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https://www.readbyqxmd.com/read/29452137/aryl-hydrocarbon-receptor-ahr-mediated-short-term-effects-of-2-3-7-8-tetrachlorodibenzo-p-dioxin-tcdd-on-bile-acid-homeostasis-in-wild-type-and-ahr-null-mice
#1
Iván L Csanaky, Andrew J Lickteig, Curtis D Klaassen
The effects of the most potent aryl hydrocarbon receptor (AhR) agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on bile acid (BA) homeostasis was examined in male and female wild-type and AhR-null mice shortly after 4-day exposure, rather than at a later time when secondary non-AhR dependent effects are more likely to occur. TCDD had similar effects on BA homeostasis in male and female mice. TCDD decreased the concentration of total-(Σ) BAs in liver by approximately 50% (all major BA categories except for the non-6,12-OH BAs), without decreasing the expression of the rate limiting BA synthetic enzyme (Cyp7a1) or altering the major BA regulatory pathways (FXR) in liver and intestine...
February 13, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29438852/transcriptome-analysis-to-assess-the-cholestatic-hepatotoxicity-induced-by-polygoni-multiflori-radix-up-regulation-of-key-enzymes-of-cholesterol-and-bile-acid-biosynthesis
#2
Li-Long Jiang, Dong-Sheng Zhao, Ya-Xi Fan, Qiong Yu, Yi-Sheng Lai, Ping Li, Hui-Jun Li
Polygoni Multiflori Radix (PMR) has been commonly used as a tonic in China for centuries. However, PMR-associated hepatotoxicity is becoming a safety issue. Cholestasis often occurs in PMR-induced hepatotoxicity in clinical medicine, but the exact mechanism is not completely understood. An RNA-Seq method was employed, in the present study, to explore the molecular mechanism of cholestatic liver injury induced by PMR, characterized by the hepatic transcriptional response in rats exposed to 1 and 20 g/kg PMR for 90 days...
February 10, 2018: Journal of Proteomics
https://www.readbyqxmd.com/read/29432567/bile-acid-sequestration-by-cholestyramine-mitigates-fgfr4-inhibition-induced-alt-elevation
#3
Heiko S Schadt, Armin Wolf, Joerg Andreas Mahl, Kuno Wuersch, Philippe Couttet, Marianne Schwald, Audrey Fischer, Mathilde Lienard, Corinne Emotte, Chi-Hse Teng, Elizabeth Skuba, Terrilyn A Richardson, Luigi Manenti, Andreas Weiss, Diana Graus Porta, Robin A Fairhurst, Gerd A Kullak-Ublick, Salah-Dine Chibout, Francois Pognan, William Kluwe, Jacqueline Kinyamu-Akunda
The FGF19-FGFR4-βKlotho (KLB) pathway plays an important role in the regulation of bile acid (BA) homeostasis. Aberrant activation of this pathway has been described in the development and progression of a subset of liver cancers including hepatocellular carcinoma (HCC), establishing FGFR4 as an attractive therapeutic target for such solid tumors. FGF401 is a highly selective FGFR4 kinase inhibitor being developed for HCC, currently in Phase I/II clinical studies. In preclinical studies in mice and dogs, oral administration of FGF401 led to induction of Cyp7a1, elevation of its peripheral marker 7alpha-hydroxy-4-cholesten-3-one (C4), increased BA pool size, decreased serum cholesterol and diarrhea in dogs...
February 8, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29427579/protective-effects-of-yangonin-from-an-edible-botanical-kava-against-lithocholic-acid-induced-cholestasis-and-hepatotoxicity
#4
Yulong Kong, Xiaoguang Gao, Changyuan Wang, Chenqing Ning, Kexin Liu, Zhihao Liu, Huijun Sun, Xiaodong Ma, Pengyuan Sun, Qiang Meng
Accumulation of toxic bile acids in liver could cause cholestasis and liver injury. The purpose of the current study is to evaluate the hepatoprotective effect of yangonin, a product isolated from an edible botanical Kava against lithocholic acid (LCA)-induced cholestasis, and further to elucidate the involvement of farnesoid X receptor (FXR) in the anticholestatic effect using in vivo and in vitro experiments. The cholestatic liver injury model was established by intraperitoneal injections of LCA in C57BL/6 mice...
February 7, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29425660/cranberry-anthocyanin-as-an-herbal-medicine-lowers-plasma-cholesterol-by-increasing-excretion-of-fecal-sterols
#5
Lijun Wang, Hanyue Zhu, Yimin Zhao, Rui Jiao, Lin Lei, Jingnan Chen, Xiaobo Wang, Zhengnan Zhang, Yu Huang, Tiejie Wang, Zhen-Yu Chen
BACKGROUND: Interest in using herbal medicines to treat the hypercholesterolemia is increasing. Cranberry extract could decrease plasma cholesterol, however, the active ingredients and the underlying mechanisms remain largely unknown. HYPOTHESIS: The present study was to test the hypothesis that cranberry anthocyanins (CrA) were at least one of the active ingredients responsible for the cholesterol-lowering activity of cranberry fruits via a mechanism of increasing fecal sterol excretion...
January 1, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29409992/the-expression-profiling-and-ontology-analysis-of-non-coding-rnas-in-dexamethasone-induced-steatosis-in-hepatoma-cell
#6
Fengqiong Liu, Ruijie Gong, Xiaofei Lv, Huangyuan Li
Increasing amounts of evidence have indicated that non-coding RNAs (ncRNAs) have important regulatory potential in various biological processes. However, the contribution of ncRNAs, especially long non-coding RNAs (lncRNAs) to drug induced steatosis remain largely unknown. The aim of this study is to investigate miRNA, lncRNA and mRNA expression profiles and their potential roles in the process of drug induced steatosis. Microarray expression profiles of miRNAs, lncRNAs and mRNAs were determined in dexamethasone treated HepG2 cell as well as control cell...
January 31, 2018: Gene
https://www.readbyqxmd.com/read/29404516/deficiency-of-cholesterol-7%C3%AE-hydroxylase-in-bile-acid-synthesis-exacerbates-alcohol-induced-liver-injury-in-mice
#7
Ajay C Donepudi, Jessica M Ferrell, Shannon Boehme, Hueng-Sik Choi, John Y L Chiang
Alcoholic fatty liver disease (AFLD) is a major risk factor for cirrhosis-associated liver diseases. Studies demonstrate that alcohol increases serum bile acids in humans and rodents. AFLD has been linked to cholestasis, although the physiologic relevance of increased bile acids in AFLD and the underlying mechanism of increasing the bile acid pool by alcohol feeding are still unclear. In this study, we used mouse models either deficient of or overexpressing cholesterol 7α-hydroxylase (Cyp7a1), the rate-limiting and key regulatory enzyme in bile acid synthesis, to study the effect of alcohol drinking in liver metabolism and inflammation...
January 2018: Hepatology Communications
https://www.readbyqxmd.com/read/29382564/diabetic-cognitive-dysfunction-is-associated-with-increased-bile-acids-in-liver-and-activation-of-bile-acid-signaling-in-intestine
#8
Xue Wang, Fangyu Wang, Yidan Zhang, Hui Xiong, Yanjun Zhang, Pengwei Zhuang, Youcai Zhang
Impaired regulation of bile acid (BA) homeostasis has been suggested to be associated with adverse metabolic consequences. However, whether BA homeostasis is altered in diabetes-induced cognitive dysfunction (DCD) remains unknown. In the present study, mice were divided into four groups, namely normal control (NC) group, high-fat diet (HFD) group, diabetes without cognitive dysfunction (unDCD) group, and DCD group. Compared to HFD mice, the concentration of total BAs in liver was higher in unDCD and DCD mice, due to increased intestinal BA absorption...
January 27, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29381405/the-influences-of-cholecystectomy-on-the-circadian-rhythms-of-bile-acids-as-well-as-the-enterohepatic-transporters-and-enzymes-systems-in-mice
#9
Fan Zhang, Yingting Duan, Lili Xi, Mengmeng Wei, Axi Shi, Yan Zhou, Yuhui Wei, Xinan Wu
Bile acids (BAs), the most important endogenous and signaling molecules regulate the target transporters and enzymes at transcriptional level, participate in a wide variety of processes throughout the entire gastrointestinal tract to orchestrate homeostasis in vivo. BAs and their metabolism and transportation appear to follow the clear circadian rhythms, and they are recently proposed also as the potential chronobiological signals that can affect the molecular clock mechanism. Cholecystectomy are believed to affect the circadian rhythms of BAs and the relevant enterohepatic transporters and enzymes systems and their regulatory signaling pathways, for the reason that the circadian cycle of gallbladder filling and emptying play a pivotal role in controlling the flow of bile into the intestine and the enterohepatic circulation of BAs...
January 30, 2018: Chronobiology International
https://www.readbyqxmd.com/read/29365971/the-correlation-between-polimorphism-of-cyp7a1-gene-and-glycated-hemoglobin-in-hypertensive-patients-with-type-2-diabetes-mellitus
#10
Nadiia Demikhova, Olga Chernatska, Olga Smiianova, Lyudmyla Vynnychenko
No abstract text is available yet for this article.
August 2017: Atherosclerosis
https://www.readbyqxmd.com/read/29365813/genetic-variants-in-cyp7a1-and-risk-of-myocardial-infarction-and-symptomatic-gallstone-disease
#11
Faiza Qayyum, Bo Lauridsen, Ruth Frikke-Schmidt, Børge Nordestgaard, Anne Tybjærg-Hansen
No abstract text is available yet for this article.
August 2017: Atherosclerosis
https://www.readbyqxmd.com/read/29363499/metabolic-profiling-of-the-novel-hif2%C3%AE-inhibitor-pt2385-in-vivo-and-in-vitro
#12
Cen Xie, Xiaoxia Gao, Dongxu Sun, Youbo Zhang, Kristopher W Krausz, Xuemei Qin, Frank Gonzalez
PT2385 is a first-in-class, selective small molecule inhibitor of hypoxia inducible factor-2α (HIF-2α) developed for the treatment of advanced clear cell renal cell carcinoma. Preclinical results demonstrated that PT2385 has potent anti-tumor efficacy in mouse xenograft models of kidney cancer. It also has activity toward metabolic disease in a mouse model. However, no metabolism data is currently publicly available. It is of great importance to characterize the metabolism of PT2385 and identify its effect on systemic homeostasis in mice...
January 23, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29360226/modulation-of-transport-and-metabolism-of-bile-acids-and-bilirubin-by-chlorogenic-acid-against-hepatotoxity-and-cholestasis-in-bile-duct-ligation-rats-involvement-of-sirt1-mediated-deacetylation-of-fxr-and-pgc-1%C3%AE
#13
Lili Zhu, Lei Wang, Fei Cao, Peng Liu, Haidong Bao, Yumei Yan, Xin Dong, Dong Wang, Zhongyu Wang, Peng Gong
PURPOSE: To investigate the effect and potential mechanism of chlorogenic acid (CA) on liver injury induced by cholestasis in a rat model of bile duct ligation (BDL). METHODS: Rats received vehicle or CA (20, 50, or 100 mg/kg/d) orally for 3 days. On the 4th day, the rats underwent sham or BDL surgery, and were orally administrated vehicle or CA for 3 or 7 days. mRNA and protein expression levels were evaluated by qRT-PCR and western blot. RESULTS: After BDL, plasma levels of ALT, AST, total bilirubin (TBIL), and total bile acids (TBA) were increased and typical pathological changes were observed in liver morphology...
January 23, 2018: Journal of Hepato-biliary-pancreatic Sciences
https://www.readbyqxmd.com/read/29355561/ameliorating-effects-of-d-47-a-newly-developed-compound-on-lipid-metabolism-in-an-animal-model-of-familial-hypercholesterolemia-whhlmi-rabbits
#14
Shohei Tamura, Yui Koike, Hiroaki Takeda, Tomonari Koike, Yoshihiro Izumi, Ryosuke Nagasaka, Tetsuto Tsunoda, Motoo Tori, Kazuo Ogawa, Takeshi Bamba, Masashi Shiomi
Improvements induced in lipid metabolism in the liver by D-47, a newly developed compound, were examined herein. WHHLMI rabbits, an animal model of hypercholesterolemia and coronary atherosclerosis, was fed D-47-supplemented chow for 5 weeks at a dose of 30mg/kg. Lipid concentration were assayed using enzymatic methods. Plasma lipoproteins were fractionated with an ultracentrifuge. mRNA expression was analyzed with real-time PCR. Lipidome analyses of lipoproteins were performed using supercritical fluid chromatography mass spectrometry...
January 16, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29325849/coagonist-of-glp-1-and-glucagon-decreases-liver-inflammation-and-atherosclerosis-in-dyslipidemic-condition
#15
Vishal Patel, Amit Joharapurkar, Samadhan Kshirsagar, Brijesh Sutariya, Maulik Patel, Dhreerendra Pandey, Hiren Patel, Ramchandra Ranvir, Shekhar Kadam, Dipam Patel, Rajesh Bahekar, Mukul Jain
Dyslipidemia enhances progression of atherosclerosis. Coagonist of GLP-1 and glucagon are under clinical investigation for the treatment of obesity and diabetes. Earlier, we have observed that coagonist reduced circulating and hepatic lipids, independent of its anorexic effects. Here, we investigated the role of coagonist of GLP-1 and glucagon receptors in complications of diet-induced dyslipidemia in hamsters and humanized double transgenic mice. Hamsters fed on high fat high cholesterol diet were treated for 8 weeks with coagonist of GLP-1 and glucagon receptors (75 and 150 μg/kg)...
January 8, 2018: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29313544/dietary-supplementation-of-defatted-kenaf-hibiscus-cannabinus-l-seed-meal-and-its-phenolics-saponins-rich-extract-effectively-attenuates-diet-induced-hypercholesterolemia-in-rats
#16
Kim Wei Chan, Maznah Ismail, Norhaizan Mohd Esa, Mustapha Umar Imam, Der Jiun Ooi, Nicholas M H Khong
Kenaf is one of the important commercial fiber crops worldwide and defatted kenaf seed meal (DKSM) is a secondary by-product from the kenaf industry. Thus, efforts to turn this low-cost agricultural waste into value-added functional food ingredients will definitely bring advantageous impacts to the community health, environment and economy. The present study was aimed to investigate the cardioprotective properties of DKSM and its phenolics-saponins rich extract (PSRE) in diet-induced hypercholesterolemic rat model...
January 9, 2018: Food & Function
https://www.readbyqxmd.com/read/29286073/proteasome-inhibition-protects-against-diet-induced-gallstone-formation-through-modulation-of-cholesterol-and-bile-acid-homeostasis
#17
Eun-Ji Lee, Min Hee Kim, Ye-Ryung Kim, Joo-Won Park, Woo-Jae Park
Gallstone disease is one of the most prevalent and costly gastrointestinal disorders worldwide. Gallstones are formed in the biliary system by cholesterol secretions in bile, which result from excess cholesterol, a deficiency in bile salts or a combination of the two. The present study examined the effects of proteasome inhibition on gallstone formation using the proteasome inhibitors bortezomib (BT) and carfilzomib (CF). C57BL/6J mice were fed a lithogenic diet to generate gallstones and injected with BT or CF for 12 weeks...
December 15, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29275178/central-administration-of-coagonist-of-glp-1-and-glucagon-receptors-improves-dyslipidemia
#18
Vishal Patel, Amit Joharapurkar, Samadhan Kshirsagar, Brijesh Sutariya, Maulik Patel, Hiren Patel, Dheerendra Pandey, Dipam Patel, Rajesh Bahekar, Mukul Jain
Coagonists of Glucagon-like peptide-1 (GLP-1) and glucagon receptors are under clinical investigation for treatment of obesity associated with diabetes. In addition to their role in glucose homeostasis, GLP-1 and glucagon modulate lipid metabolism. In this study, we have investigated the role of central GLP-1 receptor (GLP-1R) and glucagon receptor (GCGR) activation in regulation of lipid metabolism in cholesterol-fed hamsters. Hamsters were treated with coagonist alone (0.3 μg) or in combination with either GLP-1R antagonist (0...
December 21, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29274033/supplementation-with-an-insoluble-fiber-obtained-from-carob-pod-ceratonia-siliqua-l-rich-in-polyphenols-prevents-dyslipidemia-in-rabbits-through-sirt1-pgc-1%C3%AE-pathway
#19
María Valero-Muñoz, Sandra Ballesteros, Baltasar Ruiz-Roso, Lourdes Pérez-Olleros, Beatriz Martín-Fernández, Vicente Lahera, Natalia de Las Heras
PURPOSE: To investigate the mechanism implicated in the effect of an insoluble fiber (obtained from carob pod) rich in polyphenols (IFCP) in lipid metabolism in the liver. METHODS: Male New Zealand rabbits were fed with the following diets for 8 weeks: control diet (CT group), dyslipidemic diet supplemented with 0.5% cholesterol + 14% coconut oil (DL group) and dyslipidemic diet containing 0.5% cholesterol + 14% coconut oil plus 3% IFCP (DL + IFCP group)...
December 22, 2017: European Journal of Nutrition
https://www.readbyqxmd.com/read/29243851/alterations-in-gene-expression-in-vitamin-d-deficiency-down-regulation-of-liver-cyp7a1-and-renal-oat3-in-mice
#20
Holly P Quach, Keumhan Noh, Stacie Y Hoi, Adrie Bruinsma, Geny M M Groothuis, Albert P Li, Edwin C Y Chow, K Sandy Pang
The vitamin D-deficient model, established in C57BL/6 mouse after 8-week feeding of vitamin D-deficient diets in absence or presence of added calcium, was found associated with elevated levels of plasma parathyroid hormone (PTH) and plasma and liver cholesterol, and reduction in cholesterol 7α-hydroxylase (Cyp7a1, rate-limiting enzyme for cholesterol metabolism) and renal Oat3 mRNA/protein expression levels. There was, however, no change in plasma calcium and phosphate levels. Appraisal of the liver revealed up-regulation of mRNA expressions of the small heterodimer partner (Shp) and attenuation of Cyp7a1, which contributed to hypercholesterolemia in vitamin D-deficiency...
December 15, 2017: Biopharmaceutics & Drug Disposition
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