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Drug overdose liver failure

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https://www.readbyqxmd.com/read/27913221/role-of-the-inflammasome-in-acetaminophen-induced-liver-injury-and-acute-liver-failure
#1
REVIEW
Benjamin L Woolbright, Hartmut Jaeschke
Drug-induced acute liver failure carries a high morbidity and mortality rate. Acetaminophen overdose is the number one cause of acute liver failure and remains a major problem in Western medicine. Administration of N-acetyl cysteine is an effective antidote when given before the initial rise in toxicity; however, many patients present to the hospital after this stage occurs. As such, treatments which can alleviate late-stage acetaminophen-induced acute liver failure are imperative. While the initial mechanisms of toxicity are well described, a debate has occurred recently in the literature over whether or not there exists a second phase of injury, mediated by inflammatory processes...
November 29, 2016: Journal of Hepatology
https://www.readbyqxmd.com/read/27862262/different-effects-of-selective-%C3%AE-1-adrenoceptor-antagonists-nebivolol-or-atenolol-in-acetaminophen-induced-heptatotoxicity-of-rats
#2
Remon R Rofaeil, Maha Yehia Kamel, Walaa Yehia Abdelzaher
Acetaminophen (APAP) overdose is a common cause of acute liver failure and beta blockers are commonly used drugs in clinical practice. This study aims to evaluate the effect of two different beta blockers agents as nebivolol and atenolol against APAP-induced hepatotoxicity. Male wistar rats were treated with APAP (2 g/kg/day, p.o.) to induce hepatotoxicity. Our results showed that nebivolol and atenolol reduced heart rate and blood pressure. Nebivolol (5 mg/kg /day, p.o.) for 14 days has a hepatoprotective effect shown by significant decrease in hepatic injury parameters (serum AST and ALT) with significant suppression of hepatic malondialdehyde (MDA) and nitric oxide (NO) which were elevated with APAP administration...
November 14, 2016: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/27861792/drug-induced-liver-injury-advances-in-mechanistic-understanding-that-will-inform-risk-management
#3
Merrie Mosedale, Paul B Watkins
Drug-induced liver injury (DILI) is a major public health problem. Intrinsic (dose-dependent) DILI associated with acetaminophen overdose is the number one cause of acute liver failure in the US. However the most problematic type of DILI impacting drug development is idiosyncratic, occurring only very rarely among treated patients and often only after several weeks or months of treatment with the offending drug. Recent advances in our understanding of the pathogenesis of DILI suggest that three mechanisms may underlie the hepatocyte effects in response to both intrinsic and idiosyncratic DILI drugs: mitochondrial dysfunction, oxidative stress, and alterations in bile acid homeostasis...
November 9, 2016: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/27562556/editor-s-highlight-metformin-protects-against-acetaminophen-hepatotoxicity-by-attenuation-of-mitochondrial-oxidant-stress-and-dysfunction
#4
Kuo Du, Anup Ramachandran, James L Weemhoff, Hemantkumar Chavan, Yuchao Xie, Partha Krishnamurthy, Hartmut Jaeschke
Overdose of acetaminophen (APAP) causes severe liver injury and even acute liver failure in both mice and human. A recent study by Kim et al. (2015, Metformin ameliorates acetaminophen hepatotoxicity via Gadd45β-dependent regulation of JNK signaling in mice. J. Hepatol. 63, 75-82) showed that metformin, a first-line drug to treat type 2 diabetes mellitus, protected against APAP hepatotoxicity in mice. However, its exact protective mechanism has not been well clarified. To investigate this, C57BL/6J mice were treated with 400 mg/kg APAP and 350 mg/kg metformin was given 0...
December 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/27479586/detection-of-acetaminophen-protein-adducts-in-decedents-with-suspected-opioid-acetaminophen-combination-product-overdose
#5
Karen C Thomas, Diana G Wilkins, Steven C Curry, Todd C Grey, David M Andrenyak, Lawrence D McGill, Douglas E Rollins
Acetaminophen overdose is a leading cause of drug-induced liver failure in the United States. Acetaminophen-protein adducts have been suggested as a biomarker of hepatotoxicity. The purpose of this study was to determine whether protein-derived acetaminophen-protein adducts are quantifiable in postmortem samples. Heart blood, femoral blood, and liver tissue were collected at autopsy from 22 decedents suspected of opioid-acetaminophen overdose. Samples were assayed for protein-derived acetaminophen-protein adducts, acetaminophen, and selected opioids found in combination products containing acetaminophen...
September 2016: Journal of Forensic Sciences
https://www.readbyqxmd.com/read/27316915/french-intensive-care-society-international-congress-r%C3%A3-animation-2016
#6
(no author information available yet)
No abstract text is available yet for this article.
June 2016: Annals of Intensive Care
https://www.readbyqxmd.com/read/27280194/dasabuvir-exviera-only-assessed-as-part-of-a-difficult-to-manage-combination-in-hepatitis-c
#7
(no author information available yet)
In late 2015, the first-choice treatment for patients with chronic hepatitis C due to a genotype 1 virus (HCV-1) was the combination of ledipasvir (an NS5A protein inhibitor) + sofosbuvir (a nucleotide inhibitor of NS5B RNA polymerase), despite major uncertainties regarding its adverse effects. This combination is almost always virologically effective. Dasabuvir is a non-nucleoside inhibitor of the viral RNA polymerase NS5B. It is authorised in the EU for the treatment of patients with chronic hepatitis C due to HCV-1, usually combined with the fixed-dose combination (Viekirax) of ombitasvir (an HCV NS5A protein inhibitor) + paritaprevir (an HCV protease inhibitor) + ritonavir (to enhance paritaprevir bioavailability)...
May 2016: Prescrire International
https://www.readbyqxmd.com/read/27275268/fulminate-hepatic-failure-in-a-5-year-old-female-after-inappropriate-acetaminophen-treatment
#8
Irena Kasmi, Sashenka Sallabanda, Gentian Kasmi
BACKGROUND: Acetaminophen is a drug widely used in children because of its safety and efficacy. Although the risk of its toxicity is lower in children such reactions occur in pediatric patients from intentional overdoses and less frequently attributable to unintended inappropriate dosing. The aim of reporting this case is to attract the attention to the risk of the acetaminophen toxicity when administered in high doses. CASE PRESENTATION: We report here a 5 year old girl who developed fulminate liver failure with renal impairment and acute pancreatitis, as a result of acetaminophen toxicity caused from unintentional repeated supratherapeutic ingestion, with a total administered dose of 4800 mg in three consecutive days, 1600 mg/day, approximately 90 mg/kg/day...
September 15, 2015: Open Access Macedonian Journal of Medical Sciences
https://www.readbyqxmd.com/read/27235652/-good-use-and-knowledge-of-paracetamol-acetaminophen-among-self-medicated-patients-prospective-study-in-community-pharmacies
#9
Anne-Elise Severin, Nadine Petitpain, Julien Scala-Bertola, Clotilde Latarche, Melissa Yelehe-Okouma, Paolo Di Patrizio, Pierre Gillet
Acetaminophen (paracetamol), the highest over-the-counter (OTC) selling drug in France, is also the first cause of acute hepatic failure. We aimed to assess the good use and the knowledge of acetaminophen in a setting of urban self-medicated patients. We conducted a prospective observational study in randomly selected community pharmacies of Metz (France) agglomeration. Patients coming to buy OTC acetaminophen for themselves or their family had to answer to an anonymous autoquestionnaire. Responses were individually and concomitantly analyzed through 3 scores: good use, knowledge and overdosage...
June 2016: Thérapie
https://www.readbyqxmd.com/read/27161439/model-based-contextualization-of-in-vitro-toxicity-data-quantitatively-predicts-in-vivo-drug-response-in-patients
#10
Christoph Thiel, Henrik Cordes, Isabel Conde, José Vicente Castell, Lars Mathias Blank, Lars Kuepfer
Understanding central mechanisms underlying drug-induced toxicity plays a crucial role in drug development and drug safety. However, a translation of cellular in vitro findings to an actual in vivo context remains challenging. Here, physiologically based pharmacokinetic (PBPK) modeling was used for in vivo contextualization of in vitro toxicity data (PICD) to quantitatively predict in vivo drug response over time by integrating multiple levels of biological organization. Explicitly, in vitro toxicity data at the cellular level were integrated into whole-body PBPK models at the organism level by coupling in vitro drug exposure with in vivo drug concentration-time profiles simulated in the extracellular environment within the organ...
May 9, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27144271/attenuating-oxidative-stress-by-paeonol-protected-against-acetaminophen-induced-hepatotoxicity-in-mice
#11
Yi Ding, Qing Li, Yuan Xu, Yuning Chen, Yue Deng, Feng Zhi, Ke Qian
Acetaminophen (APAP) overdose is the most frequent cause of drug-induced acute liver failure. The purpose of this study was to investigate whether paeonol protected against APAP-induced hepatotoxicity. Mice treated with paeonol (25, 50, 100 mg/kg) received 400 mg/kg acetaminophen intraperitoneally (i.p.) and hepatotoxicity was assessed. Pre-treatment with paeonol for 6 and 24 h ameliorated APAP-induced hepatic necrosis and significantly reduced the serum alanine aminotransferase (ALT) and aspartate transaminase (AST) levels in a dose-dependent manner...
2016: PloS One
https://www.readbyqxmd.com/read/27108714/plasma-paracetamol-concentration-at-hospital-presentation-has-a-dose-dependent-relationship-with-liver-injury-despite-prompt-treatment-with-intravenous-acetylcysteine
#12
David G Cairney, Hannah K S Beckwith, Khalid Al-Hourani, Michael Eddleston, D Nicholas Bateman, James W Dear
CONTEXT: Paracetamol (acetaminophen) overdose is a common reason for emergency hospital admission in the UK and the leading cause of acute liver failure in the Western world. Currently, the antidote acetylcysteine (NAC) is administered at a dose determined only by body weight without regard for the body burden of paracetamol. OBJECTIVE: To determine whether higher plasma paracetamol concentrations are associated with increased risk of liver injury despite prompt treatment with intravenous NAC...
June 2016: Clinical Toxicology
https://www.readbyqxmd.com/read/27057006/reducing-hepatocyte-injury-and-necrosis-in-response-to-paracetamol-using-noncoding-rnas
#13
Dagmara Szkolnicka, Baltasar Lucendo-Villarin, Joanna K Moore, Kenneth J Simpson, Stuart J Forbes, David C Hay
UNLABELLED: The liver performs multiple functions within the human body. It is composed of numerous cell types, which play important roles in organ physiology. Our study centers on the major metabolic cell type of the liver, the hepatocyte, and its susceptibility to damage during drug overdose. In these studies, hepatocytes were generated from a renewable and genetically defined resource. In vitro-derived hepatocytes were extensively profiled and exposed to varying levels of paracetamol and plasma isolated from liver-failure patients, with a view to identifying noncoding microRNAs that could reduce drug- or serum-induced hepatotoxicity...
June 2016: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/27017358/-a-prospective-study-on-suicide-attempts-by-self-poisoning-in-adolescents-symptoms-and-complications
#14
J Le Vaillant, L Pellerin, J Brouard, D Nimal-Cuvillon
AIM: Biological complications in adolescents' self-poisoning are not currently evaluated. The aim of this study was to describe the toxicological characteristics of suicide attempts, the ingested substances, and their complications to better prevent the risks associated with deliberate self-poisoning. MATERIALS AND METHODS: This was a descriptive, prospective, single-center study. It took place in the pediatric emergency, hospitalization, and intensive care unit of the Caen University Hospital...
May 2016: Archives de Pédiatrie: Organe Officiel de la Sociéte Française de Pédiatrie
https://www.readbyqxmd.com/read/26990366/remote-ischemic-conditioning-protects-against-acetaminophen-induced-acute-liver-injury-in-mice
#15
Wei Zheng, Zhiyong Zhang, Sushun Liu, Jianbin Bi, Jingyao Zhang, Lixue Du, Xiaoming Ding, Chang Liu
Acetaminophen (APAP) overdose is a major cause of drug acute liver failure. Studies have shown that remote ischemic pre- and post-conditioning (R-IPC and R-IPOST) can protect the liver against ischemia-reperfusion (I/R) and LPS induced injuries. The aim of this study was to investigate the effect of R-IPC and R-IPOST on APAP-induced hepatotoxicity in mice. Mice were randomized (n = 6 per group) to seven major groups that were treated as follows: (1) the normal control group; (2) the sham operated group; (3) the APAP group; (4) R-IPC + APAP group; (5) R-IPC + APAP + ZnPP group; (6) R-IPOST + APAP group; and (7) R-IPOST + APAP + ZnPP group...
March 17, 2016: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/26965985/glycyrrhizin-protects-against-acetaminophen-induced-acute-liver-injury-via-alleviating-tumor-necrosis-factor-%C3%AE-mediated-apoptosis
#16
Tingting Yan, Hong Wang, Min Zhao, Tomoki Yagai, Yingying Chai, Kristopher W Krausz, Cen Xie, Xuefang Cheng, Jun Zhang, Yuan Che, Feiyan Li, Yuzheng Wu, Chad N Brocker, Frank J Gonzalez, Guangji Wang, Haiping Hao
Acetaminophen (APAP) overdose is the leading cause of drug-induced acute liver failure in Western countries. Glycyrrhizin (GL), a potent hepatoprotective constituent extracted from the traditional Chinese medicine liquorice, has potential clinical use in treating APAP-induced liver failure. The present study determined the hepatoprotective effects and underlying mechanisms of action of GL and its active metabolite glycyrrhetinic acid (GA). Various administration routes and pharmacokinetics-pharmacodynamics analyses were used to differentiate the effects of GL and GA on APAP toxicity in mice...
May 2016: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/26955890/role-of-food-derived-antioxidant-agents-against-acetaminophen-induced-hepatotoxicity
#17
Dianelena Eugenio-Pérez, Héctor Adolfo Montes de Oca-Solano, José Pedraza-Chaverri
Context Acetaminophen (APAP), also known as paracetamol and N-acetyl p-aminophenol, is one of the most frequently used drugs for analgesic and antipyretic purposes on a worldwide basis. It is safe and effective at recommended doses but has the potential for causing hepatotoxicity and acute liver failure (ALF) with overdose. To solve this problem, different strategies have been developed, including the use of compounds isolated from food, which have been studied to characterize their efficacy as natural dietary antioxidants...
October 2016: Pharmaceutical Biology
https://www.readbyqxmd.com/read/26921661/acetaminophen-from-liver-to-brain-new-insights-into-drug-pharmacological-action-and-toxicity
#18
REVIEW
Carolina I Ghanem, María J Pérez, José E Manautou, Aldo D Mottino
Acetaminophen (APAP) is a well-known analgesic and antipyretic drug. It is considered to be safe when administered within its therapeutic range, but in cases of acute intoxication, hepatotoxicity can occur. APAP overdose is the leading cause of acute liver failure in the northern hemisphere. Historically, studies on APAP toxicity have been focused on liver, with alterations in brain function attributed to secondary effects of acute liver failure. However, in the last decade the pharmacological mechanism of APAP as a cannabinoid system modulator has been documented and some articles have reported "in situ" toxicity by APAP in brain tissue at high doses...
July 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/26721592/caffeic-acid-prevents-acetaminophen-induced-liver-injury-by-activating-the-keap1-nrf2-antioxidative-defense-system
#19
Chun Pang, Zhiyong Zheng, Liang Shi, Yuchen Sheng, Hai Wei, Zhengtao Wang, Lili Ji
UNLABELLED: Acute liver failure induced by acetaminophen (APAP) overdose is the main cause of drug-induced liver injury (DILI). Caffeic acid (CA) is a phenolic compound from many natural products. This study aims to investigate the protective mechanism of CA in APAP-induced liver injury. The results of serum alanine/aspartate aminotransferases (ALT/AST), liver myeloperoxidase (MPO) activity, liver glutathione (GSH) and reactive oxygen species (ROS) levels demonstrated the protection of CA against APAP-induced liver injury...
February 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/26680679/gab1-adaptor-protein-acts-as-a-gatekeeper-to-balance-hepatocyte-death-and-proliferation-during-acetaminophen-induced-liver-injury-in-mice
#20
Kunimaro Furuta, Yuichi Yoshida, Satoshi Ogura, Tomohide Kurahashi, Takashi Kizu, Shinichiro Maeda, Mayumi Egawa, Norihiro Chatani, Keigo Nishida, Yoshikazu Nakaoka, Shinichi Kiso, Yoshihiro Kamada, Tetsuo Takehara
UNLABELLED: Acetaminophen (APAP) overdose is the leading cause of drug-induced acute liver failure. In APAP-induced acute liver failure, hepatocyte death and subsequent liver regeneration determines the prognosis of patients, making it necessary to identify suitable therapeutic targets based on detailed molecular mechanisms. Grb2-associated binder 1 (Gab1) adaptor protein plays a crucial role in transmitting signals from growth factor and cytokine receptors to downstream effectors. In this study, we hypothesized that Gab1 is involved in APAP-induced acute liver failure...
April 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
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