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drug-induced liver injury

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https://www.readbyqxmd.com/read/29792895/pharmacogenomics-of-drug-induced-liver-injury-dili-molecular-biology-to-clinical-applications
#1
REVIEW
Kalaiyarasi Kaliyaperumal, Jane I Grove, Robin M Delahay, William J H Griffiths, Adam Duckworth, Guruprasad P Aithal
A number of drug-specific and host-related factors contribute to the development of drug-induced liver injury (DILI). Investigations focused on genetic susceptibility to DILI have advanced our understanding of the pathogenesis of this rare, yet potentially life-threatening adverse reaction. Candidate gene studies involving well-characterized patients with DILI and drug-exposed controls have identified single nucleotide polymorphisms (SNPs) affecting the metabolism and clearance of specific drugs and hence, influencing individual's susceptibility to DILI...
May 21, 2018: Journal of Hepatology
https://www.readbyqxmd.com/read/29791258/licorice-root-extract-and-magnesium-isoglycyrrhizinate-protect-against-triptolide-induced-hepatotoxicity-via-up-regulation-of-the-nrf2-pathway
#2
Qin-You Tan, Qian Hu, Sheng-Nan Zhu, Lu-Lu Jia, Juan Xiao, Hua-Zhen Su, Shao-Yuan Huang, Jing Zhang, Junfei Jin
Triptolide, the predominant biologically active component of the Chinese herb Tripterygium wilfordii Hook f., possesses numerous pharmacological activities, including anti-inflammatory, anti-fertility, anti-neoplastic, and immunosuppressive effects. However, toxicity and severe adverse effects, particularly hepatotoxicity, limit the clinical application of triptolide. Licorice root extract contains various bioactive compounds and is potent hepatoprotective. Magnesium isoglycyrrhizinate, a magnesium salt of the 18α-glycyrrhizic acid stereoisomer of glycyrrhizic acid, is used clinically in China to treat chronic viral hepatitis and acute drug-induced liver injury...
November 2018: Drug Delivery
https://www.readbyqxmd.com/read/29791174/-drug-and-herbal-hepatotoxicity-an-overview-of-clinical-classifications
#3
Mária Szántová, Jozef Sedlačko, Martina Jakabovičová
Drug induced liver injury (DILI) is often underdiagnosed disease with increasing incidence. In developed countries it belongs to the leading causes of acute liver failure. Risk groups are women and persons older than 60 years. The work summarizes the up to date information on diagnosis and mostly used classifications on DILI. It is quite often and serious complication of medicament therapy. DILI belongs to the most often cause of acute hepatic failure in the old age in developed countries. Diagnostic procedure includes medical history (time correlation with drug intake), clinical symptoms and blood tests...
2018: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/29788883/models-of-drug-induced-liver-injury-dili-current-issues-and-future-perspectives
#4
Lucija Kuna, Ivana Bozic, Tomislav Kizivat, Kristina Bojanic, Margareta Mrso, Edgar Kralj, Robert Smolic, George Y Wu, Martina Smolic
Drug-induced liver injury (DILI) is an important cause of acute liver failure cases in the United States, and remains a common cause of withdrawal of drugs in both preclinical and clinical phases. In this article, we review the existing knowledge of appropriate models to study DILI in vitro and in vivo with special focus on hepatic cell models, variations of 3D co-cultures, animal models, databases and predictive modeling and translational biomarkers developed to understand the mechanisms and pathophysiology of DILI...
May 22, 2018: Current Drug Metabolism
https://www.readbyqxmd.com/read/29788510/predicting-drug-induced-liver-injury-using-ensemble-learning-methods-and-molecular-fingerprints
#5
Haixin Ai, Wen Chen, Li Zhang, Liangchao Huang, Zimo Yin, Huan Hu, Qi Zhao, Jian Zhao, Hongsheng Liu
Drug-induced liver injury (DILI) is a major safety concern in the drug-development process, and various methods have been proposed to predict the hepatotoxicity of compounds during the early stages of drug trials. In this study, we developed an ensemble model using three machine learning algorithms and 12 molecular fingerprints from a dataset containing 1,241 diverse compounds. The ensemble model achieved an average accuracy of 71.1±2.6%, sensitivity of 79.9±3.6%, specificity of 60.3±4.8%, and area under the receiver operating characteristic curve (AUC) of 0...
May 21, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29786560/microfabrication-of-liver-and-heart-tissues-for-drug-development
#6
REVIEW
Grace E Brown, Salman R Khetani
Drug-induced liver- and cardiotoxicity remain among the leading causes of preclinical and clinical drug attrition, marketplace drug withdrawals and black-box warnings on marketed drugs. Unfortunately, animal testing has proven to be insufficient for accurately predicting drug-induced liver- and cardiotoxicity across many drug classes, likely due to significant differences in tissue functions across species. Thus, the field of in vitro human tissue engineering has gained increasing importance over the last 10 years...
July 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29785833/species-differences-in-bile-acids-i-plasma-and-urine-bile-acid-composition
#7
Rhishikesh Thakare, Jawaher Abdullah Alamoudi, Nagsen Gautam, A David Rodrigues, Yazen Alnouti
Maintenance of bile acid (BA) homeostasis is essential to achieve their physiologic functions and avoid their toxic effects. The marked differences in BA composition between preclinical safety models and humans may play a major role in the poor prediction of drug-induced liver injury using preclinical models. We compared the composition of plasma and urinary BAs and their metabolites between humans and several animal species. Total BA pools and their composition varied widely among different species. Highest sulfation of BAs was observed in human and chimpanzee...
May 21, 2018: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/29785262/evaluation-of-the-relevance-of-dili-predictive-hypotheses-in-early-drug-development-review-of-in-vitro-methodologies-vs-bddcs-classification
#8
Rosa Chan, Leslie Z Benet
Drug-induced liver injury (DILI) is a major safety concern; it occurs frequently; it is idiosyncratic; it cannot be adequately predicted; and a multitude of underlying mechanisms has been postulated. A number of experimental approaches to predict human DILI have been proposed utilizing in vitro screening such as inhibition of mitochondrial function, hepatobiliary transporter inhibition, reactive metabolite formation with and without covalent binding, and cellular health, but they have achieved only minimal success...
May 8, 2018: Toxicology Research
https://www.readbyqxmd.com/read/29785189/the-investigation-of-the-effect-and-mechanism-of-sophora-moorcroftiana-alkaloids-in-combination-with-albendazole-on-echinococcosis-in-an-experimental-rats-model
#9
Fabin Zhang, Chunhui Hu, Shilei Cheng, Shulin Wang, Bin Li, Deping Cao, Haining Fan, Ruchong Pan, Mei Yang, Yanhui Xu
Echinococcosis is a worldwide anthropozoonosis which is highly endemic over large animal husbandry areas in northwestern China. The current clinical therapeutic medicine against echinococcosis is albendazole, although it caused serious side effects in patients. The component in traditional Chinese herb medicine, Sophora moorcroftiana alkaloids (SA), is thought to be a potential drug to treat echinococcosis. In order to explore the effect and mechanism of SA treatment against echinococcosis, we established animal echinococcosis model and treated rats with albendazole alone, alkaloids alone, and combined therapy...
2018: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/29784840/oxidative-stress-and-first-line-antituberculosis-drug-induced-hepatotoxicity
#10
Wing Wai Yew, Kwok Chiu Chang, Denise P Chan
Hepatotoxicity induced by antituberculosis drugs is a serious adverse reaction with significant morbidity and even rarely mortality. This form of toxicity potentially impacts the treatment outcome of tuberculosis in some patients. Confining to first-line antituberculosis drugs, this review addresses whether and how oxidative stress, and more broadly, disturbance in redox homeostasis alongside mitochondrial dysfunction, may contribute to the hepatotoxicity induced by them. Risk factors for such toxicity that have been identified, in addition to genetic factors, principally include old age, malnutrition, alcoholism, chronic hepatitis C and chronic hepatitis B infection, HIV infection and pre-existing liver disease...
May 21, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29781872/nat2-ultra-slow-acetylator-and-risk-of-anti-tuberculosis-drug-induced-liver-injury-a-genotype-based-meta-analysis
#11
Supharat Suvichapanich, Koya Fukunaga, Hilyatuz Zahroh, Taisei Mushiroda, Surakameth Mahasirimongkol, Licht Toyo-Oka, Usa Chaikledkaew, Jiraphun Jittikoon, Rika Yuliwulandari, Hideki Yanai, Sukanya Wattanapokayakit, Katsushi Tokunaga
BACKGROUND: NAT2 slow acetylator is a confirmed risk of anti-tuberculosis drug-induced liver injury (ATDILI). However, NAT2 ultra-slow acetylators, a new refinement among NAT2 slow acetylators, have been recently proposed. The patients with NAT2 genotypes of *6A/*6A, *6A/*7B and *7B/*7B are referred to in this group. OBJECTIVE: We aim to prove an association of the NAT2 ultra-slow acetylators with the risk of ATDILI. MATERIALS AND METHODS: Systematic review and meta-analysis were performed based on each NAT2 genotype and risk of ATDILI cases and also new classification of the ultra-slow acetylators up to 31 October 2016...
May 17, 2018: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/29781282/evaluating-drug-induced-liver-injury-and-its-remission-via-discrimination-and-imaging-of-hclo-and-h2s-with-a-two-photon-fluorescent-probe
#12
Xiaoyun Jiao, Yongsheng Xiao, Yong Li, Muwen Liang, Xilei Xie, Xu Wang, Bo Tang
Drug-induced liver injury (DILI) has aroused wide concern. Finding new markers or indicators as well as detoxification molecules for DILI are of great significance and good application prospect, which can help develop effective preclinical screening methodology and corresponding treatment protocols. Herein, in this paper, DILI caused by antidepressant drugs of duloxetine and fluoxetine and its remission were evaluated by a two-photon fluorescent probe, RPC-1, through discriminating and imaging HClO and H2S simultaneously...
May 21, 2018: Analytical Chemistry
https://www.readbyqxmd.com/read/29778019/phoenix-dactylifera-protects-against-oxidative-stress-and-hepatic-injury-induced-by-paracetamol-intoxication-in-rats
#13
Gamal A Salem, Ahmed Shaban, Hussain A Diab, Wesam A Elsaghayer, Manal D Mjedib, Aomassad M Hnesh, Ravi P Sahu
The current studies were sought to determine effects of antioxidant potential of aqueous and methanolic extracts of Phoenix dactylifera leaves (PLAE and PLME) against the widely-used analgesic paracetamol (PCM) induced hepatotoxicity. Groups of rats were treated with or without PCM (1500 mg/kg), PLAE and PLME (300 mg/kg) and n-acetylcysteine (NAC, 50 mg/kg) followed by assessments of liver function tests, oxidative stress, antioxidant defenses, and hepatotoxicity. We observed that PCM significantly elevated serum liver markers, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), and bilirubin compared to control (untreated) group...
May 16, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29774767/the-role-of-hepatic-antioxidant-capacity-and-hepatobiliary-transporter-in-liver-injury-induced-by-isopsoralen-in-zebrafish-larvae
#14
Y Zhang, Y Zhang, J Li, Y Chen, L Han, Q He, J Chu, K Liu
Isopsoralen is the main component of the Chinese medicine psoralen, which has antitumour activity and can be used for the treatment of osteoporosis. However, the mechanism behind its hepatotoxicity has not yet been elucidated. In this study, the hepatotoxicity of isopsoralen was investigated using zebrafish. Isopsoralen treatment groups of 25, 50 and 100 μM were established. The mortality, liver morphology changes, levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), liver histopathology and mRNA levels of liver injury-related genes in zebrafish larvae were measured...
January 1, 2018: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/29774570/high-mobility-group-box-1-drives-fibrosis-progression-signaling-via-the-receptor-for-advanced-glycation-end-products-in-mice
#15
Xiaodong Ge, Elena Arriazu, Fernando Magdaleno, Daniel J Antoine, Rouchelle Dela Cruz, Neil Theise, Natalia Nieto
BACKGROUND & RATIONALE: High-mobility group box-1 (HMGB1) is a damage-associated molecular pattern (DAMP) increased in response to liver injury. Since HMGB1 is a ligand for the receptor for advanced glycation end-products (RAGE), we hypothesized that induction of HMGB1 could participate in the pathogenesis of liver fibrosis via RAGE cell-specific signaling mechanisms. RESULTS: liver HMGB1 protein expression correlated with fibrosis stage in patients with chronic Hepatitis C virus (HCV) infection, primary biliary cirrhosis (PBC) and alcoholic steatohepatitis (ASH)...
May 18, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29771932/a-multi-center-preclinical-study-of-gadoxetate-dce-mri-in-rats-as-a-biomarker-of-drug-induced-inhibition-of-liver-transporter-function
#16
Anastassia Karageorgis, Stephen C Lenhard, Brittany Yerby, Mikael F Forsgren, Serguei Liachenko, Edvin Johansson, Mark A Pilling, Richard A Peterson, Xi Yang, Dominic P Williams, Sharon E Ungersma, Ryan E Morgan, Kim L R Brouwer, Beat M Jucker, Paul D Hockings
Drug-induced liver injury (DILI) is a leading cause of acute liver failure and transplantation. DILI can be the result of impaired hepatobiliary transporters, with altered bile formation, flow, and subsequent cholestasis. We used gadoxetate dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), combined with pharmacokinetic modelling, to measure hepatobiliary transporter function in vivo in rats. The sensitivity and robustness of the method was tested by evaluating the effect of a clinical dose of the antibiotic rifampicin in four different preclinical imaging centers...
2018: PloS One
https://www.readbyqxmd.com/read/29770511/liver-enzyme-abnormalities-of-inpatients-with-rheumatic-diseases-a-10-year-retrospective-study-in-a-korean-medicine-hospital
#17
Hyeonhoon Lee, Seunghoon Lee, Jung Won Kang, Jae-Dong Lee
Herbal medicines have been used as a treatment option for rheumatic disease (RD), but they often produce liver enzyme abnormality. This study examines the incidence of herb-induced liver injury (HILI) and the relationship between risk factors and liver enzyme abnormality (LEA) in inpatients with RD. HILI was analyzed using the Roussel Uclaf causality assessment method liver injury criteria and causality assessment. Multivariable analysis was performed to assess the relationship between patient characteristics and LEA in RD...
May 16, 2018: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/29764210/curative-ex-vivo-hepatocyte-directed-gene-editing-in-a-mouse-model-of-hereditary-tyrosinemia-type-1
#18
Caitlin VanLith, Rebekah Guthman, Clara T Nicolas, Kari Allen, Zeji Du, Dong Jin Joo, Scott L Nyberg, Joseph B Lillegard, Raymond Daniel Hickey
Hereditary tyrosinemia type 1 (HT1) is an autosomal recessive disorder caused by deficiency of fumarylacetoacetate hydrolase (FAH). It has been previously shown that ex vivo hepatocyte-directed gene therapy using an integrating lentiviral vector to replace the defective Fah gene can cure liver disease in small and large animal models of HT1. In this study, we hypothesized that ex vivo hepatocyte-directed gene editing using CRISPR-Cas9 could be used to correct a mouse model of HT1, in which a single point mutation results in loss of FAH function...
May 15, 2018: Human Gene Therapy
https://www.readbyqxmd.com/read/29761207/omics-based-responses-induced-by-bosentan-in-human-hepatoma-heparg-cell-cultures
#19
Robim M Rodrigues, Laxmikanth Kollipara, Umesh Chaudhari, Agapios Sachinidis, René P Zahedi, Albert Sickmann, Annette Kopp-Schneider, Xiaoqi Jiang, Hector Keun, Jan Hengstler, Marlies Oorts, Pieter Annaert, Eef Hoeben, Eva Gijbels, Joery De Kock, Tamara Vanhaecke, Vera Rogiers, Mathieu Vinken
Bosentan is well known to induce cholestatic liver toxicity in humans. The present study was set up to characterize the hepatotoxic effects of this drug at the transcriptomic, proteomic, and metabolomic levels. For this purpose, human hepatoma-derived HepaRG cells were exposed to a number of concentrations of bosentan during different periods of time. Bosentan was found to functionally and transcriptionally suppress the bile salt export pump as well as to alter bile acid levels. Pathway analysis of both transcriptomics and proteomics data identified cholestasis as a major toxicological event...
May 14, 2018: Archives of Toxicology
https://www.readbyqxmd.com/read/29753871/combinatorial-usage-of-fungal-polysaccharides-from-cordyceps-sinensis-and-ganoderma-atrum-ameliorate-drug-induced-liver-injury-in-mice
#20
Songtao Fan, Xiaojun Huang, Sunan Wang, Chang Li, Zhihong Zhang, Mingyong Xie, Shaoping Nie
This study investigated the possible protective effect of combined fungal polysaccharides (CFP), consisting of Cordyceps sinensis polysaccharides (CSP) and Ganoderma atrum polysaccharides (PSG) with well-defined structural characteristics, against cyclophosphamide (CTX)-induced hepatotoxicity in mice. Our results indicated CFP effectively prevented the liver injury by decreasing toxicity markers (aspartate transaminase, alanine aminotransferase and alkaline phosphatase). Further biochemical and molecular analysis indicated CSP particularly inhibited the activation of Toll-like receptor 9 (TLR9) and its related inflammatory signals, including pro-inflammatory cytokines, inducible nitric oxide synthase, and cyclooxygenase-2 to modulate hepatic inflammation response...
May 10, 2018: Food and Chemical Toxicology
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