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https://www.readbyqxmd.com/read/28535465/altered-glycometabolism-in-zebrafish-exposed-to-thifluzamide
#1
Yang Yang, Wenxian Liu, Dongzhi Li, Le Qian, Bin Fu, Chengju Wang
Thifluzamide exerts toxic effects to zebrafish and causes liver mitochondrial damage. To better understand the further mechanism, adult zebrafish were exposed to a range of thifluzamide concentrations (0, 0.019, 0.19, and 1.90 mg/L) for 28 days. In response to 1.90 mg/L exposure, liver glycogen significantly increased and blood glucose decreased. The expression of genes related to glycometabolism showed corresponding changes. Genes related to mtDNA replication and transcription and genes participating in mitochondrial complexes showed altered expression, which might lead to the inhibition of the tricarboxylic acid cycle (TCA)...
May 10, 2017: Chemosphere
https://www.readbyqxmd.com/read/28533525/cellular-responses-to-t-2-toxin-and-or-deoxynivalenol-that-induce-cartilage-damage-are-not-specific-to-chondrocytes
#2
Yang Lei, Zhao Guanghui, Wang Xi, Wang Yingting, Lin Xialu, Yu Fangfang, Mary B Goldring, Guo Xiong, Mikko J Lammi
The relationship between T-2 toxin and deoxynivalenol (DON) and the risk of Kashin-Beck disease is still controversial since it is poorly known about their selectivity in cartilage damage. We aimed to compare the cytotoxicity of T-2 toxin and DON on cell lines representative of cell types encountered in vivo, including human chondrocytes (C28/I2), human hepatic epithelial cells (L-02) and human tubular epithelial cells (HK-2). In addition, we determined the distribution of T-2 toxin and DON in Sprague-Dawley (SD) rats after a single dose exposure...
May 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28527664/a-new-hdv-mouse-model-identifies-mitochondrial-antiviral-signaling-protein-mavs-as-a-key-player-in-ifn-%C3%AE-induction
#3
Lester Suárez-Amarán, Carla Usai, Marianna Di Scala, Cristina Godoy, Yi Ni, Mirja Hommel, Laura Palomo, Víctor Segura, Cristina Olagüe, Africa Vales, Alicia Ruiz-Ripa, Maria Buti, Eduardo Salido, Jesús Prieto, Stephan Urban, Francisco Rodríguez-Frias, Rafael Aldabe, Gloria González-Aseguinolaza
BACKGROUND & AIMS: Studying hepatitis delta virus (HDV) and developing new treatments is hampered by the limited availability of small animal models. Here a description of a robust mouse model of HDV infection that mimics several important characteristics of the human disease is presented. METHODS: HDV- and HBV-replication competent genomes were delivered to the mouse liver using adeno-associated viruses (AAV) (AAV-HDV and AAV-HBV). Viral load, antigen expression and genomes were quantified at different time points after AAV injection...
May 17, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28526873/role-of-s-palmitoylation-by-zdhhc13-in-mitochondrial-function-and-metabolism-in-liver
#4
Li-Fen Shen, Yi-Ju Chen, Kai-Ming Liu, Amir N Saleem Haddad, I-Wen Song, Hsiao-Yuh Roan, Li-Ying Chen, Jeffrey J Y Yen, Yu-Ju Chen, Jer-Yuarn Wu, Yuan-Tsong Chen
Palmitoyltransferase (PAT) catalyses protein S-palmitoylation which adds 16-carbon palmitate to specific cysteines and contributes to various biological functions. We previously reported that in mice, deficiency of Zdhhc13, a member of the PAT family, causes severe phenotypes including amyloidosis, alopecia, and osteoporosis. Here, we show that Zdhhc13 deficiency results in abnormal liver function, lipid abnormalities, and hypermetabolism. To elucidate the molecular mechanisms underlying these disease phenotypes, we applied a site-specific quantitative approach integrating an alkylating resin-assisted capture and mass spectrometry-based label-free strategy for studying the liver S-palmitoylome...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28526448/the-catechol-o-methyltransferase-inhibitors-tolcapone-and-entacapone-uncouple-and-inhibit-the-mitochondrial-respiratory-chain-in-heparg-cells
#5
David Grünig, Andrea Felser, Jamal Bouitbir, Stephan Krähenbühl
The catechol-O-methyltransferase inhibitor tolcapone causes hepatotoxicity and mitochondrial damage in animal models. We studied the interaction of tolcapone with mitochondrial respiration in comparison to entacapone in different experimental models. In HepaRG cells (human cell-line), tolcapone decreased the ATP content (estimated IC50 100±15μM) and was cytotoxic (estimated IC50 333±45μM), whereas entacapone caused no cytotoxicity and no ATP depletion up to 200μM. Cytochrome P450 induction did not increase the toxicity of the compounds...
May 16, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28522403/multiplex-autoantibody-detection-for-autoimmune-liver-diseases-and-autoimmune-gastritis
#6
Joris Vanderlocht, Mart van der Cruys, Frans Stals, Liesbeth Bakker-Jonges, Jan Damoiseaux
Autoantibody detection for autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) and autoimmune gastritis (AIG) is traditionally performed by IIF on a combination of tissues. Multiplex line/dot blots (LIA/DIA) offer multiple advantages, i.e. automation, objective reading, no interfering reactivities, no coincidental findings. In the current study we evaluated automated DIA (D-Tek) for detecting autoantibodies related to autoimmune diseases of the gastrointestinal tract. We tested samples of the Dutch EQC program and compared the results with the consensus of the participating labs...
May 15, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/28521615/comprehensive-evaluation-of-usnic-acid-induced-cardiotoxicity-in-rats-by-sequential-cross-omics-analysis
#7
Y Yokouchi, M Imaoka, N Niino, N Kiyosawa, K Kai
Two-week administration of (+)-usnic acid (UA) induces mitochondrial swelling of cardiomyocytes, and toxicogenomic analysis of the heart revealed upregulation of oxidative stress, amino acid limitation, and endoplasmic reticulum stress-related genes in rats. To analyze the pathogenesis, UA was orally administrated to rats for 1, 4, 7, and 14 days, and sequential histopathological, genomic, and metabolomic analyses were performed on the heart, liver, and plasma. As a result, mitochondrial swelling of cardiomyocytes was observed on day 15 preceded by genomic upregulation on days 5 and 8...
January 1, 2017: Toxicologic Pathology
https://www.readbyqxmd.com/read/28515471/clinical-and-molecular-investigation-of-14-japanese-patients-with-complete-tfp-deficiency-a-comparison-with-caucasian-cases
#8
Ryosuke Bo, Kenji Yamada, Hironori Kobayashi, Purevsuren Jamiyan, Yuki Hasegawa, Takeshi Taketani, Seiji Fukuda, Ikue Hata, Yo Niida, Yosuke Shigematsu, Kazumoto Iijima, Seiji Yamaguchi
Mitochondrial trifunctional protein (TFP) deficiency is an inherited metabolic disorder of mitochondrial fatty-acid oxidation. Isolated long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency is often reported in Caucasian countries due to a common mutation. However, the molecular and clinical basis of complete TFP deficiency has not been extensively reported. In this study, 14 Japanese cases (13 families) with complete TFP deficiency, including 9 previously reported cases, were analyzed to clarify the clinical and molecular characteristics of TFP deficiency...
May 18, 2017: Journal of Human Genetics
https://www.readbyqxmd.com/read/28515456/metabolomic-analysis-shows-differential-hepatic-effects-of-t2-and-t3-in-rats-after-short-term-feeding-with-high-fat-diet
#9
Liliana F Iannucci, Federica Cioffi, Rosalba Senese, Fernando Goglia, Antonia Lanni, Paul M Yen, Rohit A Sinha
Nonalcoholic fatty liver disease (NAFLD) is a major health problem worldwide, and is often associated with lipotoxic injury, defective mitochondrial function, and insulin resistance. Thyroid hormones (THs) are important regulators of hepatic lipid metabolism. Among the THs, diiodothyronine (T2) and triiodothyronine (T3) have shown promising results in lowering hepatic fat content in various models of NAFLD. In this study, we used a targeted metabolomics approach to investigate the differential effects of T2 and T3 on the early metabolic adaptation in the livers of rats fed high fat diet (HFD), a period when hepatosteatosis is reversible...
May 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28515388/nitric-oxide-is-critical-for-avoiding-hepatic-lipid-overloading-via-il6-induction-during-liver-regeneration-after-partial-hepatectomy-in-mice
#10
Yue Yu, Miho Tamai, Yoh-Ichi Tagawa
Nitric oxide (NO), generated from L-arginine by three different isoforms of nitric oxide synthase (NOS), is a pleiotropic factor to regulate physiological functions in almost every organ and tissue. Each knockout mouse of iNOS or eNOS has been used to suggest that NO has a crucial role in liver regeneration after partial hepatectomy (PH), for NO may inhibit caspase 3 activity and is required for EGFR signaling. In previous reports, defective mitochondrial β-oxidation was observed in eNOS KO mice, and hepatic steatosis was often correlated to deficient liver regeneration, so we focused on metabolic perspective and hypothesized that NO depletion in PH mice would affect hepatocytic lipolysis and impair hepatocytes proliferation...
May 18, 2017: Experimental Animals
https://www.readbyqxmd.com/read/28514663/fatty-acid-oxidation-in-zebrafish-adipose-tissue-is-promoted-by-1%C3%AE-25-oh-2d3
#11
Xuyan Peng, Guohui Shang, Wenqing Wang, Xiaowen Chen, Qiyong Lou, Gang Zhai, Dongliang Li, Zhenyu Du, Yali Ye, Xia Jin, Jiangyan He, Yi Zhang, Zhan Yin
1α,25(OH)2D3 (vitamin D3) is crucial for mineral homeostasis in mammals, but the precise effects of 1α,25(OH)2D3 in adipose tissue remain to be clarified in vivo. The initial 25-hydroxylation is catalyzed by liver microsomal cytochrome P450 2R1 (CYP2R1), which is conserved in vertebrates. To probe the physiological function(s) of 1α,25(OH)2D3 in teleosts, we generated two independent cyp2r1-deficient zebrafish lines. These mutants exhibit retarded growth and increased obesity, especially in the visceral adipose tissue (VAT)...
May 16, 2017: Cell Reports
https://www.readbyqxmd.com/read/28514599/a-bioenergetics-systems-evaluation-of-ketogenic-diet-liver-effects
#12
Lewis J Hutfles, Heather M Wilkins, Scott J Koppel, Ian W Weidling, J Eva Selfridge, Eephie Tan, John P Thyfault, Chad Slawson, Aron W Fenton, Hao Zhu, Russell H Swerdlow
Ketogenic diets induce hepatocyte fatty acid oxidation and ketone body production. To further evaluate how ketogenic diets affect hepatocyte bioenergetic infrastructure, we analyzed livers from C57Bl/6J male mice maintained for one month on a ketogenic or standard chow diet. Compared to the standard diet, the ketogenic diet increased cytosolic and mitochondrial protein acetylation and also altered protein succinylation patterns. SIRT3 protein decreased while SIRT5 protein increased, and gluconeogenesis, oxidative phosphorylation, and mitochondrial biogenesis pathway proteins were variably and likely strategically altered...
May 17, 2017: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
https://www.readbyqxmd.com/read/28511345/ros-homeostasis-a-key-determinant-in-liver-ischemic-preconditioning
#13
Ignacio Prieto, María Monsalve
Reactive Oxygen Species (ROS) are key mediators of ischemia-reperfusion injury but also required for the induction of the stress response that limits tissue injury and underlies the protection provided by ischemic-preconditioning protocols. Liver steatosis is an important risk factor for liver transplant failure. Liver steatosis is associated with mitochondrial dysfunction and excessive mitochondrial ROS production. Studies aiming at decreasing the sensibility of the steatotic liver to ischemia-reperfusion injury using pre-conditioning protocols, have shown that the steatotic liver has a reduced capacity to respond to these protocols...
May 4, 2017: Redox Biology
https://www.readbyqxmd.com/read/28508193/neutrophil-depletion-improves-diet-induced-non-alcoholic-fatty-liver-disease-in-mice
#14
Rongying Ou, Jia Liu, Mingfen Lv, Jingying Wang, Jinmeng Wang, Li Zhu, Liang Zhao, Yunsheng Xu
PURPOSE: Non-alcoholic fatty liver disease is highly associated with morbidity and mortality in population. Although studies have already demonstrated that the immune response plays a pivotal role in the development of non-alcoholic fatty liver disease, the comprehensive regulation is unclear. Therefore, present study was carried out to investigate the non-alcoholic fatty liver disease development under neutrophil depletion. METHODS: To achieve the aim of the study, C57BL/6 J mice were fed with high fat diet for 6 weeks before treated with neutrophil deplete antibody 1A8 or isotype control (200 μg/ mouse every week) for another 4 weeks...
April 6, 2017: Endocrine
https://www.readbyqxmd.com/read/28506826/an-x-chromosome-linked-mouse-model-ndufa1-s55a-for-systemic-partial-complex-i-deficiency-for-studying-predisposition-to-neurodegeneration-and-other-diseases
#15
Chul Kim, Prasanth Potluri, Ahmed Khalil, Daria Gaut, Meagan McManus, Shannon Compton, Douglas C Wallace, Nagendra Yadava
The respiratory chain Complex I deficiencies are the most common cause of mitochondrial diseases. Complex I biogenesis is controlled by 58 genes and at least 47 of these cause mitochondrial disease in humans. Two of these are X-chromosome linked nuclear (nDNA) genes (NDUFA1 and NDUFB11), and 7 are mitochondrial (mtDNA, MT-ND1-6, -4L) genes, which may be responsible for sex-dependent variation in the presentation of mitochondrial diseases. In this study, we describe an X-chromosome linked mouse model (Ndufa1(S55A)) for systemic partial Complex I deficiency...
May 12, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28506426/heterogeneity-of-fhf1-related-phenotype-novel-case-with-early-onset-severe-attacks-of-apnea-partial-mitochondrial-respiratory-chain-complex-ii-deficiency-neonatal-onset-seizures-without-neurodegeneration
#16
Nathalie Villeneuve, Affef Abidi, Pierre Cacciagli, Cécile Mignon-Ravix, Brigitte Chabrol, Laurent Villard, Mathieu Milh
INTRODUCTION/OBJECTIVES: We report the case of a child prospectively followed in our institution for a severe, neonatal onset epilepsy presenting with severe attacks of apnea that were not initially recognized as seizure since they were not associated with any abnormal movement and since interictal EEG was normal. Recording of attacks using prolonged video-EEG recording allowed to confirm the diagnosis of epileptic seizures. RESULTS: Using whole exome sequencing we found a de novo heterozygous, missense mutation of FHF1 (p...
April 29, 2017: European Journal of Paediatric Neurology: EJPN
https://www.readbyqxmd.com/read/28504722/thyroid-hormone-protects-hepatocytes-from-hbx-induced-carcinogenesis-by-enhancing-mitochondrial-turnover
#17
H-C Chi, S-L Chen, S-L Lin, C-Y Tsai, W-Y Chuang, Y-H Lin, Y-H Huang, M-M Tsai, C-T Yeh, K-H Lin
Infection by hepatitis B virus (HBV) accounts for 50-80% of hepatocellular carcinoma (HCC) development worldwide, in which the HBV-encoded X protein (HBx) has critical role in the induction of carcinogenesis. Several studies have shown that thyroid hormone (TH) suppresses HCC development and protects hepatocytes from HBx-induced damage, thus it is of interest to examine whether TH can protect hepatocytes from HBx-induced carcinogenesis. By treating HBx- transgenic mice with or without TH, we confirmed the protective effects of TH on HBx-induced hepatocarcinogenesis, which was achieved via reduction of reactive oxygen species (ROS) inflicted DNA damage...
May 15, 2017: Oncogene
https://www.readbyqxmd.com/read/28504310/aerobic-capacity-mediates-susceptibility-for-the-transition-from-steatosis-to-steatohepatitis
#18
E Matthew Morris, Colin S McCoin, Julie A Allen, Michelle L Gastecki, Lauren G Koch, Steven L Britton, Justin A Fletcher, Xiarong Fu, Wen-Xing Ding, Shawn C Burgess, R Scott Rector, John P Thyfault
BACKGROUND & AIMS: Low aerobic capacity increases risk for NAFLD and liver-related disease mortality, but mechanisms mediating these effects remain unknown. We recently reported that rats bred for low aerobic capacity (low capacity runner (LCR)) displayed susceptibility to high-fat diet-induced steatosis in association with reduced hepatic mitochondrial fatty acid oxidation (FAO) and respiratory capacity compared to high aerobic capacity (high capacity runners (HCR)) rats. Here we tested the impact of aerobic capacity on susceptibility for progressive liver disease following a 16 week 'western diet' high in fat (45% kcal), cholesterol (1% w w(-1) ), and sucrose (15% kcal)...
May 15, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28503408/trifluoperazine-inhibits-acetaminophen-induced-hepatotoxicity-and-hepatic-reactive-nitrogen-formation-in-mice-and-in-freshly-isolated-hepatocytes
#19
Sudip Banerjee, Stepan B Melnyk, Kimberly J Krager, Nukhet Aykin-Burns, Sandra S McCullough, Laura P James, Jack A Hinson
The hepatotoxicity of acetaminophen (APAP) occurs by initial metabolism to N-acetyl-p-benzoquinone imine which depletes GSH and forms APAP-protein adducts. Subsequently, the reactive nitrogen species peroxynitrite is formed from nitric oxide (NO) and superoxide leading to 3-nitrotyrosine in proteins. Toxicity occurs with inhibited mitochondrial function. We previously reported that in hepatocytes the nNOS (NOS1) inhibitor NANT inhibited APAP toxicity, reactive nitrogen and oxygen species formation, and mitochondrial dysfunction...
2017: Toxicology Reports
https://www.readbyqxmd.com/read/28502921/umbilical-cord-mscs-reverse-d-galactose-induced-hepatic-mitochondrial-dysfunction-via-activation-of-nrf2-ho-1-pathway
#20
Weihong Yan, Dong Li, Tong Chen, Guiying Tian, Panpan Zhou, Xiuli Ju
Mitochondria are the central hubs for cellular bioenergetics and are crucial to cell survival. It is well accepted that compromised mitochondrial function is linked with hepatocytes injury and contribute to progression of liver diseases. Despite the therapeutic potential of mesenchymal stem cells (MSCs) transplantation on hepatic disorders have been extensively investigated, the effects of MSCs on mitochondrial function in liver injury models remain unknown. Here we investigated the effects of treatment with umbilical cord (UC) MSC in a rat model of D-Gal induced liver injury, characterized by organ damage, oxidative stress and mitochondrial dysfunction...
May 13, 2017: Biological & Pharmaceutical Bulletin
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