile acids syntheses better than the reported intestinal-restricted FXR agonist fexaramine (Fex). We demonstrated that Fex-3 targeted on FXR in ileum and has better selectivity than Fex. And the study of utilizing Fex-3 to reduce obesity was undergoing...
June 3, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28623919/effects-of-karela-bitter-melon-momordica-charantia-on-genes-of-lipids-and-carbohydrates-metabolism-in-experimental-hypercholesterolemia-biochemical-molecular-and-histopathological-study
#4
Dalia Yossri Saad, Mohamed Mohamed Soliman, Ahmed A Baiomy, Magdy Hassan Yassin, Hanan Basiouni El-Sawy
BACKGROUND: Hypercholesterolemia is a serious diseases associated with type-2 diabetes, atherosclerosis, cardiovascular disorders and liver diseases. Humans seek for safe herbal medication such as karela (Momordica charantia/bitter melon) to treat such disorders to avoid side effect of pharmacotherapies widely used. METHODS: Forty male Wistar rats were divided into four equal groups; control group with free access to food and water, cholesterol administered group (40 mg/kg BW orally); karela administered group (5 g /kg BW orally) and mixture of cholesterol and karela...
June 17, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28576870/role-of-mir-383-and-mir-146b-in-different-propensities-to-obesity-in-male-mice
#5
Shu-Fang Xia, Xiao-Mei Duan, Xiang-Rong Cheng, Li-Mei Chen, Yan-Jun Kang, Peng Wang, Xue Tang, Yong-Hui Shi, Guowei Le
The study was designed to investigate the possible mechanisms of hepatic microRNAs (miRs) in regulating local thyroid hormone (TH) action and ultimately different propensities to high-fat diet (HFD) induced obesity. When obesity-prone (OP) and obesity-resistant (OR) mice were fed high-fat diet for 7 weeks, OP mice showed apparent hepatic steatosis, with significantly higher body weight and lower hepatic thyroid hormone receptor b (TRb) expression and type 1 deiodinase (DIO1) activity than OR mice. Next-generation sequencing technology revealed that 13 miRs in liver were dysregulated between the two phenotypes, of which 8 miRs were predicted to target on Dio1 or TRb...
June 2, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28570655/circulating-fgf19-closely-correlates-with-bile-acid-synthesis-and-cholestasis-in-patients-with-primary-biliary-cirrhosis
#6
Zhanyi Li, Bingliang Lin, Guoli Lin, Yuankai Wu, Yusheng Jie, Xiangyong Li, Brian Ko, Yutian Chong, Jian Luo
BACKGROUND AND AIM: Bile acid (BA) synthesis in the liver is regulated by Fibroblast Growth Factor 19 (FGF19) secreted from the ileum as an enterohepatic feedback mechanism. Although FGF19 mRNA is absent in normal liver, FGF19 gene expression was reported to increase in response to both extrahepatic and intrahepatic cholestasis. The impact of upregulated FGF19 expression on BA synthesis is unclear and the overall role of circulating FGF19 and BA synthesis under cholestatic conditions needs to be further investigated...
2017: PloS One
https://www.readbyqxmd.com/read/28549656/glycyrrhizin-and-glycyrrhetinic-acid-inhibits-alpha-naphthyl-isothiocyanate-induced-liver-injury-and-bile-acid-cycle-disruption
#7
Haina Wang, Zhong-Ze Fang, Ran Meng, Yun-Feng Cao, Naoki Tanaka, Kristopher W Krausz, Frank J Gonzalez
Alpha-naphthyl isothiocyanate (ANIT) is a common hepatotoxicant experimentally used to reproduce the pathologies of drug-induced liver injury in humans, but the mechanism of its toxicity remains unclear. To determine the metabolic alterations following ANIT exposure, metabolomic analyses was performed by use of liquid chromatography-mass spectrometry. Partial least squares discriminant analysis (PLS-DA) of liver, serum, bile, ileum, and cecum of vehicle- and ANIT-treated mice revealed significant alterations of individual bile acids, including increased tauroursodeoxycholic acid, taurohydrodeoxycholic acid, taurochenodeoxycholic acid, and taurodeoxycholic acid, and decreased ω-, β- and tauro-α/β- murideoxycholic acid, cholic acid, and taurocholic acid in the ANIT-treated groups...
May 23, 2017: Toxicology
https://www.readbyqxmd.com/read/28549616/pectin-penta-oligogalacturonide-reduces-cholesterol-accumulation-by-promoting-bile-acid-biosynthesis-and-excretion-in-high-cholesterol-fed-mice
#8
Ru-Gang Zhu, Yan-Di Sun, Yu-Ting Hou, Jun-Gang Fan, Gang Chen, Tuo-Ping Li
Haw pectin penta-oligogalacturonide (HPPS) has important role in improving cholesterol metabolism and promoting the conversion of cholesterol to bile acids (BA) in mice fed high-cholesterol diet (HCD). However, the mechanism is not clear. This study aims to investigate the effects of HPPS on cholesterol accumulation and the regulation of hepatic BA synthesis and transport in HCD-fed mice. Results showed that HPPS significantly decreased plasma and hepatic TC levels but increased plasma high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I (apoA-I) levels, compared to HCD...
June 25, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28549240/dietary-salecan-reverts-partially-the-metabolic-gene-expressions-and-nmr-based-metabolomic-profiles-from-high-fat-diet-induced-obese-rats
#9
Qi Sun, Minghui Li, Xiao Yang, Xi Xu, Junsong Wang, Jianfa Zhang
Previous studies suggest that dietary salecan (a water-soluble β-glucan) effectively reduces high-fat-diet-induced adiposity through disturbing bile-acid-promoted emulsification in mice. However, the effects of salecan on metabolic genes and metabolites involved in lipid accumulation are mostly unknown. Here, we confirmed that dietary 3% and 6% salecan for 4 weeks markedly decreased fat accumulation in liver and adipose tissue in high-fat-diet rats, displaying a decrease in mRNA levels of SREBP1-C, FAS, SCD1 and ACC1 involved in de novo lipogenesis and a reduction of levels of GPAT1, DGAT1 and DGAT2 related to triglyceride synthesis...
May 5, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28536529/activation-of-sirt1-fxr-signaling-pathway-attenuates-triptolide-induced-hepatotoxicity-in-rats
#10
Jing Yang, Lixin Sun, Lu Wang, Hozeifa M Hassan, Xuan Wang, Phillip B Hylemon, Tao Wang, Huiping Zhou, Luyong Zhang, Zhenzhou Jiang
Triptolide (TP), a diterpenoid isolated from Tripterygium wilfordii Hook F, has an excellent pharmacological profile of immunosuppression and anti-tumor activities, but its clinical applications are severely restricted due to its severe and cumulative toxicities. The farnesoid X receptor (FXR) is the master bile acid nuclear receptor and plays an important role in maintaining hepatic metabolism homeostasis. Hepatic Sirtuin (Sirt1) is a key regulator of the FXR signaling pathway and hepatic metabolism homeostasis...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28536109/effect-of-iron-on-cholesterol-7-alpha-hydroxylase-expression-in-alcohol-induced-hepatic-steatosis-in-mouse
#11
Huan Liang, Hui Huang, Pei-Zhu Tan, Ying Liu, Jun-Hui Nie, Yi-Tong Zhang, Kai-Li Zhang, Yan Diao, Qi He, Bao-Yu Hou, Ting-Ting Zhao, Yan-Ze Li, Gui-Xiang Lv, Ki-Yong Lee, Xu Gao, Ling-Yun Zhou
Both iron and lipids are involved in the progression of alcoholic fatty liver disease (AFLD), but the interaction between iron and lipids in AFLD is unclear. Here, we tested the hypothesis that iron regulates the expression of genes involved in lipid metabolism through iron regulatory proteins (IRPs), which interact with the iron-responsive elements (IREs) in the UTRs of genes, resulting in lipid accumulation. Using the "RNA structure software", we predicted the mRNA secondary structures of more than 100 genes involved in lipid metabolism to investigate whether the IRE structure exists in novel mRNAs...
May 23, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28533986/atorvastatin-alters-the-expression-of-genes-related-to-bile-acid-metabolism-and-circadian-clock-in-livers-of-mice
#12
Wen-Kai Li, Huan Li, Yuan-Fu Lu, Ying-Ying Li, Zidong Donna Fu, Jie Liu
AIM: Atorvastatin is a HMG-CoA reductase inhibitor used for hyperlipidemia. Atorvastatin is generally safe but may induce cholestasis. The present study aimed to examine the effects of atorvastatin on hepatic gene expression related to bile acid metabolism and homeostasis, as well as the expression of circadian clock genes in livers of mice. METHODS: Adult male mice were given atorvastatin (10, 30, and 100 mg/kg, po) daily for 30 days, and blood biochemistry, histopathology, and gene expression were examined...
2017: PeerJ
https://www.readbyqxmd.com/read/28501703/xanthohumol-a-hop-derived-prenylated-flavonoid-promotes-macrophage-reverse-cholesterol-transport
#13
Hiroshi Hirata, Harumi Uto-Kondo, Masatsune Ogura, Makoto Ayaori, Kazusa Shiotani, Ami Ota, Youichi Tsuchiya, Katsunori Ikewaki
Xanthohumol, a prominent prenyl flavonoid from the hop plant (Humulus lupulus L.), is suggested to be antiatherogenic since it reportedly increases high-density lipoprotein (HDL) cholesterol levels. It is not clear whether xanthohumol promotes reverse cholesterol transport (RCT), the most important antiatherogenic property of HDL; therefore, we investigated the effects of xanthohumol on macrophage-to-feces RCT using a hamster model as a CETP-expressing species. In vivo RCT experiments showed that xanthohumol significantly increased fecal appearance of the tracer derived from intraperitoneally injected [(3)H]-cholesterol-labeled macrophages...
April 22, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28498614/hepatic-uptake-of-conjugated-bile-acids-is-mediated-by-both-ntcp-and-oatps-and-modulated-by-intestinal-sensing-of-plasma-bile-acid-levels-in-mice
#14
Davor Slijepcevic, Reinout L P Roscam Abbing, Takeshi Katafuchi, Antje Blank, Joanne M Donkers, Stéphanie van Hoppe, Dirk R de Waart, Dagmar Tolenaars, Jonathan H M van der Meer, Manon Wildenberg, Ulrich Beuers, Ronald P J Oude Elferink, Alfred H Schinkel, Stan F J van de Graaf
BACKGROUND & AIMS: The Na(+) -taurocholate cotransporting polypeptide (NTCP/SLC10A1) is believed to be pivotal for hepatic uptake of conjugated bile acids. However, plasma bile acid levels are normal in a subset of NTCP knockout mice and in mice treated with myrcludex B, a specific NTCP inhibitor. Here, we elucidated which transport proteins mediate the hepatic uptake of conjugated bile acids and demonstrated intestinal sensing of elevated bile acid levels in plasma in mice. METHODS: Mice or healthy volunteers were treated with myrcludex B...
May 12, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28474246/pectin-penta-oligogalacturonide-suppresses-intestinal-bile-acids-absorption-and-downregulates-the-fxr-fgf15-axis-in-high-cholesterol-fed-mice
#15
Rugang Zhu, Yuting Hou, Yandi Sun, Tuoping Li, Jungang Fan, Gang Chen, Junxiu Wei
Haw pectin penta-oligogalacturonide (HPPS), purified from the hydrolysates of haw pectin, has important role in decreasing hepatic cholesterol accumulation and promoting bile acids (BA) excretion in the feces of mice fed a high-cholesterol diet (HCD). However, the mechanism is not clear. This study aims to investigate the effects of HPPS on BA reabsorption in ileum and biosynthesis in liver of mice. Results showed that HPPS increased fecal BA output by approximately 110%, but decreased ileal BA and the total BA pool size by approximately 47 and 36%, respectively, compared to HCD...
May 4, 2017: Lipids
https://www.readbyqxmd.com/read/28445152/multiplexed-gene-expression-profiling-identifies-the-fgfr4-pathway-as-a-novel-biomarker-in-intrahepatic-cholangiocarcinoma
#16
Changhoon Yoo, Jihoon Kang, Deokhoon Kim, Kyu-Pyo Kim, Baek-Yeol Ryoo, Seung-Mo Hong, Jung Jin Hwang, Seong-Yun Jeong, Shin Hwang, Ki-Hun Kim, Young-Joo Lee, Klaus P Hoeflich, Oleg Schmidt-Kittler, Stephen Miller, Eun Kyung Choi
BACKGROUND: The fibroblast growth factor receptor 4 (FGFR4) pathway is an essential regulatory component of bile acid synthesis, and its relationship with hepatocellular carcinoma (HCC) has been reported. We investigated the gene expression and clinical significance of FGFR4 and related pathways in intrahepatic cholangiocarcinoma (iCCA). RESULTS: The median age was 56 years (range 30-78) and 34 patients (74%) were male. Six patients (13%) had hepatitis B virus infection, with or without liver cirrhosis...
June 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28424617/targeting-bile-acid-receptors-discovery-of-a-potent-and-selective-farnesoid-x-receptor-agonist-as-a-new-lead-in-the-pharmacological-approach-to-liver-diseases
#17
Carmen Festa, Simona De Marino, Adriana Carino, Valentina Sepe, Silvia Marchianò, Sabrina Cipriani, Francesco S Di Leva, Vittorio Limongelli, Maria C Monti, Angela Capolupo, Eleonora Distrutti, Stefano Fiorucci, Angela Zampella
Bile acid (BA) receptors represent well-defined targets for the development of novel therapeutic approaches to metabolic and inflammatory diseases. In the present study, we report the generation of novel C-3 modified 6-ethylcholane derivatives. The pharmacological characterization and molecular docking studies for the structure-activity rationalization, allowed the identification of 3β-azido-6α-ethyl-7α-hydroxy-5β-cholan-24-oic acid (compound 2), a potent and selective FXR agonist with a nanomolar potency in transactivation assay and high efficacy in the recruitment of SRC-1 co-activator peptide in Alfa Screen assay...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28364638/nrf2-is-crucial-for-the-down-regulation-of-cyp7a1-induced-by-arachidonic-acid-in-hepg2-cells
#18
Jin-Ming Zhang, Xing-He Wang, Li-Hong Hao, He Wang, Xiu-Ying Zhang, Ishfaq Muhammad, Yue Qi, Guang-Liang Li, Xiao-Qi Sun
In former research, cyp7a1 expression was decreased but Nrf2 transcription and hepatic arachidonic acid (AA) concentration were increased in high-fat diet fed mice. This study aims to investigate the influence of AA in CYP7A1 expression and the role of Nrf2 in regulating CYP7A1 in the process. HepG2 cells were administered with different concentrations of AA. Nrf2 and CYP7A1 expressions were analyzed by real-time PCR and western blot. Nrf2 silenced and over-expressed cell models were constructed by Nrf2 siRNA and eukaryotic expression vector transient transfections and were used to investigate the role of Nrf2 in regulating CYP7A1 following AA administration...
March 7, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/28357032/meta-analysis-reveals-up-regulation-of-cholesterol-processes-in-non-alcoholic-and-down-regulation-in-alcoholic-fatty-liver-disease
#19
Wasco Wruck, James Adjaye
AIM: To compare transcriptomes of non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) in a meta-analysis of liver biopsies. METHODS: Employing transcriptome data from patient liver biopsies retrieved from several public repositories we performed a meta-analysis comparing ALD and NAFLD. RESULTS: We observed predominating commonalities at the transcriptome level between ALD and NAFLD, most prominently numerous down-regulated metabolic pathways and cytochrome-related pathways and a few up-regulated pathways which include ECM-receptor interaction, phagosome and lysosome...
March 18, 2017: World Journal of Hepatology
https://www.readbyqxmd.com/read/28356314/high-throughput-and-reliable-isotope-label-free-approach-for-profiling-24-metabolic-enzymes-in-fvb-mice-and-gender-differences
#20
Jiamei Chen, Lijun Zhu, Xiaoyan Li, Haihui Zheng, Tongmeng Yan, Cong Xie, Sijing Zeng, Jia Yu, Huangyu Jiang, Linlin Lu, Xiaoxiao Qi, Ying Wang, Ming Hu, Zhongqiu Liu
FVB mice are extensively used in transgenic and pharmacokinetic research. In this study, a validated isotope label-free method of using ultrahigh-performance liquid chromatography (UHPLC)-MS/MS was established for quantifying 24 drug-metabolizing enzymes (DMEs) in FVB mice. The DMEs include cytochrome P450 (CYPs/Cyps), UDP-glucuronsyltransferases (UGTs/Ugts), and sulfotransferases (SULTs/Sults), which are the major phase I and II metabolic enzymes responsible for clearing and detoxifying xenobiotic and endogenous substances...
March 29, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
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