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drug-induced liver injury

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https://www.readbyqxmd.com/read/28944883/baicalein-protects-tert%C3%A2-butyl-hydroperoxide%C3%A2-induced-hepatotoxicity-dependent-of-reactive-oxygen-species-removal
#1
Ya-Fang Wang, Zheng-Hai Tang, Ting Li, Xiao-Huang Xu, Xiuping Chen, Ying Wang, Yi-Tao Wang, Jin-Jian Lu
Baicalein (BA), one of the major bioactive flavonoids isolated from Scutellariae Radix, possesses various pharmacological activities. The present study aimed to investigate the protective effects of BA on tert‑butyl hydroperoxide (t‑BHP)‑induced hepatotoxicity, and to investigate the potential mechanisms in LO2 cells. BA was demonstrated to possess protective properties against t‑BHP injury in LO2 cells, as evidenced by MTT and lactate dehydrogenase assays. BA significantly prevented t‑BHP‑induced depolarization of mitochondrial membrane potential (MMP), decreased the percentage of apoptotic cells caused by t‑BHP, and prevented intracellular reactive oxygen species (ROS) generation in LO2 cells...
September 22, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28944052/the-role-of-the-hepatopathologist-in-the-assessment-of-drug-induced-liver-injury
#2
David E Kleiner
No abstract text is available yet for this article.
February 2017: Clinical Liver Disease
https://www.readbyqxmd.com/read/28942002/long-enduring-primary-hepatocyte-based-co-cultures-improve-prediction-of-hepatotoxicity
#3
Eric I Novik, Jacquelyn Dwyer, James K Morelli, Amit Parekh, Cheul Cho, Eitan Pludwinski, Anil Shrirao, Robert M Freedman, James S MacDonald, Zaid Jayyosi
The failure of drug candidates during clinical trials and post-marketing withdrawal due to Drug Induced Liver Injury (DILI), results in significant late-stage attrition in the pharmaceutical industry. Animal studies have proven insufficient to definitively predict DILI in the clinic, therefore a variety of in vitro models are being tested in an effort to improve prediction of human hepatotoxicity. The model system described here consists of cryopreserved primary rat, dog or human hepatocytes co-cultured together with a fibroblast cell line, which aids in the hepatocytes' maintenance of more in vivo-like characteristics compared to traditional hepatic mono-cultures, including long term viability and retention of activity of cytochrome P450 isozymes...
September 20, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28939132/peak-hyperammonemia-and-atypical-acute-liver-failure-the-eruption-of-an-urea-cycle-disorder-during-hyperemesis-gravidarum
#4
REVIEW
Nicolas Weiss, Fanny Mochel, Marika Rudler, Sophie Demeret, Pascal Lebray, Filomena Conti, Damien Galanaud, Chris Ottolenghi, Jean-Paul Bonnefont, Marc Dommergues, Jacques Bernuau, Dominique Thabut
BACKGROUND: Inborn urea cycle deficiencies are under-recognized metabolic causes of hyperammonaemia in adults. METHODS: A 28-year-old primigravida, 7-week pregnant woman affected by hyperemesis gravidarum developed acute liver injury and then acute liver failure (ALF) in less than 48 hours. RESULTS: Because the patient developed atypical features, especially mildly elevated serum transaminases contrasting with very high blood ammonia levels (281 μmol/l), concomitant with normal serum creatinine, an inborn error of metabolism was suspected...
September 19, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28934901/association-of-ugt2b7-polymorphisms-with-risk-of-induced-liver-injury-by-anti-tuberculosis-drugs-in-chinese-han
#5
Guo Chen, Shou-Quan Wu, Mei Feng, Yu Wang, Jing-Can Wu, Gui-Yi Ji, Miao-Miao Zhang, Qian-Qian Liu, Jian-Qing He
Anti-tuberculosis drug-induced liver injury (ATLI) is common during the treatment of tuberculosis (TB). As an important enzyme in the metabolism of many drugs, UGT2B7 (uridine diphosphate glucuronyl transferase 2B7) was associated with drug-induced liver disorder. This study investigated the association between the polymorphisms of UGT2B7 and ATLI in Chinese Han. Totally, 280 newly diagnosed TB patients had been followed up for 3 months after the prescription of anti-TB therapy. Tag-single-nucleotide polymorphism (tag-SNPs) (rs10028494 and rs7668282) were genotyped with the MassARRAY platform...
September 1, 2017: International Journal of Immunopathology and Pharmacology
https://www.readbyqxmd.com/read/28934748/severe-drug-induced-liver-injury-as-an-adverse-drug-event-of-antibiotics-a-case-report-and-review-of-the-literature
#6
Martin Munz, Hans Grummich, Josef Birkmann, Martin Wilhelm, Ulrike Holzgrabe, Fritz Sörgel
Drug-induced liver injury is one of the main reasons for acute liver failure. We report the case of a young patient who experienced a drug-induced liver injury resulting in life-threatening acute liver failure after treatment with different antibiotics (amoxicillin, ciprofloxacin, cefazolin, clindamycin) and acetaminophen, or a combination of these drugs. Moreover, we provide an overview of the hepatotoxic potential of these drugs.
September 22, 2017: Chemotherapy
https://www.readbyqxmd.com/read/28934241/hla-dr7-and-hla-dq2-transgenic-mouse-strains-tested-as-a-model-system-for-ximelagatran-hepatotoxicity
#7
Hanna Lundgren, Klara Martinsson, Karin Cederbrant, Johan Jirholt, Daniel Mucs, Katja Madeyski-Bengtson, Said Havarinasab, Per Hultman
The oral thrombin inhibitor ximelagatran was withdrawn in the late clinical trial phase because it adversely affected the liver. In approximately 8% of treated patients, drug-induced liver injury (DILI) was expressed as transient alanine transaminase (ALT) elevations. No evidence of DILI had been revealed in the pre-clinical in vivo studies. A whole genome scan study performed on the clinical study material identified a strong genetic association between the major histocompatibility complex alleles for human leucocyte antigens (HLA) (HLA-DR7 and HLA-DQ2) and elevated ALT levels in treated patients...
2017: PloS One
https://www.readbyqxmd.com/read/28933413/the-role-of-the-nrf2-are-antioxidant-system-in-preventing-cardiovascular-diseases
#8
REVIEW
Robert E Smith, Kevin Tran, Cynthia C Smith, Miranda McDonald, Pushkar Shejwalkar, Kenji Hara
It is widely believed that consuming foods and beverages that have high concentrations of antioxidants can prevent cardiovascular diseases and many types of cancer. As a result, many articles have been published that give the total antioxidant capacities of foods in vitro. However, many antioxidants behave quite differently in vivo. Some of them, such as resveratrol (in red wine) and epigallocatechin gallate or EGCG (in green tea) can activate the nuclear erythroid-2 like factor-2 (Nrf2) transcription factor...
November 11, 2016: Diseases (Basel)
https://www.readbyqxmd.com/read/28933119/-research-on-rat-models-of-acute-liver-injury-with-syndrome-of-liver-depression-and-spleen-deficiency
#9
Na-Na Huang, Xiao-Qian Sun, Qian Yang, Xiao-Yu Li, Rong Sun
This paper aimed to establish animal models which are suitable for the activity found, efficacy evaluation of herbs resistant to acute liver injury with syndrome of liver depression and spleen deficiency and new drug research and development based on corresponding of formula and syndrome. The symptoms that are suitable for evaluating the rat models of acute liver injury with syndrome of liver depression and spleen deficiency were extracted according to the evolution rule of the etiology and pathogenesis in traditional Chinese medicine and the modern pathological mechanism...
December 2016: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/28931315/the-liver-toxicity-knowledge-base-lktb-and-drug-induced-liver-injury-dili-classification-for-assessment-of-human-liver-injury
#10
Shraddha Thakkar, Weida Tong, Minjun Chen, Hong Fang, Zhichao Liu, Ruth Roberts
Drug-induced liver injury (DILI) is challenging drug development, clinical practice and regulation. The Liver Toxicity Knowledge Base (LTKB) provides essential data for DILI study. Areas Covered: The LTKB provided various types of data that can be used to assess and predict DILI. Among much information available, several reference drug lists with annotated human DILI risk are of important. The LTKB DILI classification data include DILI severity concern determined by the FDA drug labeling, DILI severity score from the NIH LiverTox database, and other DILI classification schemes from the literature...
September 21, 2017: Expert Review of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28930961/impact-of-a-novel-phosphoinositol-3-kinase-inhibitor-in-preventing-mitochondrial-dna-damage-and-damage-associated-molecular-pattern-accumulation-results-from-the-biochronicity-project
#11
George Edward Black, Kyle K Sokol, Donald M Moe, Jon D Simmons, David Muscat, Victor Pastukh, Gina Capley, Olena Gorodnya, Mykhaylo Ruchko, Mark B Roth, Mark Gillespie, Matthew J Martin
BACKGROUND: Despite improvements in the management of severely injured patients, development of multiple organ dysfunction syndrome (MODS) remains a morbid complication of traumatic shock. One of the key attributes of MODS is a profound bioenergetics crisis, for which the mediators and mechanisms are poorly understood. We hypothesized that metabolic uncoupling using an experimental phosphoinositol-3 kinase (PI3-K) inhibitor, LY294002 (LY), may prevent mitochondrial abnormalities that lead to the generation of mitochondrial DNA (mtDNA) damage and the release of mtDNA damage-associated molecular patterns (DAMPs)...
October 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/28930172/rhein-induces-oxidative-stress-and-apoptosis-in-mouse-blastocysts-and-has-immunotoxic-effects-during-embryonic-development
#12
Chien-Hsun Huang, Wen-Hsiung Chan
Rhein, a glucoside chemical compound found in a traditional Chinese medicine derived from the roots of rhubarb, induces cell apoptosis and is considered to have high potential as an antitumor drug. Several previous studies showed that rhein can inhibit cell proliferation and trigger mitochondria-related or endoplasmic reticulum (ER) stress-dependent apoptotic processes. However, the side effects of rhein on pre- and post-implantation embryonic development remain unclear. Here, we show that rhein has cytotoxic effects on blastocyst-stage mouse embryos and induces oxidative stress and immunotoxicity in mouse fetuses...
September 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28927656/features-and-outcomes-from-a-retrospective-study-of-570%C3%A2-hospitalized-chinese-patients-with-drug-induced-liver-injury
#13
Lili Pang, Wanna Yang, Fengqin Hou
AIMS: To investigate the clinical features and outcomes of hospitalized patients with drug-induced liver injury (DILI). METHODS: The medical records of hospitalized patients with DILI from January 1997 through July 2016 were reviewed. RESULTS: Five hundred seventy cases were reviewed, of which 381 (66.8%) were female. Four hundred fifty-eight cases (80.4%) presented with hepatocellular injury, 53 (9.3%) with cholestatic injury and 59 (10...
September 15, 2017: Clinics and Research in Hepatology and Gastroenterology
https://www.readbyqxmd.com/read/28925161/-protective-effects-of-liuwei-wuling-tablet-on-acute-alcoholic-induced-liver-injury-in-mice
#14
Ping Yin, He-Rong Cui, Cong-En Zhang, Yuan Zhang, Ya-Kun Meng, Lan-Zhi He, Hui-Min Liu, Xiu-Xiu Sang, Jia-Bo Wang, Zhao-Fang Bai, Xiao-He Xiao
The protective action and the relevant mechanism of Liuwei Wuling tablet on acute alcoholic hepatic injury in mice were investigated. All the C57BL/6 mice were divided randomly into 7 groups including blank, model, bifendate (150 mg•kg⁻¹, positive control) and experimental groups consisted of extremely low dose (0.1 g•kg⁻¹), low (0.5 g•kg⁻¹), upper (4 g•kg⁻¹) and high dose (8 g•kg⁻¹) of Liuwei Wuling tablet groups. The acute liver injury model was induced by modified method that the model, positive control and experimental groups were orally administrated 56% alcohol (6 g•kg⁻¹) twice at 12 hour intervals on the fifth day after drugs administration...
October 2016: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/28919711/protective-role-of-quercetin-against-manganese-induced-injury-in-the-liver-kidney-and-lung-and-hematological-parameters-in-acute-and-subchronic-rat-models
#15
Entaz Bahar, Geum-Hwa Lee, Kashi Raj Bhattarai, Hwa-Young Lee, Hyun-Kyoung Kim, Mallikarjun Handigund, Min-Kyung Choi, Sun-Young Han, Han-Jung Chae, Hyonok Yoon
Manganese (Mn) is an important mineral element required in trace amounts for development of the human body, while over- or chronic-exposure can cause serious organ toxicity. The current study was designed to evaluate the protective role of quercetin (Qct) against Mn-induced toxicity in the liver, kidney, lung, and hematological parameters in acute and subchronic rat models. Male Sprague Dawley rats were divided into control, Mn (100 mg/kg for acute model and 15 mg/kg for subchronic model), and Mn + Qct (25 and 50 mg/kg) groups in both acute and subchronic models...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28918124/polyphenols-reported-to-shift-apap-induced-changes-in-mapk-signaling-and-toxicity-outcomes
#16
REVIEW
Ngoc Uy Nguyen, Brendan David Stamper
Due to its widespread availability, acetaminophen (APAP) is the leading cause for drug-induced liver injury in many countries including United States and United Kingdom. When used as recommended, APAP is relatively safe. However, in overdose cases, increased metabolism of APAP to N-acetyl-para-benzoquinoneimine (NAPQI), a reactive metabolite, leads to glutathione (GSH) depletion, oxidative stress, and cellular injury. Throughout this process, a variety of factors play important roles in propagating toxicity, including c-Jun N-terminal kinase (JNK), a member of the mitogen-activated protein kinase (MAPK) family...
September 13, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28915221/metformin-exerts-beneficial-effects-in-hemorrhagic-shock-in-an-ampk%C3%AE-1-independent-manner
#17
Paul Kim, Giovanna Piraino, Michael O'Connor, Paul W Hake, Vivian Wolfe, Patrick Lahni, Basilia Zingarelli
Despite therapeutic advances in hemorrhagic shock, mortality from multiple organ failure remains high. AMP-activated protein kinase (AMPK) is involved in cellular energy homeostasis. Two catalytic subunits, α1 and α2, have been identified, with α1 subunit largely expressed in major organs. Here, we hypothesized that genetic deficiency of AMPKα1 worsens hemorrhage-induced multiple organ failure. We also investigated whether treatment with metformin, a clinically used drug for metabolic homeostasis, affords beneficial effects...
September 14, 2017: Shock
https://www.readbyqxmd.com/read/28912805/antifibrotic-effect-of-lactulose-on-a-methotrexate-induced-liver-injury-model
#18
Banu Taskin, Mümin Alper Erdoğan, Gürkan Yiğittürk, Damla Günenç, Oytun Erbaş
The most severe side effect of prolonged MTX treatment is hepatotoxicity. The aim of this study is to investigate the effect of lactulose treatment on MTX-induced hepatotoxicity in a rat model. Twenty-four male rats were included in the study. Sixteen rats were given a single dose of 20 mg/kg MTX to induce liver injury. Eight rats were given no drugs. 16 MTX-given rats were divided into two equal groups. Group 1 subjects were given lactulose 5 g/kg/day, and group 2 subjects were given saline 1 ml/kg/day for 10 days...
2017: Gastroenterology Research and Practice
https://www.readbyqxmd.com/read/28903847/dengue-hemorrhagic-fever-arare-cause-of-acute-liver-failure
#19
Aisha Nazeer, Ayesha Aslam Rai, Nasir Hassan Luck, Abbas Ali Yousuf Tasneem
Acute liver failure (ALF) is an acute medical emergency which carries high mortality without liver transplantation. Various hepatotropic viruses, drug induced liver injury, auto immune hepatitis, and metabolic liver diseases are the commonly implicated etiologic agents. Liver involvement in dengue hemorrhagic fever (DHF) is quite common, but acute liver failure is its rare complication. Neurological complications are also commonly seen in DHF. Ateenage girl presented with high grade fever and subconjunctival hemorrhage, and later developed jaundice due to acute liver failure...
August 2017: Journal of the College of Physicians and Surgeons—Pakistan: JCPSP
https://www.readbyqxmd.com/read/28895915/-autoimmune-like-drug-and-herb-induced-liver-injury-new-insights-into-molecular-pathogenesis
#20
REVIEW
Marcial Sebode, Lisa Schulz, Ansgar W Lohse
Idiosyncratic drug-induced liver injury (DILI) and hepatic injury due to herbal and dietary supplements (HDS) can adapt clinical characteristics of autoimmune hepatitis (AIH), such as the appearance of autoantibodies and infiltration of the liver by immune competent cells. To describe these cases of DILI/HDS, the poorly-defined term "autoimmune(-like)" DILI/HDS came up. It is uncertain if these cases represent a subgroup of DILI/HDS with distinct pathomechanistic and prognostic features different from "classical" DILI/HDS...
September 12, 2017: International Journal of Molecular Sciences
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