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Drug induced liver injury

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https://www.readbyqxmd.com/read/28717830/a-review-of-drug-induced-liver-injury-databases
#1
REVIEW
Guangwen Luo, Yiting Shen, Lizhu Yang, Aiping Lu, Zheng Xiang
Drug-induced liver injuries have been a major focus of current research in drug development, and are also one of the major reasons for the failure and withdrawal of drugs in development. Drug-induced liver injuries have been systematically recorded in many public databases, which have become valuable resources in this field. In this study, we provide an overview of these databases, including the liver injury-specific databases LiverTox, LTKB, Open TG-GATEs, LTMap and Hepatox, and the general databases, T3DB, DrugBank, DITOP, DART, CTD and HSDB...
July 17, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28717109/utility-of-human-hepatocyte-spheroids-without-feeder-cells-for-evaluation-of-hepatotoxicity
#2
Takuo Ogihara, Hiroshi Arakawa, Tomoko Jomura, Yoko Idota, Satoshi Koyama, Kentaro Yano, Hajime Kojima
We investigated the utility of three-dimensionally cultured hepatocytes (spheroids) without feeder cells (Sph(f-)) for the prediction of drug-induced liver injury (DILI) in humans. Sph(f-) and spheroids cultured on feeder cells (Sph(f+)) were exposed to the hepatotoxic drugs flutamide, diclofenac, isoniazid and chlorpromazine at various concentrations for 14 days, and albumin secretion and cumulative leakages of toxicity marker enzymes, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and γ-glutamyl transpeptidase (γ-GTP), were measured...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28717101/mechanism-based-risk-assessment-strategy-for-drug-induced-cholestasis-using-the-transcriptional-benchmark-dose-derived-by-toxicogenomics
#3
Taisuke Kawamoto, Yuichi Ito, Osamu Morita, Hiroshi Honda
Cholestasis is one of the major causes of drug-induced liver injury (DILI), which can result in withdrawal of approved drugs from the market. Early identification of cholestatic drugs is difficult due to the complex mechanisms involved. In order to develop a strategy for mechanism-based risk assessment of cholestatic drugs, we analyzed gene expression data obtained from the livers of rats that had been orally administered with 12 known cholestatic compounds repeatedly for 28 days at three dose levels. Qualitative analyses were performed using two statistical approaches (hierarchical clustering and principle component analysis), in addition to pathway analysis...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28713494/caspase-3-role-and-immunohistochemical-expression-in-assessment-of-apoptosis-as-a-feature-of-h1n1-vaccine-caused-drug-induced-liver-injury-dili
#4
Abir Khalil Mohamed, Mona Magdy
BACKGROUND: Drug-Induced Liver Injury (DILI) changes, occur post exposure to natural or chemical compounds including apoptosis. AIM: To assess the H1N1 vaccine-caused DILI by histochemical and immunohistochemical methods. METHODS: This 2014's experimental study was conducted on 70 albino rats. They were given Arepanrix(TM) H1N1 vaccine and were divided into 7 groups; 10 mice each, as control (non-vaccinated), vac2 and vac4 injected with 1(st) and 2(nd) doses of vaccine (suspension only) and euthanized after 3 weeks each, vac5 euthanized 6 weeks after 2(nd) dose, mix2 and mix4 injected with 1(st) and 2(nd) doses of vaccine (mixture of suspension and adjuvant) and euthanized after 3 weeks each, mix5 and euthanized 6 weeks after 2(nd) dose...
May 2017: Electronic Physician
https://www.readbyqxmd.com/read/28712788/antimalarial-agent-artesunate-protects-concanavalin-a-induced-autoimmune-hepatitis-in-mice-by-inhibiting-inflammatory-responses
#5
Xin Zhao, MingJiang Liu, JinGui Li, ShaoJie Yin, YangYang Wu, AnYuan Wang
The anti-malarial drug artesunate (ARS) has been shown to possess anti-inflammatory activity. Its effect on autoimmune hepatitis remains unclear. Concanavalin A (Con A)-induced hepatitis was used in this study to reveal the potential action of ARS and the related mechanism. Mice were pretreated with ARS followed by Con A challenge. Con A caused obvious hepatic injury with higher levels of liver enzymes, elevated pro-inflammatory cytokines and activation of nuclear factor-κB (NF-κB) and mitogen activated protein kinase (MAPK) signaling pathways...
July 13, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28712691/biliary-bile-acids-in-hepatobiliary-injury-what-is-the-link
#6
REVIEW
Peter Fickert, Martin Wagner
The main trigger for liver injury in acquired cholestatic liver disease remains unclear. However, the accumulation of bile acids (BAs) undoubtedly plays a role. Recent progress in deciphering the pathomechanisms of inborn cholestatic liver diseases, decoding mechanisms of BA-induced cell death, and generating modern BA-derived drugs has improved the understanding of the regulation of BA synthesis and transport. Now is the appropriate time to reassess current knowledge about the specific role of BAs in hepatobiliary injury...
July 13, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28702139/ramipril-associated-cholestasis-in-the-setting-of-recurrent-drug-induced-liver-injury
#7
David Forner, Tasha Kulai, Thomas Arnason, Steven E Gruchy, Magnus MacLeod
Aim: Angiotensin-converting enzyme inhibitors (ACEIs) are commonly used to treat hypertension. Although generally well tolerated, the adverse effects of ACEIs include hypotension, cough, acute kidney injury and hyperkalemia. Rare reports of ACEI-induced hepatotoxicity have been described, most notably a cholestatic pattern of injury related to captopril. A 67-year-old male presented to the emergency department with a three-week history of jaundice, pruritis and weakness. Eight weeks before, he began taking ramipril and clopidogrel...
2017: Gastroenterology and Hepatology From Bed to Bench
https://www.readbyqxmd.com/read/28694671/substantial-hepatic-necrosis-is-prognostic-in-fulminant-liver-failure
#8
Paul Ndekwe, Marwan S Ghabril, Yong Zang, Steven A Mann, Oscar W Cummings, Jingmei Lin
AIM: To evaluate if any association existed between the extent of hepatic necrosis in initial liver biopsies and patient survival. METHODS: Thirty-seven patients with fulminant liver failure, whose liver biopsy exhibited substantial necrosis, were identified and included in the study. The histological and clinical data was then analyzed in order to assess the relationship between the extent of necrosis and patient survival, with and without liver transplantation...
June 21, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28691103/role-of-nonalcoholic-fatty-liver-disease-as-risk-factor-for-drug-induced-hepatotoxicity
#9
Julie Massart, Karima Begriche, Caroline Moreau, Bernard Fromenty
BACKGROUND: Obesity is often associated with nonalcoholic fatty liver disease (NAFLD), which refers to a large spectrum of hepatic lesions including fatty liver, nonalcoholic steatohepatitis (NASH) and cirrhosis. Different investigations showed or suggested that obesity and NAFLD are able to increase the risk of hepatotoxicity of different drugs. Some of these drugs could induce more frequently an acute hepatitis in obese individuals whereas others could worsen pre-existing NAFLD. AIM: The main objective of the present review was to collect the available information regarding the role of NAFLD as risk factor for drug-induced hepatotoxicity...
February 2017: Journal of Clinical and Translational Research
https://www.readbyqxmd.com/read/28690936/a-case-of-imatinib-induced-hepatitis
#10
Osman Bhatty, Mohammad Selim, Thamer Kassim, Lakshmi Chintalacheruvu, Manuel Urra, Sonia Shah, Joseph Haggerty, John Gross, Aravdeep Jhand, Gene Pershwitz, Jaya Gupta
A 71-year-old female with a past medical history of Philadelphia chromosome-positive chronic myelogenous leukemia on imatinib therapy, Sjogren's syndrome, and hypothyroidism presents with acute hepatitis. After a comprehensive workup ruling out viral, infectious and metabolic etiologies imatinib is stopped which results in immediate improvement. The biopsy is consistent with drug-induced liver damage; the patient is started on oral prednisone and discharged. Unfortunately, our patient's liver function does not improve over the course of the next week and she is readmitted for hepatic and renal failure...
June 1, 2017: Curēus
https://www.readbyqxmd.com/read/28688954/rifampicin-induced-injury-in-hepg2-cells-is-alleviated-by-tudca-via-increasing-bile-acid-transporters-expression-and-enhancing-the-nrf2-mediated-adaptive-response
#11
Weiping Zhang, Lihong Chen, Hui Feng, Wei Wang, Yi Cai, Fen Qi, Xiaofang Tao, Jun Liu, Yujun Shen, Xiaofei Ren, Xi Chen, Jianming Xu, Yuxian Shen
Bile acid transporters and the nuclear factor erythroid 2-related factor (Nrf-2)-mediated adaptive response play important roles in the development of drug-induced liver injury (DILI). However, little is known about the contribution of the adaptive response to rifampicin (RFP)-induced cell injury. In this study, we found RFP decreased the survival rate of HepG2 cells and increased the levels of lactate dehydrogenase (LDH), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AKP), γ-glutamyl-transferase (γ-GT), total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin (IBIL), total bile acid (TBA) and adenosine triphosphate (ATP) in the cell culture supernatants in both a concentration- and a time-dependent manner...
July 5, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28688898/liver-biopsy-findings-in-patients-with-hematopoietic-cell-transplantation
#12
Farzan Eskandari, Daniel Rowan, Parameswaran Hari, Jonathan Kapke, Robert Schneidewend, Catherine Hagen, Kiyoko Oshima
Liver dysfunction is a frequent complication after hematopoietic-cell transplantation (HCT). Liver biopsy has an important role for confirming the diagnosis of graft versus host disease (GVHD) or other liver diseases. The histological features of GVHD are not specific, and GVHD and other coexisting diseases may be present in the same biopsy, which makes the histologic interpretation of the liver biopsy more complex and challenging. The aim of the study is to improve the present diagnostic criteria. 52 liver biopsies were studied...
July 5, 2017: Human Pathology
https://www.readbyqxmd.com/read/28687704/synergistic-cytotoxicity-from-drugs-and-cytokines-in-vitro-as-an-approach-to-classify-drugs-according-to-their-potential-to-cause-idiosyncratic-hepatotoxicity-a-proof-of-concept-study
#13
Ashley R Maiuri, Bronlyn Wassink, Jonathan D Turkus, Anna B Breier, Theresa Lansdell, Gurpreet Kaur, Sarah L Hession, Patricia E Ganey, Robert A Roth
Idiosyncratic, drug-induced liver injury (IDILI) typically occurs in a small fraction of patients and has resulted in removal of otherwise efficacious drugs from the market. Current preclinical testing methods are ineffective in predicting which drug candidates have IDILI liability. Recent results suggest that immune mediators such as tumor necrosis factor-alpha (TNF) and interferon-gamma (IFN) interact with drugs that cause IDILI to kill hepatocytes. This proof-of-concept study was designed to test the hypothesis that drugs can be classified according to their ability to cause IDILI in humans using logistic regression modeling with covariates derived from concentration-response relationships that describe cytotoxic interaction with cytokines...
July 7, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28684216/evaluation-of-dna-damage-in-wistar-rat-tissues-with-hyperlipidemia-induced-by-tyloxapol
#14
Joubert Aires de Sousa, Patrícia Pereira, Mariangela da Costa Allgayer, Norma Possa Marroni, Alexandre de Barros Falcão Ferraz, Jaqueline Nascimento Picada
Hyperlipidemia is characterized by high levels of plasma triglycerides and LDL-cholesterol, accompanied by reduced HDL-cholesterol levels, and is often associated with an increased risk of cardiovascular diseases. However, few studies have shown the effects of hyperlipidemia on genomic stability. The aim of this study was to evaluate DNA damage provided by tyloxapol induced hyperlipidemia. Tyloxapol, a non-ionic surfactant, which increases the activity of the enzyme HMG-CoA reductase and decreases clearance of lipoproteins, was used to induce hyperlipidemia in Wistar rats...
July 3, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/28678845/polymerase-free-measurement-of-microrna-122-with-single-base-specificity-using-single-molecule-arrays-detection-of-drug-induced-liver-injury
#15
David M Rissin, Barbara López-Longarela, Salvatore Pernagallo, Hugh Ilyine, A D Bastiaan Vliegenthart, James W Dear, Juan J Díaz-Mochón, David C Duffy
We have developed a single probe method for detecting microRNA from human serum using single molecule arrays, with sequence specificity down to a single base, and without the use of amplification by polymerases. An abasic peptide nucleic acid (PNA) probe-containing a reactive amine instead of a nucleotide at a specific position in the sequence-for detecting a microRNA was conjugated to superparamagnetic beads. These beads were incubated with a sample containing microRNA, a biotinylated reactive nucleobase-containing an aldehyde group-that was complementary to the missing base in the probe sequence, and a reducing agent...
2017: PloS One
https://www.readbyqxmd.com/read/28677736/glutathione-peroxidase-3-is-a-protective-factor-against-acetaminophen%C3%A2-induced-hepatotoxicity-in-vivo-and-in-vitro
#16
Syu-Ichi Kanno, Ayako Tomizawa, Shin Yomogida, Akiyoshi Hara
Acetaminophen (APAP) is a widely available antipyretic and analgesic; however, overdose of the drug inflicts severe damage to the liver. It is well established that the hepatotoxicity of APAP is initiated by formation of a reactive metabolite, N‑acetyl‑p‑benzoquinone imine (NAPQI), which can be detoxified by conjugation with reduced glutathione (GSH), a typical antioxidant. We recently found that the blood mRNA expression level of glutathione peroxidase 3 (Gpx3), which catalyzes the oxidation of GSH, is associated with the extent of APAP‑induced hepatotoxicity in mice...
July 3, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28675791/olprinone-protects-liver-from-ischemia-reperfusion-injury-through-oxidative-stress-prevention-and-protein-kinase-akt-activation
#17
Mohamed Bejaoui, Mohamed Amine Zaouali, Rim Sakly, Hassen Ben Abdennebi
Liver ischemia reperfusion (IR) injury is inevitable in surgical procedures such as hepatic resection and liver transplantation. It represents a leading cause of liver graft dysfunction and primary non function after transplantation. Phosphodiesterase (PDE) inhibitors are emerging as effective drugs able to reduce IR damage. The aim of this study was to investigate the effect of selective PDE-3 inhibitor olprinone (Olp) against liver IR injury. Male Wistar rats were subjected to one hour of partial warm ischemia (70%) followed by six hours of reperfusion...
July 4, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28675685/challenges-and-difficulties-in-pathological-diagnosis-of-autoimmune-hepatitis
#18
REVIEW
Kenichi Harada, Nguyen Canh Hiep, Hiromasa Ohira
Autoimmune hepatitis (AIH) with acute presentation is widely recognized as a distinct clinical entity, and its clinicopathology has been extensively studied. In most cases, AIH with acute presentation is merely acute exacerbation of classical chronic AIH, but pure acute-onset AIH without previous symptoms of chronic liver disease is also encountered. Rapid diagnosis and initiation of immunosuppressive treatment are necessary for both acute exacerbation and acute-onset to prevent fatal liver failure. The diagnostic criteria commonly used for classical AIH are generally applicable to acute exacerbation, but acute-onset AIH may present with additional pathological features...
July 3, 2017: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/28675031/efficient-two-photon-fluorescent-probe-for-glutathione-s-transferase-detection-and-imaging-in-drug-induced-liver-injury-sample
#19
Jing Zhang, Zhen Jin, Xiao-Xiao Hu, Hong-Min Meng, Jin Li, Xiao-Bing Zhang, Hong-Wen Liu, Tanggang Deng, Shan Yao, Lili Feng
Drug-induced liver injury (DILI) is a potential complication of any prescribed medication. So far, the diagnosis of DILI is still a clinical challenge due to the lack of efficient diagnosis method. Glutathione S-transferase (GST), with a high concentration in liver cytosol, can reduce toxicity and facilitate urinary excretion by catalyzing the conjugation of glutathione (GSH) with reactive metabolites in liver. When liver is seriously damaged, GST and GSH will be released into plasma from liver cytosol, which caused a lower GST activity in liver cytosol...
July 4, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28674842/clinical-relevance-and-predictive-value-of-damage-biomarkers-of-drug-induced-kidney-injury
#20
Sandra L Kane-Gill, Pamela L Smithburger, Kianoush Kashani, John A Kellum, Erin Frazee
Nephrotoxin exposure accounts for up to one-fourth of acute kidney injury episodes in hospitalized patients, and the associated consequences are as severe as acute kidney injury due to other etiologies. As the use of nephrotoxic agents represents one of the few modifiable risk factors for acute kidney injury, clinicians must be able to identify patients at high risk for drug-induced kidney injury rapidly. Recently, significant advancements have been made in the field of biomarker utilization for the prediction and detection of acute kidney injury...
July 3, 2017: Drug Safety: An International Journal of Medical Toxicology and Drug Experience
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