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https://www.readbyqxmd.com/read/29226620/comparative-potency-of-obeticholic-acid-and-natural-bile-acids-on-fxr-in-hepatic-and-intestinal-in%C3%A2-vitro-cell-models
#1
Yuanyuan Zhang, Carl LaCerte, Sanjay Kansra, Jonathan P Jackson, Kenneth R Brouwer, Jeffrey E Edwards
Obeticholic acid (OCA) is a semisynthetic farnesoid X receptor (FXR) agonist, an analogue of chenodeoxycholic acid (CDCA) which is indicated for the treatment of primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA). OCA efficiently inhibits bile acid synthesis and promotes bile acid efflux via activating FXR-mediated mechanisms in a physiologically relevant in vitro cell system, Sandwich-cultured Transporter Certified ™ human primary hepatocytes (SCHH). The study herein evaluated the effects of UDCA alone or in combination with OCA in SCHH...
December 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/29209109/resveratrol-modifies-biliary-secretion-of-cholephilic-compounds-in-sham-operated-and-cholestatic-rats
#2
Eva Dolezelova, Alena Prasnicka, Jolana Cermanova, Alejandro Carazo, Lucie Hyrsova, Milos Hroch, Jaroslav Mokry, Michaela Adamcova, Alena Mrkvicova, Petr Pavek, Stanislav Micuda
AIM: To investigate the effect of resveratrol on biliary secretion of cholephilic compounds in healthy and bile duct-obstructed rats. METHODS: Resveratrol (RSV) or saline were administered to rats by daily oral gavage for 28 d after sham operation or reversible bile duct obstruction (BDO). Bile was collected 24 h after the last gavage during an intravenous bolus dose of the Mdr1/Mrp2 substrate azithromycin. Bile acids, glutathione and azithromycin were measured in bile to quantify their level of biliary secretion...
November 21, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29198707/impaired-vagus-function-in-rats-suppresses-bile-acid-synthesis-in-the-liver-by-disrupting-tight-junctions-and-activating-fxr-fgf15-signaling-in-the-intestine
#3
Fangyu Wang, Zhiqiang Lu, Xue Wang, Youcai Zhang
Bile acids (BAs) circulate between the liver and intestine, and regulate the homeostasis of glucose, lipid, and energy. Recent studies demonstrated an essential role of BAs in neurological diseases, suggesting an interaction between BAs and the nervous system. In the present study, we showed that impaired vagus function in rats induced by vagotomy resulted in an increase in bile flow without causing liver injury. The concentrations of unconjugated and glycine-conjugated BAs were increased in both serum and bile of rats after vagotomy, which was due to impaired tight junctions and thus increased passive absorption of BAs in the intestine...
November 30, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29197246/combined-toxicity-of-endosulfan-and-phenanthrene-mixtures-and-induced-molecular-changes-in-adult-zebrafish-danio-rerio
#4
Kyeongnam Kim, Hwang-Ju Jeon, Sung-Deuk Choi, Daniel C W Tsang, Patryk Oleszczuk, Yong Sik Ok, Hoi-Seon Lee, Sung-Eun Lee
Individual and combined toxicities of endosulfan (ENDO) with phenanthrene (PHE) were evaluated using zebrafish (Danio rerio) adults. The 96-h LC50 values for ENDO and PHE were 4.6 μg L-1 and 920 μg L-1, respectively. To evaluate the mixture toxicity, LC10 and LC50 concentrations were grouped into four combinations as ENDO-LC10 + PHE-LC10, ENDO-LC10 + PHE-LC50, ENDO-LC50 + PHE-LC10, and ENDO-LC50 + PHE-LC50, and their acute toxicities were determined. The combination of LC50-ENDO and LC10-PHE exhibited a synergistic effect...
November 23, 2017: Chemosphere
https://www.readbyqxmd.com/read/29193679/increased-levels-of-27-hydroxycholesterol-induced-by-dietary-cholesterol-in-brain-contribute-to-the-learning-and-memory-impairment-in-rats
#5
Xiaona Zhang, Chenyan Lv, Yu An, Quanri Liu, Hongguo Rong, Lingwei Tao, Ying Wang, Yushan Wang, Rong Xiao
SCOPE: Dietary cholesterol has been shown to play a role in the development of Alzheimer's disease (AD). We have proposed that oxysterol especially 27-hydroxycholesterol (27-OHC) may play a potential role in β-amyloid peptides (Aβ) production and accumulation during AD progression. METHODS AND RESULTS: To investigate the mechanisms of dietary cholesterol and 27-OHC on learning and memory impairment, male Sprague-Dawley rats were fed with cholesterol diet with or without 27-OHC synthetase inhibitor (anastrozole) injection...
November 28, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/29191818/sterol-27-hydroxylase-gene-dosage-and-the-anti-atherosclerotic-effect-of-rifampicin-in-mice
#6
Line Zurkinden, Dmitri Sviridov, Bruno Vogt, Geneviève Escher
Sterol 27-hydroxylase (CYP27A1) catalyzes the hydroxylation of cholesterol to 27-hydroxycholesterol (27-OHC) and regulates cholesterol homeostasis. In Cyp27a1/Apolipoprotein E (ApoE) double knockout (KO) mice fed with western diet (WD), the atherosclerotic phenotype found in ApoE KO mice was reversed. As protective mechanism, up-regulation of Cyp3a11 and Cyp7a1 was proposed. Cyp27a1 heterozygote/ ApoE KO (het) mice, with reduced Cyp27a1expression and normal levels of Cyp7a1 and Cyp3a11 , developed more severe lesions than ApoE KO mice...
November 30, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/29190422/structure-specific-effects-of-short-chain-fatty-acids-on-plasma-cholesterol-concentration-in-male-syrian-hamsters
#7
Yimin Zhao, Jianhui Liu, Wangjun Hao, Hanyue Zhu, Ning Liang, Zouyan He, Ka Ying Ma, Zhen-Yu Chen
Previous studies have shown that short-chain fatty acids (SCFAs) are capable of decreasing plasma cholesterol. However, the relative plasma cholesterol-lowering activity of individual SCFAs and the underlying mechanisms by which SCFAs decrease plasma cholesterol remain largely unknown. The present study was to compare plasma cholesterol-lowering potency of four common SCFAs with 2-5 carbons, and to investigate their interactions with gene expressions of key regulatory factors involved in cholesterol metabolism...
November 30, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29175453/activation-of-ppar%C3%AE-decreases-bile-acids-in-livers-of-female-mice-while-maintaining-bile-flow-and-biliary-bile-acid-excretion
#8
Youcai Zhang, Andrew J Lickteig, Iván L Csanaky, Curtis D Klaassen
Fibrates are hypolipidemic drugs that act as activators of peroxisome proliferator-activated receptor α (PPARα). In both humans and rodents, females were reported to be less responsive to fibrates than males. Previous studies on fibrates and PPARα usually involved male mice, but little has been done in females. The present study aimed to provide the first comprehensive analysis of the effects of clofibrate (CLOF) and PPARα on bile acid (BA) homeostasis in female mice. Study in WT male mice showed that a 4-day CLOF treatment increased liver weight, bile flow, and biliary BA excretion, but decreased total BAs in both serum and liver...
November 22, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29172112/cholesterol-lowering-effects-of-dietary-pomegranate-extract-and-inulin-in-mice-fed-an-obesogenic-diet
#9
Jieping Yang, Song Zhang, Susanne M Henning, Rupo Lee, Mark Hsu, Emma Grojean, Rita Pisegna, Austin Ly, David Heber, Zhaoping Li
BACKGROUND: It has been demonstrated in animal studies that both polyphenol-rich pomegranate extract (PomX) and the polysaccharide inulin, ameliorate metabolic changes induced by a high-fat diet, but little is known about the specific mechanisms. OBJECTIVE: This study evaluated the effect of PomX (0.25%) and inulin (9%) alone or in combination on cholesterol and lipid metabolism in mice. METHODS: Male C57BL/6 J mice were fed high-fat/high-sucrose [HF/HS (32% energy from fat, 25% energy from sucrose)] diets supplemented with PomX (0...
October 16, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/29171472/-cyp7a1-gene-polymorphism-and-the-characteristics-of-dyslipidemias-in-patients-with-nonalcoholic-fatty-liver-disease-concurrent-with-hypothyroidism
#10
D A Zhaldak, O K Melekhovets, V F Orlovskyi
AIM: To investigate the association of the polymorphic variants -204A > C (rs 3808607) in the CYP7A1 gene with the development of dyslipidemias in healthy individuals, in patients with non-alcoholic fatty liver disease (NAFLD) and in those with NAFLD concurrent with hypothyroidism. SUBJECTS AND METHODS: DNA samples and lipidograms were examined in 180 patients, including 60 healthy individuals (Group 1), 60 patients with hypothyroidism concurrent with NAFLD (Group 2), and 60 patients with NAFLD (Group 3)...
2017: Terapevticheskiĭ Arkhiv
https://www.readbyqxmd.com/read/29169169/effects-and-interactions-of-prenatal-ethanol-exposure-a-post-weaning-high-fat-diet-and-gender-on-adult-hypercholesterolemia-occurrence-in-offspring-rats
#11
Yongjian Qi, Hanwen Luo, Shuwei Hu, Yimeng Wu, Jacques Magdalou, Liaobin Chen, Hui Wang
BACKGROUND/AIMS: Prenatal ethanol exposure (PEE) could induce intrauterine programming of hypothalamic-pituitary-adrenal axis-associated neuroendocrine metabolism, resulting in intrauterine growth retardation and susceptibility to adult hypercholesterolemia in offspring. This study aimed to analyse the effects and interactions of PEE, a post-weaning high-fat diet (HFD) and gender on the occurrence of adult hypercholesterolemia in offspring rats. METHODS: Wistar female rats were treated with ethanol (4 g/kg...
November 23, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29159825/modulation-of-the-intestinal-bile-acid-fxr-fgf15-axis-improves-alcoholic-liver-disease-in-mice
#12
Phillipp Hartmann, Katrin Hochrath, Angela Horvath, Peng Chen, Caroline T Seebauer, Cristina Llorente, Lirui Wang, Yazen Alnouti, Derrick E Fouts, Peter Stärkel, Rohit Loomba, Sally Coulter, Christopher Liddle, Ruth T Yu, Lei Ling, Stephen J Rossi, Alex M DePaoli, Michael Downes, Ronald M Evans, David A Brenner, Bernd Schnabl
Alcoholic liver disease is associated with changes in the intestinal microbiota. Functional consequences of alcohol-associated dysbiosis are largely unknown. The aim of this study was to identify a mechanism of how changes in the intestinal microbiota contribute to alcoholic liver disease. Metagenomic sequencing of intestinal contents demonstrated that chronic ethanol feeding in mice is associated with an overrepresentation of bacterial genomic DNA encoding choloylglycine hydrolase, which deconjugates bile acids in the intestine...
November 21, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29155143/obeticholic-acid-raises-ldl-cholesterol-and-reduces-hdl-cholesterol-in-the-diet-induced-nash-din-hamster-model
#13
François Briand, Emmanuel Brousseau, Marjolaine Quinsat, Rémy Burcelin, Thierry Sulpice
The use of rat and mouse models limits the translation to humans for developing novel drugs targeting nonalcoholic steatohepatitis (NASH). Obeticholic acid (OCA) illustrates this limitation since its dyslipidemic effect in humans cannot be observed in these rodents. Conversely, Golden Syrian hamsters have a lipoprotein metabolism mimicking human dyslipidemia since it does express the cholesteryl ester transfer protein (CETP). We therefore developed a Diet-induced NASH (DIN) hamster model and evaluated the impact of OCA...
November 16, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29147129/the-effect-of-exercise-training-on-upregulation-of-molecular-markers-of-bile-acid-metabolism-in-the-liver-of-ovariectomized-rats-fed-a-cholesterol-rich-diet
#14
Zahra Farahnak, Luciane Magri Tomaz, Raynald Bergeron, Natalie Chapados, Jean-Marc Lavoie
BACKGROUND: Small heterodimer partner (SHP) is an important transcriptional factor involved in the regulation of glucose, lipid, and bile acid metabolism in the liver. SHP has been reported to be down-regulated in ovariectomized (Ovx) mice and up-regulated by estrogens suggesting a link between estrogens and SHP. The aim of the present study was to determine the effects of exercise training on SHP and key molecular markers of cholesterol and bile acid homeostasis in Ovx rats under cholesterol feeding...
July 2017: ARYA Atherosclerosis
https://www.readbyqxmd.com/read/29139309/polyphenolic-characterisation-of-plant-mixture-lisosan%C3%A2-reduction-and-its-hypocholesterolaemic-effect-in-high-fat-diet-fed-mice
#15
Rossella Russo, Laura Pucci, Lucia Giorgetti, Július Árvay, Francesco Vizzarri, Vincenzo Longo, Luisa Pozzo
Lisosan® Reduction is a plant mixture produced from powder of fermented Triticum aestivum (Lisosan® G), Desmodium adscendens, Malus domestica, Picrorhiza kurroa and Hordeum vulgare. The aim of this study was to characterise the phenolic profile of Lisosan® Reduction and to evaluate the effects of aqueous extract on mice fed a high fat diet (HFD). Syringic acid, trans sinapic acid and neochlorogenic acid were identified by HPLC-DAD to be the dominant polyphenols of Lisosan® Reduction, followed by vitexin, trans p-coumeric acid and trans ferulic acid...
November 15, 2017: Natural Product Research
https://www.readbyqxmd.com/read/29124333/assessment-of-hepatotoxicity-of-first-line-anti-tuberculosis-drugs-on-wistar-rats
#16
Radhika Sharma, Ramneek Kaur, Manishi Mukesh, Vijay L Sharma
Adverse drug reactions are inevitable risk factors associated with use of modern medicines. First-line anti-tuberculosis drugs contribute to diverse pathological complications, and hepatotoxicity is one of them. This study investigated the effects of anti-TB drugs in combination (rifampicin [RIF] + isoniazid [INH] + pyrazinamide [PZA]) on Wistar rats. Rats were grouped as control group (saline), toxicant group that was given (30.85 mg/kg b.wt., INH + 61.7 mg/kg b.wt., RIF + 132.65 mg/kg b.wt. PZA in dosage extrapolated from dose that is used in human)...
November 9, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/29115933/new-variant-identified-in-major-susceptibility-locus-to-tuberculosis-on-chromosomal-region-8q12-q13-in-moroccan-population-a-case-control-study
#17
Mounia Qrafli, Imane Asekkaj, Jamal Eddine Bourkadi, Rajae El Aouad, Khalid Sadki
BACKGROUND: Tuberculosis (TB) remains a global health problem. Several studies have implicated genetic host factors in predisposing populations to TB disease. In this study, we have selected NSMAF (Neutral Sphingomyelinase Activation Associated Factor) as a candidate gene to evaluate its level of association with TB disease in a Moroccan population for two reasons: first, this gene is located in a major susceptibility locus on chromosomal region 8q12-q13 in the Moroccan population, closely linked to the CYP7A1 gene, which was previously shown to be associated with TB disease; second, NSMAF has an important role in immune system function...
November 7, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/29115200/barley-%C3%AE-glucan-reduces-blood-cholesterol-levels-via-interrupting-bile-acid-metabolism
#18
Yanan Wang, Scott V Harding, Sijo J Thandapilly, Susan M Tosh, Peter J H Jones, Nancy P Ames
Underlying mechanisms responsible for the cholesterol-lowering effect of β-glucan have been proposed, yet have not been fully demonstrated. The primary aim of this study was to determine whether the consumption of barley β-glucan lowers cholesterol by affecting the cholesterol absorption, cholesterol synthesis or bile acid synthesis. In addition, this study was aimed to assess whether the underlying mechanisms are related to cholesterol 7α hydroxylase (CYP7A1) SNP rs3808607 as proposed by us earlier. In a controlled, randomised, cross-over study, participants with mild hypercholesterolaemia (n 30) were randomly assigned to receive breakfast containing 3 g high-molecular weight (HMW), 5 g low-molecular weight (LMW), 3 g LMW barley β-glucan or a control diet, each for 5 weeks...
November 8, 2017: British Journal of Nutrition
https://www.readbyqxmd.com/read/29112762/alteration-of-bile-acid-and-cholesterol-biosynthesis-and-transport-by-perfluorononanoic-acid-pfna-in-mice
#19
Yue Zhang, Youcai Zhang, Curtis D Klaassen, Xingguo Cheng
Perfluorochemicals produce hepatotoxic effects via activation of PPARα and CAR nuclear receptors in animals. Bile formation is one major liver function. But it remains unknown whether perfluorochemicals alter metabolism of bile acids (BAs) in liver. The present study was designed to determine the impact of perfluorononanoic acid (PFNA) on BA and cholesterol homeostasis in mice. A single dose of PFNA (0.1 mmol/kg) was intraperitoneally administered to adult male wild-type (WT), PPARα-null, and CAR-null mice...
November 3, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29108969/dietary-butylated-hydroxytoluene-improves-lipid-metabolism-antioxidant-and-anti-apoptotic-response-of-largemouth-bass-micropterus-salmoides
#20
L L Yu, H H Yu, X F Liang, N Li, X Wang, F H Li, X F Wu, Y H Zheng, M Xue, X F Liang
A 10-week growth trail was conducted to investigate the efficacy and tolerance of dietary butylated hydroxytoluene (BHT) by evaluating inflammation, apoptosis and hepatic disease related to oxidative stress in largemouth bass (Micropterus salmoides). Four experimental diets were prepared with BHT supplement levels of 0 (B0), 150 (B150), 300 (B300) and 1500 (B1500) mg/kg, in which B150 was at the maximum recommended level established by European Union Regulation, and the B300 and B1500 levels were 2 and 10-fold of B150, respectively...
November 7, 2017: Fish & Shellfish Immunology
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