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Drug induced liver disease

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https://www.readbyqxmd.com/read/28203489/effects-of-anti-repulsive-guidance-molecule-c-rgmc-hemojuvelin-antibody-on-hepcidin-and-iron-in-mouse-liver-and-tumor-xenografts
#1
S V Torti, E Lemler, B K Mueller, A Popp, F M Torti
OBJECTIVE: Hepcidin is a peptide hormone produced by the liver that regulates systemic iron homeostasis. Hepcidin is also synthesized by tumors, where it contributes to tumor growth by increasing the tumoral retention of iron. Targeted reduction of hepcidin may therefore be useful in reducing tumor growth. H5F9-AM8 is an antibody in preclinical development for the anemia of chronic disease that reduces hepcidin synthesis by binding to RGMc, a co-receptor involved in the transcriptional induction of hepcidin by BMP6...
November 2016: Clinical & Experimental Pharmacology
https://www.readbyqxmd.com/read/28195343/galectin-9-diverse-roles-in-hepatic-immune-homeostasis-and-inflammation
#2
REVIEW
Lucy Golden-Mason, Hugo R Rosen
Glycan-binding proteins which include galectins are involved at all stages of immunity and inflammation, ranging from initiation through resolution. Galectin-9 (Gal-9) is highly expressed in the liver and has a wide variety of biological functions in innate and adaptive immunity that are instrumental in the maintenance of hepatic homeostasis. In the setting of viral hepatitis, increased expression of Gal-9 drives the expansion of regulatory T cells and contraction of effector T cells, thereby favoring viral persistence...
February 13, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28192881/stem-cell-biomaterials-and-growth-factors-therapy-for-hepatocellular-carcinoma
#3
REVIEW
Soleiman Jaferian, Maryam Soleymaninejad, Babak Negahdari, Ali Eatemadi
Hepatocellular carcinoma is an antecedent of liver illnesses, including viral hepatitis, alcohol abuse, or metabolic disease. Transforming growth factor-Beta (TGF-b) plays an important role in creating a favorable microenvironment for tumor cell growth via two major mechanisms: an intrinsic activity as an autocrine growth factor and an extrinsic activity by inducing microenvironment changes. Recently stem cell therapy as also been a promising and potential treatment for liver cancer and in addition signaling pathways like GF/GFR systems, SDF-1α/CXC4 ligand receptor interaction and PI3K/Akt signaling, and cytokines has been identified to regulate cell fate decisions, and can be utilized to positively influence cell therapy outcomes...
February 8, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28192119/leflunomide-induces-nad-p-h-quinone-dehydrogenase-1-enzyme-via-the-aryl-hydrocarbon-receptor-in-neonatal-mice
#4
Amrit Kumar Shrestha, Ananddeep Patel, Renuka T Menon, Weiwu Jiang, Lihua Wang, Bhagavatula Moorthy, Binoy Shivanna
Aryl hydrocarbon receptor (AhR) has been increasingly recognized to play a crucial role in normal physiological homeostasis. Additionally, disrupted AhR signaling leads to several pathological states in the lung and liver. AhR activation transcriptionally induces detoxifying enzymes such as cytochrome P450 (CYP) 1A and NAD(P)H quinone dehydrogenase 1 (NQO1). The toxicity profiles of the classical AhR ligands such as 3-methylcholanthrene and dioxins limit their use as a therapeutic agent in humans. Hence, there is a need to identify nontoxic AhR ligands to develop AhR as a clinically relevant druggable target...
February 10, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28187366/a-combination-of-dietary-n-3-fatty-acids-and-a-cyclooxygenase-1-inhibitor-attenuates-nonalcoholic-fatty-liver-disease-in-mice
#5
Viswanathan Saraswathi, Curtis Perriotte-Olson, Murali Ganesan, Cyrus V Desouza, Yazen Alnouti, Michael J Duryee, Geoffrey M Thiele, Tara M Nordgren, Dahn L Clemens
We sought to determine whether a combination of purified n-3 fatty acids (n-3) and SC-560 (SC), a cyclooxygenase-1-specific inhibitor, is effective in ameliorating nonalcoholic fatty liver disease in obesity. Female wild-type mice were fed a high-fat and high-cholesterol diet (HF) supplemented with n-3 in the presence or absence of SC. Mice treated with SC alone exhibited no change in liver lipids, whereas n-3-fed mice tended to have lower hepatic lipids. Mice given n-3+SC had significantly lower liver lipids compared with HF controls indicating enhanced lipid clearance...
January 27, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28186991/c-terminal-truncated-hepatitis-b-virus-x-protein-regulates-tumorigenicity-self-renewal-and-drug-resistance-via-stat3-nanog-signaling-pathway
#6
Rachel Hiu Ha Ching, Karen Man Fong Sze, Eunice Yuen Ting Lau, Yung-Tuen Chiu, Joyce Man Fong Lee, Irene Oi Lin Ng, Terence Kin Wah Lee
Hepatitis B virus (HBV) is a major risk factor of chronic liver disease and hepatocellular carcinoma (HCC). Random integration of HBV DNA into the host genome is frequent in HCC leading to truncation of the HBV DNA, particularly at the C-terminal end of the HBV X protein (HBx). C-terminally truncated HBx (HBx-ΔC) has been implicated in playing a pro-oncogenic role in hepatocarcinogenesis. However, the mechanism whereby HBx-ΔC1 contributes to hepatocarcinogenesis remains unclear. In this study, we investigated the functional role of HBx-ΔC1 in regulating liver cancer stem cell (CSC) properties...
February 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28184367/novel-immunotherapies-for-autoimmune-hepatitis
#7
REVIEW
Shamir Cassim, Marc Bilodeau, Catherine Vincent, Pascal Lapierre
Autoimmune hepatitis (AIH) is a multifactorial autoimmune disease of unknown pathogenesis, characterized by a loss of immunological tolerance against liver autoantigens resulting in the progressive destruction of the hepatic parenchyma. Current treatments are based on non-specific immunosuppressive drugs. Although tremendous progress has been made using specific biological agents in other inflammatory diseases, progress has been slow to come for AIH patients. While current treatments are successful in the majority of patients, treatment discontinuation is difficult to achieve, and relapses are frequent...
2017: Frontiers in Pediatrics
https://www.readbyqxmd.com/read/28179883/new-microrna-biomarkers-for-drug-induced-steatosis-and-their-potential-to-predict-the-contribution-of-drugs-to-non-alcoholic-fatty-liver-disease
#8
Mireia López-Riera, Isabel Conde, Laia Tolosa, Ángela Zaragoza, José V Castell, María J Gómez-Lechón, Ramiro Jover
Background and Aims: Drug-induced steatosis is a major reason for drug failure in clinical trials and post-marketing withdrawal; and therefore, predictive biomarkers are essential. These could be particularly relevant in non-alcoholic fatty liver disease (NAFLD), where most patients show features of the metabolic syndrome and are prescribed with combined chronic therapies, which can contribute to fatty liver. However, specific biomarkers to assess the contribution of drugs to NAFLD are lacking. We aimed to find microRNAs (miRNAs) responsive to steatotic drugs and to investigate if they could become circulating biomarkers for drug-induced steatosis...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28176894/autoimmune-hepatitis-current-challenges-and-future-prospects
#9
REVIEW
Yoshio Aizawa, Atsushi Hokari
Autoimmune hepatitis (AIH) is a chronic progressive liver disease characterized by high levels of aminotransferases and autoantibodies, hypergammaglobulinemia, and interface hepatitis. AIH affects all races and all ages worldwide, regardless of sex, although a preponderance of females is a constant finding. The etiology of AIH has not been completely elucidated, but immunogenetic background and environmental parameters may contribute to its development. The most important genetic factor is human leukocyte antigens (HLAs), especially HLA-DR, whereas the role of environmental factors is not completely understood...
2017: Clinical and Experimental Gastroenterology
https://www.readbyqxmd.com/read/28174625/sex-and-age-differences-in-the-expression-of-liver-micrornas-during-the-life-span-of-f344-rats
#10
Joshua C Kwekel, Vikrant Vijay, Tao Han, Carrie L Moland, Varsha G Desai, James C Fuscoe
BACKGROUND: Physiological factors such as age and sex have been shown to be risk factors for adverse effects in the liver, including liver diseases and drug-induced liver injury. Previously, we have reported age- and sex-related significant differences in hepatic basal gene expression in rats during the life span that may be related to susceptibility to such adverse effects. However, the underlying mechanisms of the gene expression changes were not fully understood. In recent years, increasing evidence for epigenetic mechanisms of gene regulation has fueled interest in the role of microRNAs (miRNAs) in toxicogenomics and biomarker discovery...
2017: Biology of Sex Differences
https://www.readbyqxmd.com/read/28169366/phytosterol-esters-attenuate-hepatic-steatosis-in-rats-with-non-alcoholic-fatty-liver-disease-rats-fed-a-high-fat-diet
#11
Lihua Song, Dan Qu, Qing Zhang, Jing Jiang, Haiyue Zhou, Rui Jiang, Yating Li, Yao Zhang, Hongli Yan
Given the adverse effects of drugs used for NAFLD treatment, identifying novel and effective natural compound to prevent NAFLD is urgently needed. In the present study, the effects of phytosterol esters (PSEs) on NAFLD were explored. Adult SD rats were randomized into five groups: normal chow diet (NC), high-fat diet (HF), low-, medium- and high-dose PSE treatment plus high-fat diet groups (PSEL, PSEM, and PSEH). Our results showed that the levels of LDL-C in the PSEL group and hepatic TG, TC, and FFA in the three PSEs groups were significantly decreased...
February 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28167864/ezetimibe-reduces-cholesterol-content-and-nf-kappab-activation-in-liver-but-not-in-intestinal-tissue-in-guinea-pigs
#12
Peter Fraunberger, Elisabeth Gröne, Hermann-Josef Gröne, Heinz Drexel, Autar K Walli
BACKGROUND: Statins (HMG CoA reductase inhibitors), in addition to reducing circulating cholesterol and incidence of coronary heart disease, also have pleiotropic, anti-inflammatory effects. Patients with chronic liver diseases, non-alcoholic fatty liver disease (NAFLD) or hepatitis C are often excluded from statin therapy because of adverse effects in a small cohort of patients despite increased cardiovascular risk cholesterol. Ezetimibe, which inhibits cholesterol absorption by inhibition of Niemann-Pick C1 like 1 (NPC1L1) protein in the brush border of intestinal cells, has been suggested as a new therapeutic option in these patients...
2017: Journal of Inflammation
https://www.readbyqxmd.com/read/28163821/the-role-of-cyp2e1-in-the-drug-metabolism-or-bioactivation-in-the-brain
#13
REVIEW
W A García-Suástegui, L A Ramos-Chávez, M Rubio-Osornio, M Calvillo-Velasco, J A Atzin-Méndez, J Guevara, D Silva-Adaya
Organisms have metabolic pathways that are responsible for removing toxic agents. We always associate the liver as the major organ responsible for detoxification of the body; however this process occurs in many tissues. In the same way, as in the liver, the brain expresses metabolic pathways associated with the elimination of xenobiotics. Besides the detoxifying role of CYP2E1 for compounds such as electrophilic agents, reactive oxygen species, free radical products, and the bioactivation of xenobiotics, CYP2E1 is also related in several diseases and pathophysiological conditions...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28161910/associations-of-gender-and-a-proxy-of-female-menopausal-status-with-histological-features-of-drug-induced-liver-injury
#14
Ayako Suzuki, Huiman Barnhart, Jiezhun Gu, Herbert L Bonkovsky, Hans L Tillmann, Robert J Fontana, David E Kleiner
Gender and menopause may contribute to type and severity of drug-induced liver injury (DILI) by influencing host responses to injury. The aim of this study was to assess the associations of gender and female age 50 [a proxy of menopause] with histologic features of liver injury in 212 adults enrolled in the Drug-Induced Liver Injury Network (DILIN) registry METHODS: All participants had a causality score of at least 'probable', a liver biopsy within 30 days of DILI onset, and no prior chronic liver disease...
February 5, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28155845/design-and-fabrication-of-a-scalable-liver-lobule-on-a-chip-microphysiological-platform
#15
Amin A Banaeiyan, Jannick Theobald, Jurgita Paukštyte, Stefan Wölfl, Caroline B Adiels, Mattias Goksör
The design and fabrication of a very large-scale liver-lobule (VLSLL)-on-a-chip device, providing a microphysiological niche for hepatocytes, is described. The device consists of an integrated network of liver-lobule-like hexagonal tissue-culture chambers constructed in a hybrid layout with a separate seed-feed network. As a key feature, each chamber contains a central outlet mimicking the central vein of a liver lobule. Separating chamber walls located between the culture area and feed network protects cells from the shear force of the convective flow...
February 3, 2017: Biofabrication
https://www.readbyqxmd.com/read/28153389/gold-nanoparticles-ameliorate-acetaminophen-induced-hepato-renal-injury-in-rats
#16
Mohd Salim Reshi, Sadhana Shrivastava, Amita Jaswal, Neelu Sinha, Chhavi Uthra, Sangeeta Shukla
Valuable effects of gold particles have been reported and used in complementary medicine for decades. The aim of this study was to evaluate the therapeutic efficacy of gold nanoparticles (AuNPs) against acetaminophen (APAP) induced toxicity. Albino rats were administered APAP at a dose of 2g/kg p.o. once only. After 24h of APAP intoxication, animals were treated with three different doses of AuNPs (50μg/kg, 100μg/kg, 150μg/kg) orally or silymarin at a dose of 50mg/kg p.o., once only. Animals of all the groups were sacrificed after 24h of last treatment...
January 30, 2017: Experimental and Toxicologic Pathology: Official Journal of the Gesellschaft Für Toxikologische Pathologie
https://www.readbyqxmd.com/read/28146130/effects-of-natural-products-on-fructose-induced-nonalcoholic-fatty-liver-disease-nafld
#17
REVIEW
Qian Chen, Tingting Wang, Jian Li, Sijian Wang, Feng Qiu, Haiyang Yu, Yi Zhang, Tao Wang
As a sugar additive, fructose is widely used in processed foods and beverages. Excessive fructose consumption can cause hepatic steatosis and dyslipidemia, leading to the development of metabolic syndrome. Recent research revealed that fructose-induced nonalcoholic fatty liver disease (NAFLD) is related to several pathological processes, including: (1) augmenting lipogenesis; (2) leading to mitochondrial dysfunction; (3) stimulating the activation of inflammatory pathways; and (4) causing insulin resistance...
January 31, 2017: Nutrients
https://www.readbyqxmd.com/read/28138993/arachidonic-acid-containing-phosphatidylcholine-characterized-by-consolidated-plasma-and-liver-lipidomics-as-an-early-onset-marker-for-tamoxifen-induced-hepatic-phospholipidosis
#18
Kosuke Saito, Keisuke Goda, Akio Kobayashi, Naohito Yamada, Kyoko Maekawa, Yoshiro Saito, Shoichiro Sugai
Lipid profiling has emerged as an effective approach to not only screen disease and drug toxicity biomarkers but also understand their underlying mechanisms of action. Tamoxifen, a widely used antiestrogenic agent for adjuvant therapy against estrogen-positive breast cancer, possesses side effects such as hepatic steatosis and phospholipidosis (PLD). In the present study, we administered tamoxifen to Sprague-Dawley rats and used lipidomics to reveal tamoxifen-induced alteration of the hepatic lipid profile and its association with the plasma lipid profile...
January 31, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/28138249/propylthiouracil-induced-liver-failure-and-artificial-liver-support-systems-a-case-report-and-review-of-the-literature
#19
Dong-Bo Wu, En-Qiang Chen, Lang Bai, Hong Tang
BACKGROUND: Antithyroid drugs carry a potential risk of hepatotoxicity. Propylthiouracil (PTU) is commonly prescribed for patients with hyperthyroidism. PTU, however, can induce liver injury, ranging from mild asymptomatic elevation of aminotransferases to acute liver failure (ALF). CASE PRESENTATION: This case reports on a 16-year-old Chinese girl with hyperthyroidism, who was admitted to our hospital for jaundice, nausea, and fatigue associated with severe hyperbilirubinemia and coagulopathy...
2017: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/28128437/schisandrol-b-protects-against-cholestatic-liver-injury-through-pregnane-x-receptor
#20
Hang Zeng, Yiming Jiang, Pan Chen, Xiaomei Fan, Dongshun Li, Aiming Liu, Xiaochao Ma, Wen Xie, Peiqing Liu, Frank J Gonzalez, Min Huang, Huichang Bi
BACKGROUND AND PURPOSE: Currently, ursodeoxycholic acid is the only FDA-approved drug for limited cholestatic liver diseases, and thus the development of new therapeutic approaches is of great importance. This study aimed to evaluate the anti-cholestasis effect of Schisandrol B (SolB), a bioactive compound isolated from Schisandra sphenanthera. EXPERIMENTAL APPROACH: Hepatoprotective effect of SolB against lithocholic acid (LCA)-induced intrahepatic extrahepatic cholestasis was evaluated in mice...
January 27, 2017: British Journal of Pharmacology
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