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Drug induced liver injury

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https://www.readbyqxmd.com/read/29352069/identification-of-ketene-reactive-intermediate-of-erlotinib-possibly-responsible-for-inactivation-of-p450-enzymes
#1
Huimin Zhao, Siyuan Li, Zixin Yang, Ying Peng, Xiaohui Chen, Jiang Zheng
Erlotinib (ELT), a tyrosine kinase inhibitor, is widely used for the treatment of non-small-cell lung cancer in clinic. Unfortunately, severe drug-induced liver injury and other adverse effects occurred during the treatment. Meanwhile, ELT has been reported to be a mechanism-based inactivator of CYPs 3A4 and 3A5. The objectives of this study were to identify ketene intermediate of ELT and investigate the association of the acetylenic bioactivation with the enzyme inactivation caused by ELT. A ketene intermediate was detected in human microsomal incubations of ELT, using 4-bromobenzylamine as a trapping agent...
January 19, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29343011/-molecular-genetic-mechanism-of-anti-tuberculous-drug-induced-liver-injury
#2
Q Sun, H P Xiao
No abstract text is available yet for this article.
January 12, 2018: Chinese Journal of Tuberculosis and Respiratory Diseases
https://www.readbyqxmd.com/read/29338970/baicalein-and-baicalin-alleviate-acetaminophen-induced-liver-injury-by-activating-nrf2-antioxidative-pathway-the-involvement-of-erk1-2-and-pkc
#3
Liang Shi, Zhanxia Hao, Shaobo Zhang, Mengjuan Wei, Bin Lu, Zhengtao Wang, Lili Ji
Acetaminophen (APAP)-induced hepatotoxicity is the main cause of drug-induced liver injury. This study investigated the protection of baicalin and its aglycone baicalein against APAP-induced hepatotoxicity and its mechanism. Baicalein and baicalin alleviated APAP-induced hepatotoxicity both in vitro and in vivo. Moreover, baicalin-provided this protection was not diminished in hepatocytes or mice treated with β-glucuronidase inhibitor. Results of liver glutathione (GSH) and reactive oxygen species (ROS) formation demonstrated the alleviation of baicalein and baicalin on APAP-induced liver oxidative stress injury...
January 12, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29337684/hepatotoxicity-associated-with-statins
#4
Bensu Karahalil, Emine Hare, Göksel Koç, İrem Uslu, Kerem Şentürk, Yağmur Özkan
Treatment with statins is known all over the world. They are generally considered safe at therapeutic doses. Nevertheless, clinical trials are not enough to assess their scarce adverse effects such as idiosyncratic drug induced liver injury (DILI). Due to some conditions, such as concomitant usage (drug-drug interaction using an identical metabolising enzyme) and genetic polymorphisms, there is an increasing concern about their safety. Hepatotoxicity and rhabdomyolysis have begun to appear in published studies...
December 20, 2017: Arhiv za Higijenu Rada i Toksikologiju
https://www.readbyqxmd.com/read/29331651/activation-of-p62-keap1-nrf2-antioxidant-pathway-in-the-early-stage-of-acetaminophen-induced-acute-liver-injury-in-mice
#5
Zhenyu Shen, Yu Wang, Zhenhui Su, Ruirui Kou, Keqin Xie, Fuyong Song
Acetaminophen (APAP) overdose can cause severe liver failure even death. Nearly half of drug-induced liver injury is attributed to APAP in the US and many European countries. Oxidative stress has been validated as a critical event involved in APAP-induced liver failure. p62/SQSTM1, a selective autophagy adaptor protein, is reported to regulate Nrf2-ARE antioxidant pathway in response to oxidative stress. However, the exact role of p62-keap1-Nrf2 antioxidant pathway in APAP-induced hepatotoxicity remains unknown...
January 10, 2018: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29329425/comparison-of-hepatic-2d-sandwich-cultures-and-3d-spheroids-for-long-term-toxicity-applications-a-multi-center-study
#6
Catherine C Bell, Anita C A Dankers, Volker M Lauschke, Rowena Sison-Young, Roz Jenkins, Cliff Rowe, Chris Goldring, Kevin Park, Sophie Regan, Tracy Walker, Chris Schofield, Audrey Baze, Alison J Foster, Dominic Williams, Amy W M van de Ven, Frank Jacobs, Jos van Houdt, Tuula Lähteenmäki, Jan Snoeys, Satu Juhila, Lysiane Richert, Magnus Ingelman-Sundberg
Primary human hepatocytes (PHH) are commonly used for in vitro studies of drug-induced liver injury. However, when cultured as 2D monolayers, PHH lose crucial hepatic functions within hours. This dedifferentiation can be ameliorated when PHH are cultured in sandwich configuration (2Dsw), particularly when cultures are regularly re-overlaid with extracellular matrix, or as 3D spheroids. In this study, the six participating laboratories evaluated the robustness of these two model systems made from cryopreserved PHH from the same donors considering both inter-donor and inter-lab variability and compared their suitability for use in repeated-dose toxicity studies using 5 different hepatotoxins with different toxicity mechanisms...
January 10, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29324638/molecular-research-on-drug-induced-liver-injury
#7
EDITORIAL
Rolf Teschke, Gaby Danan
Drugs may cause liver injury in a few susceptible individuals, but the molecular events that lead to this idiosyncratic, largely dose-independent and non-predictable drug-induced liver injury (DILI) are mostly unknown, since animal models to explore the pathogenetic mechanisms of human idiosyncratic DILI are not yet reliable.[...].
January 11, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29323538/clinical-characteristics-and-outcomes-of-traditional-chinese-medicine-induced-liver-injury-a-systematic-review
#8
Ran Wang, Xingshun Qi, Eric Yoshida, Nahum Mendez-Sanchez, Rolf Teschke, Mingyu Sun, Xu Liu, Chunping Su, Jiao Deng, Han Deng, Feifei Hou, Xiaozhong Guo
BACKGROUNDS: Traditional Chinese medicine (TCM) is becoming increasingly popular and related adverse events are often ignored or underestimated. AIMS: This systematic review aimed to evaluate the clinical characteristics and outcomes of TCM-induced liver injury (TCM-ILI) and to estimate the proportion of TCM-ILI in all drug-induced liver injuries (DILI). METHODS: China National Knowledge Infrastructure, Wanfang, VIP, PubMed, and Embase databases were searched...
January 11, 2018: Expert Review of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/29319822/an-animal-model-of-abacavir-induced-hla-mediated-liver-injury
#9
Binbin Song, Shigeki Aoki, Cong Liu, Takeshi Susukida, Kousei Ito
Genome-wide association studies indicate that several idiosyncratic adverse drug reactions are highly associated with specific human leukocyte antigen (HLA) alleles. For instance, abacavir, a human immunodeficiency virus reverse transcriptase inhibitor, induces multi-organ toxicity exclusively in patients carrying the HLA-B*57:01 allele. However, the underlying mechanism is unclear due to a lack of appropriate animal models. Previously, we developed HLA-B*57:01 transgenic mice and found that topical application of abacavir to the ears induced proliferation of CD8+ lymphocytes in local lymph nodes...
January 8, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29316113/drug-induced-liver-injury-is-frequently-associated-with-severe-cutaneous-adverse-drug-reactions-experience-from-two-australian-tertiary-hospitals
#10
Wendy C Fang, Nikki R Adler, Linda V Graudins, Caitlin Goldblatt, Michelle Sy Goh, Stuart K Roberts, Jason A Trubiano, Ar Kar Aung
BACKGROUND: Drug-induced liver injury can be associated with certain cutaneous adverse drug reactions. AIMS: We aim to demonstrate the prevalence of drug-induced liver injury in patients with cutaneous adverse drug reactions. Severity and patterns of liver injury, risk factors, causal medications and outcomes are also examined. METHODS: A retrospective cohort study of patients with cutaneous adverse drug reactions was conducted across two hospitals in Australia...
January 8, 2018: Internal Medicine Journal
https://www.readbyqxmd.com/read/29312593/shikonin-induces-ros-based-mitochondria-mediated-apoptosis-in-colon-cancer
#11
Wenquan Liang, Jianxin Cui, Kecheng Zhang, Hongqing Xi, Aizhen Cai, Jiyang Li, Yunhe Gao, Chong Hu, Yi Liu, Yixun Lu, Ning Wang, Xiaosong Wu, Bo Wei, Lin Chen
Colon cancer is the third most common malignancy worldwide, and chemotherapy is a widely used strategy in clinical therapy. Chemotherapy-resistant of colon cancer is the main cause of recurrence and progression. Novel drugs with efficacy and safety in treating colon cancer are urgently needed. Shikonin, a naphthoquinone derived from the roots of the herbal plant Lithospermum erythrorhizon, has been determined to be a potent anti-tumor agent. The aim of the present study was to detect the underlying anti-tumor mechanism of shikonin in colon cancer...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29310474/low-prevalence-of-hepatitis-e-in-iceland-a-seroepidemiological-study
#12
Arthur Löve, Thora B Björnsdottir, Sigurdur Olafsson, Einar S Björnsson
OBJECTIVE: Hepatitis E virus (HEV) infection has been reported to be more prevalent in the developed countries than previously thought. HEV infection is an important differential diagnosis in patients with drug-induced liver injury (DILI). The prevalence of hepatitis E was investigated in the general population of Iceland, among pig farmers and patients with DILI. MATERIALS AND METHODS: Serum samples were tested for hepatitis E IgG, with two commercial ELISA tests: Diagnostic Bioprobes Srl...
January 8, 2018: Scandinavian Journal of Gastroenterology
https://www.readbyqxmd.com/read/29309877/development-of-a-mechanistic-biokinetic-model-for-hepatic-bile-acid-handling-to-predict-possible-cholestatic-effects-of-drugs
#13
Sylvia Notenboom, Karl M Weigand, Johannes H Proost, Marola M van Lipzig, Evita van de Steeg, Petra H H van den Broek, Rick Greupink, Frans G M Russel, Geny M M Groothuis
Drug-induced liver injury (DILI) is a common reason for drug withdrawal from the market. An important cause of DILI is drug-induced cholestasis. One of the major players involved in drug-induced cholestasis is the bile salt efflux pump (BSEP; ABCB11). Inhibition of BSEP by drugs potentially leads to cholestasis due to increased (toxic) intrahepatic concentrations of bile acids with subsequent cell injury. In order to investigate the possibilities for in silico prediction of cholestatic effects of drugs, we developed a mechanistic biokinetic model for human liver bile acid handling populated with human in vitro data...
January 5, 2018: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29308212/-the-efficacy-of-extracorporeal-liver-support-with-molecular-adsorbent-recirculating-system-in-severe-drug-induced-liver-injury
#14
Jaishvi Eapen, Rotimi Ayoola, Ram M Subramanian
We report a case of a 26-year-old man with no significant medical history, who presented with fatigue, pruritus, jaundice, dark urine and clay colored stool for one month. He had been taking methyl-1-etiochoenolol-epietiocholanolone, an androgenic anabolic steroid (AAS). He was initially found to have a total bilirubin (Tbili) of 6 mg/dL. He discontinued the AAS but the patients' symptoms worsened and Tbili increased to 36 mg/d. This prompted inpatient management of his drug-induced liver injury (DILI). Molecular adsorbent recirculating system (MARS) is an extracorporeal liver support system that replaces the detoxification function of the liver...
January 2018: Oxford Medical Case Reports
https://www.readbyqxmd.com/read/29307848/herbal-and-dietary-supplement-induced-liver-injuries-in-the-spanish-dili-registry
#15
Inmaculada Medina-Caliz, Miren Garcia-Cortes, Andres Gonzalez-Jimenez, Maria R Cabello, Mercedes Robles-Diaz, Judith Sanabria-Cabrera, Rocio Sanjuan-Jimenez, Aida Ortega-Alonso, Beatriz García-Muñoz, Inmaculada Moreno, Miguel Jimenez-Perez, M Carmen Fernandez, Pere Ginés, Martin Prieto, Isabel Conde, Hacibe Hallal, German Soriano, Eva Roman, Agustin Castiella, Encarnacion Blanco-Reina, Maria R Montes, Marta Quiros-Cano, Flores Martin-Reyes, M Isabel Lucena, Raul J Andrade
BACKGROUND & AIMS: There have been increasing reports of liver injury associated with use of herbal and dietary supplements, likely due to easy access to these products and beliefs among consumers that they are safer or more effective than conventional medications. We aimed to evaluate clinical features and outcomes of patients with herbal and dietary supplement-induced liver injuries included in the Spanish DILI Registry. METHODS: We collected and analyzed data on demographic and clinical features, along with biochemical parameters, of 32 patients with herbal and dietary supplement-associated liver injury reported to the Spanish DILI registry from 1994 through 2016...
January 4, 2018: Clinical Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29306044/heavy-consumption-of-alcohol-is-not-associated-with-worse-outcomes-in-patients-with-idiosyncratic-drug-induced-liver-injury-compared-to-non-drinkers
#16
Lara Dakhoul, Marwan Ghabril, Jiezhun Gu, Victor Navarro, Naga Chalasani, Jose Serrano
BACKGROUND & AIMS: The relationship between alcohol consumption and idiosyncratic drug induced liver injury (DILI) is not well understood. We investigated the relationship between heavy consumption of alcohol and characteristics and outcomes of patients with DILI enrolled in the Drug-induced Liver Injury Network (DILIN) prospective study. METHODS: We collected data from 1198 individuals with definite, highly likely, or probable DILI enrolled in the DILIN study from September 2004 through April 2016...
January 3, 2018: Clinical Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29296203/the-pathogenesis-of-diclofenac-induced-immunoallergic-hepatitis-in-a-canine-model-of-liver-injury
#17
Saravanakumar Selvaraj, Jung-Hwa Oh, Reinhard Spanel, Florian Länger, Hyoung-Yun Han, Eun-Hee Lee, Seokjoo Yoon, Jürgen Borlak
Hypersensitivity to non-steroidal anti-inflammatory drugs is a common adverse drug reaction and may result in serious inflammatory reactions of the liver. To investigate mechanism of immunoallergic hepatitis beagle dogs were given 1 or 3 mg/kg/day (HD) oral diclofenac for 28 days. HD diclofenac treatment caused liver function test abnormalities, reduced haematocrit and haemoglobin but induced reticulocyte, WBC, platelet, neutrophil and eosinophil counts. Histopathology evidenced hepatic steatosis and glycogen depletion, apoptosis, acute lobular hepatitis, granulomas and mastocytosis...
December 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/29287080/serum-apolipoprotein-a1-and-haptoglobin-in-patients-with-suspected-drug-induced-liver-injury-dili-as-biomarkers-of-recovery
#18
Valentina Peta, Chantal Tse, Hugo Perazzo, Mona Munteanu, Yen Ngo, An Ngo, Nittia Ramanujam, Lea Verglas, Maxime Mallet, Vlad Ratziu, Dominique Thabut, Marika Rudler, Vincent Thibault, Ina Schuppe-Koistinen, Dominique Bonnefont-Rousselot, Bernard Hainque, Françoise Imbert-Bismut, Michael Merz, Gerd Kullak-Ublick, Raul Andrade, Florian van Boemmel, Eckart Schott, Thierry Poynard
BACKGROUND: There is a clear need for better biomarkers of drug-induced-liver-injury (DILI). AIMS: We aimed to evaluate the possible prognostic value of ActiTest and FibroTest proteins apoliprotein-A1, haptoglobin and alpha-2-macroglobulin, in patients with DILI. METHODS: We analyzed cases and controls included in the IMI-SAFE-T-DILI European project, from which serum samples had been stored in a dedicated biobank. The analyses of ActiTest and FibroTest had been prospectively scheduled...
2017: PloS One
https://www.readbyqxmd.com/read/29278707/metformin-ameliorates-activation-of-hepatic-stellate-cells-and-hepatic-fibrosis-by-succinate-and-gpr91-inhibition
#19
Giang Nguyen, So Young Park, Cong Thuc Le, Won Sun Park, Dae Hee Choi, Eun-Hee Cho
BACKGROUND: Chronic liver disease is becoming a major cause of morbidity and mortality worldwide. During liver injury, hepatic stellate cells (HSCs) trans-differentiate into activated myofibroblasts, which produce extracellular matrix. Succinate and succinate receptor (G-protein coupled receptor91, GPR91) signaling pathway has now emerged as a regulator of metabolic signaling. A previous study showed that succinate and its specific receptor, GPR91, are involved in the activation of HSCs and the overexpression of α-smooth muscle actin (α-SMA)...
December 23, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29274889/new-onset-autoimmune-hepatitis-during-anti-tumor-necrosis-factor-alpha-treatment-in-children
#20
Amanda Ricciuto, Binita M Kamath, Thomas D Walters, Karen Frost, Nicholas Carman, Peter C Church, Simon C Ling, Anne M Griffiths
OBJECTIVES: To evaluate a large anti-tumor necrosis factor (TNF)-treated pediatric inflammatory bowel disease cohort for drug-induced liver injury (DILI) following presentation of an index case with suspected DILI with autoimmune features after infliximab exposure. To characterize the incidence, natural history, and risk factors for liver enzyme elevation with anti-TNF use. STUDY DESIGN: We reviewed the index case and performed a retrospective cohort study of 659 children receiving anti-TNF therapy between 2000 and 2015 at a tertiary pediatric inflammatory bowel disease center...
December 21, 2017: Journal of Pediatrics
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