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acetaminophen and acute hepatic failure

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https://www.readbyqxmd.com/read/29628888/licochalcone-a-upregulates-nrf2-antioxidant-pathway-and-thereby-alleviates-acetaminophen-induced-hepatotoxicity
#1
Hongming Lv, Qingfei Xiao, Junfeng Zhou, Haihua Feng, Guowen Liu, Xinxin Ci
Acetaminophen (APAP) overdose-induced fatal hepatotoxicity is majorly characterized by overwhelmingly increased oxidative stress while enhanced nuclear factor-erythroid 2-related factor 2 (Nrf2) is involved in prevention of hepatotoxicity. Although Licochalcone A (Lico A) upregulates Nrf2 signaling pathway against oxidative stress-triggered cell injury, whether it could protect from APAP-induced hepatotoxicity by directly inducing Nrf2 activation is still poorly elucidated. This study aims to explore the protective effect of Lico A against APAP-induced hepatotoxicity and its underlying molecular mechanisms...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29580866/pyruvate-dehydrogenase-complex-and-lactate-dehydrogenase-as-targets-for-therapy-of-acute-liver-failure
#2
Rosa Ferriero, Edoardo Nusco, Rossella De Cegli, Annamaria Carissimo, Giuseppe Manco, Nicola Brunetti-Pierri
BACKGROUND AND AIMS: Acute liver failure is a rapidly progressive deterioration of hepatic function resulting in high mortality and morbidity. Metabolic enzymes can translocate in the nucleus to regulate histone acetylation and gene expression. METHODS: Levels and activities of pyruvate dehydrogenase complex (PDHC) and lactate dehydrogenase (LDH) were evaluated in nuclear fractions of livers of mice exposed to various hepatotoxins including CD95-Ab, α-amanitin, and acetaminophen...
March 23, 2018: Journal of Hepatology
https://www.readbyqxmd.com/read/29560444/ethyl-pyruvate-attenuates-acetaminophen-induced-liver-injury-and-prevents-cellular-injury-induced-by-n-acetyl-p-benzoquinone-imine
#3
Minako Nagatome, Yuki Kondo, Daisuke Kadowaki, Yusuke Saishyo, Mitsuru Irikura, Tetsumi Irie, Yoichi Ishitsuka
Acetaminophen, a common analgesic/antipyretic, is a frequent cause of acute liver failure in Western countries. The development of an effective cure against acetaminophen hepatotoxicity is crucial. Ethyl pyruvate, an ethyl ester derivative of pyruvic acid, has been identified as a possible candidate against acetaminophen hepatotoxicity in animal experiments. However, the mode of the hepatoprotective action of ethyl pyruvate remains unclear. We examined the hepatoprotective effect of ethyl pyruvate against hepatocyte injury and oxidative stress in a mouse model of acetaminophen hepatotoxicity...
February 2018: Heliyon
https://www.readbyqxmd.com/read/29524531/gut-microbiota-mediates-diurnal-variation-of-acetaminophen-induced-acute-liver-injury-in-mice
#4
Shenhai Gong, Tian Lan, Liyan Zeng, Haihua Luo, Xiaoyu Yang, Na Li, Xiaojiao Chen, Zhanguo Liu, Rui Li, Sanda Win, Shuwen Liu, Hongwei Zhou, Bernd Schnabl, Yong Jiang, Neil Kaplowitz, Peng Chen
BACKGROUND & AIMS: Acetaminophen (APAP) induced hepatotoxicity is a leading cause of acute liver failure worldwide. It is well established that the liver damage induced by acetaminophen exhibits diurnal variation. However, the detailed mechanism for the hepatotoxic variation is not clear. Here we aimed to determine the relative contributions of gut microbiota in modulating the diurnal variation of hepatotoxicity induced by APAP. METHODS: Male Balb/C mice were treated with or without antibiotics and orally administrated a single dose of APAP (300 mg/kg) at ZT0 (when the light is on-start of resting period) and ZT12 (when the light is off-start of active period)...
March 7, 2018: Journal of Hepatology
https://www.readbyqxmd.com/read/29504225/replicative-stress-and-alterations-in-cell-cycle-checkpoint-controls-following-acetaminophen-hepatotoxicity-restrict-liver-regeneration
#5
Preeti Viswanathan, Yogeshwar Sharma, Priya Gupta, Sanjeev Gupta
OBJECTIVES: Acetaminophen hepatotoxicity is a leading cause of hepatic failure with impairments in liver regeneration producing significant mortality. Multiple intracellular events, including oxidative stress, mitochondrial damage, inflammation, etc., signify acetaminophen toxicity, although how these may alter cell cycle controls has been unknown and was studied for its significance in liver regeneration. MATERIALS AND METHODS: Assays were performed in HuH-7 human hepatocellular carcinoma cells, primary human hepatocytes and tissue samples from people with acetaminophen-induced acute liver failure...
March 5, 2018: Cell Proliferation
https://www.readbyqxmd.com/read/29496991/non-invasive-imaging-of-drug-induced-liver-injury-with-18-f-dfa-pet
#6
Jessica R Salas, Bao Ying Chen, Alicia Wong, Sergio Duarte, Stephanie A K Angarita, Gerald S Lipshutz, Owen N Witte, Peter M Clark
Drug-induced liver failure is a significant indication for a liver transplant, and unexpected liver toxicity is a major reason that otherwise effective therapies are removed from the market. Various methods exist for monitoring liver injury but are often inadequate to predict liver failure. New diagnostic tools are needed. Methods: We evaluate in a preclinical model whether18 F-2-deoxy-2-fluoroarabinose (18 F-DFA), a PET radiotracer that measures the ribose salvage pathway, can be used to monitor acetaminophen-induced liver injury and failure...
March 1, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29473717/interventions-for-paracetamol-acetaminophen-overdose
#7
REVIEW
Angela L Chiew, Christian Gluud, Jesper Brok, Nick A Buckley
BACKGROUND: Paracetamol (acetaminophen) is the most widely used non-prescription analgesic in the world. Paracetamol is commonly taken in overdose either deliberately or unintentionally. In high-income countries, paracetamol toxicity is a common cause of acute liver injury. There are various interventions to treat paracetamol poisoning, depending on the clinical status of the person. These interventions include inhibiting the absorption of paracetamol from the gastrointestinal tract (decontamination), removal of paracetamol from the vascular system, and antidotes to prevent the formation of, or to detoxify, metabolites...
February 23, 2018: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/29461676/clinical-and-prognostic-associations-of-liver-volume-determined-by-computed-tomography-in-acute-liver-failure
#8
Abigail Zabron, Alberto Quaglia, Evangelia Fatourou, Praveen Peddu, Dylan Lewis, Michael Heneghan, Christopher Willars, Georg Auzinger, Nigel Heaton, Julia Wendon, Pauline Kane, John Karani, William Bernal
BACKGROUND: Liver volume (LV) can be non-invasively determined from analysis of computed tomography (CT) images, and in patients with Acute liver injury (ALI) or failure (ALF) reflect the balance of structural collapse with hepatic regeneration. We examined its relation to cause of liver injury, measures of liver function and histopathological findings, and utility in prediction of complications and mortality. METHODS: 273 patients with ALF/ALI admitted to a specialist intensive care unit were studied...
February 20, 2018: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/29454747/plasminogen-activator-inhibitor-1-reduces-tpa-dependent-fibrinolysis-and-intrahepatic-hemorrhage-in-experimental-acetaminophen-overdose
#9
Asmita Pant, Anna K Kopeć, Kevin S Baker, Holly Cline-Fedewa, Daniel A Lawrence, James P Luyendyk
Acetaminophen (APAP)-induced liver injury in mice is associated with activation of the coagulation cascade and deposition of fibrin in liver. Plasminogen activator inhibitor-1 (PAI-1) is an important physiological inhibitor of tissue-type plasminogen activator (tPA) and plays a critical role in fibrinolysis. PAI-1 expression is increased in both experimental APAP-induced liver injury and patients with acute liver failure. Prior studies have shown that PAI-1 prevents intrahepatic hemorrhage and mortality after APAP challenge, but the downstream mechanisms are not clear...
February 16, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29417856/gastrointestinal-safety-and-tolerability-of-oral-non-aspirin-over-the-counter-analgesics
#10
Nicholas Moore, James M Scheiman
Over-the-counter (OTC) analgesics are routinely used worldwide for self-management of various painful conditions. Despite this, there has been little in-depth review of the safety of non-aspirin analgesics at OTC doses. This paper reviews the available literature on the gastrointestinal (GI) and hepatic safety of non-aspirin OTC analgesics, including nonsteroidal anti-inflammatory drugs (NSAIDs; ibuprofen, ketoprofen, diclofenac, and naproxen) and acetaminophen; safety in overdose is also reviewed. Each non-aspirin OTC analgesic has a distinct adverse event (AE) profile, with GI AE rates for OTC dosing in one study ranging from 37% for diclofenac to 7...
February 8, 2018: Postgraduate Medicine
https://www.readbyqxmd.com/read/29388410/-high-anion-gap-metabolic-acidosis-pyroglutamic-acidosis-induced-by-chronic-acetaminophen-use
#11
J Tchougang Nono, V Mistretta, I Noirot, J L Canivet, P Damas
Acetaminophen is the most consumable analgesic in the world in the form of medical prescription or self-medication. It is one of the active ingredients most often involved in voluntary poisoning. Lethal dose of acetaminophen classically induces acute hepatic failure on hepatic necrosis. Chronic intake of sub-lethal doses (i.e. near recommended therapeutic doses) of acetaminophen in the presence of certain risk factors may be responsible for another much less recognized pathological manifestation: severe metabolic acidosis with an increased anion gap due to the accumulation of 5-oxoproline or pyroglutamic acid...
January 2018: Revue Médicale de Liège
https://www.readbyqxmd.com/read/29364842/natural-dietary-pigments-potential-mediators-against-hepatic-damage-induced-by-over-the-counter-non-steroidal-anti-inflammatory-and-analgesic-drugs
#12
REVIEW
Herson Antonio González-Ponce, Ana Rosa Rincón-Sánchez, Fernando Jaramillo-Juárez, Han Moshage
Over-the-counter (OTC) analgesics are among the most widely prescribed and purchased drugs around the world. Most analgesics, including non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen, are metabolized in the liver. The hepatocytes are responsible for drug metabolism and detoxification. Cytochrome P450 enzymes are phase I enzymes expressed mainly in hepatocytes and they account for ≈75% of the metabolism of clinically used drugs and other xenobiotics. These metabolic reactions eliminate potentially toxic compounds but, paradoxically, also result in the generation of toxic or carcinogenic metabolites...
January 24, 2018: Nutrients
https://www.readbyqxmd.com/read/29325178/modulation-of-o-glcnac-levels-in-the-liver-impacts-acetaminophen-induced-liver-injury-by-affecting-protein-adduct-formation-and-glutathione-synthesis
#13
Steven R McGreal, Bharat Bhushan, Chad Walesky, Mitchell R McGill, Margitta Lebofsky, Sylvie E Kandel, Robert D Winefield, Hartmut Jaeschke, Natasha E Zachara, Zhen Zhang, Ee Phie Tan, Chad Slawson, Udayan Apte
Overdose of acetaminophen (APAP) results in acute liver failure. We have investigated the role of a posttranslational modification of proteins called O-GlcNAcylation, where the O-GlcNAc transferase (OGT) adds and O-GlcNAcase (OGA) removes a single β-D-N-acetylglucosamine (O-GlcNAc) moiety, in the pathogenesis of APAP-induced liver injury. Hepatocyte-specific OGT knockout mice (OGT KO), which have reduced O-GlcNAcylation, and wild-type (WT) controls were treated with 300 mg/kg APAP and the development of injury was studied over a time course from 0 to 24 h...
April 1, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29243082/dihydroquercetin-ameliorated-acetaminophen-induced-hepatic-cytotoxicity-via-activating-jak2-stat3-pathway-and-autophagy
#14
Wenjing Zai, Wei Chen, Jingyun Luan, Jiajun Fan, Xuyao Zhang, Zimei Wu, Tao Ding, Dianwen Ju, Hongrui Liu
Acetaminophen (APAP) overdose is currently the leading cause of acute liver disease, but therapeutic treatment strategies are commonly limited. Although dihydroquercetin (DHQ) is an attractive botanical antioxidant, its protective potential for liver disease remains elusive. The present study investigated the protective effects of DHQ against APAP-induced hepatic cytotoxicity. Primary mouse hepatocytes were treated with different concentrations of DHQ followed by APAP administration. Our data showed that DHQ relieved APAP-induced growth inhibition and lactate dehydrogenase (LDH) release in a dose-dependent manner, as well as inhibited APAP-induced necrosis and extracellular signal regulated kinase-c-Jun-N-terminal kinase (ERK-JNK) stress...
February 2018: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29199145/acetaminophen-induced-acute-liver-failure-is-more-common-and-more-severe-in-women
#15
Jessica B Rubin, Bilal Hameed, Michelle Gottfried, William M Lee, Monika Sarkar
BACKGROUND & AIMS: Acetaminophen overdose is the leading cause of acute liver injury (ALI) and acute liver failure (ALF) in the developed world. Sex differences in acetaminophen-induced hepatotoxicity have not been described. METHODS: We collected data from the Acute Liver Failure Study Group cohort, a national registry of 32 academic medical centers in North America of adults with ALI or ALF, including 1162 patients with acetaminophen-induced ALI (n=250) or acetaminophen-induced ALF (n=912) from January 2000 through September 2016...
November 30, 2017: Clinical Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29174983/comparison-of-hepatic-transcriptome-profiling-between-acute-liver-injury-and-acute-liver-failure-induced-by-acetaminophen-in-mice
#16
COMPARATIVE STUDY
Chunmin Li, Yanan Ming, Wenting Hong, Yingyue Tang, Xiaohong Lei, Xiaobo Li, Yimin Mao
Acetaminophen (APAP) overdose is a leading cause of drug-induced acute liver failure in many countries. In the present study, we developed stable mouse models of acute drug-induced hepatic injury (DILI) and acute drug-induced hepatic failure (DILF) by sub-lethal and lethal APAP injection respectively. The differences in hepatic transcriptome profiling between these two models were compared by RNA sequencing, which were validated by qPCR, western-blot and ELISA. In results, serum IL-6, TNF-a and IL-10 levels are higher in DILF than in DILI...
February 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29088996/aggressive-treatment-of-life-threatening-hypophosphatemia-during-recovery-from-fulminant-hepatic-failure-a-case-report
#17
Brittany D Bissell, Jason E Davis, Alexander H Flannery, David A Adkins, Melissa L Thompson Bastin
Acute liver failure secondary to acetaminophen overdose can be a life-threatening condition, characterized by severe electrolyte derangements. Hepatocyte regeneration is associated with phosphorous utilization and is a known complication of liver recovery following injury. We report the case of profound, life-threatening hypophosphatemia following recovery from acute fulminant liver failure. As the liver enzymes normalized, serum phosphorous levels plummeted. Our patient required an aggressive, individualized phosphorus replacement regimen, which resulted in a continuous infusion of intravenous (IV) sodium phosphate, titrated to a maximum rate of 30 mmol/h or 0...
January 1, 2017: Journal of Intensive Care Medicine
https://www.readbyqxmd.com/read/28986131/selenoprotein-msrb1-deficiency-exacerbates-acetaminophen-induced-hepatotoxicity-via-increased-oxidative-damage
#18
Ki Young Kim, Geun-Hee Kwak, Mahendra Pratap Singh, Vadim N Gladyshev, Hwa-Young Kim
Acetaminophen (APAP) overdose induces acute liver damage and failure via reactive oxygen species production and glutathione (GSH) depletion. Methionine sulfoxide reductase B1 (MsrB1) is an antioxidant selenoenzyme that specifically catalyzes the reduction of methionine R-sulfoxide residues. In this study, we used MsrB1 gene-knockout mice and primary hepatocytes to investigate the effect of MsrB1 on APAP-induced hepatotoxicity. Analyses of histological alterations and serum indicators of liver damage showed that MsrB1-/- mice were more susceptible to APAP-induced acute liver injury than wild-type (MsrB1+/+ ) mice...
November 15, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28874859/editorial-severe-acute-liver-injury-cause-connects-to-outcome
#19
EDITORIAL
Curtis K Argo, Stephen H Caldwell
Severe acute liver injury (ALI) is a common condition with little objective study of its natural history and outcomes. In this paper by Koch et al. and the Acute Liver Failure (ALF) Study Group, the authors utilize a consensus definition of ALI requiring newly elevated bilirubin, alanine aminotransferase (ALT), and international normalized ration (INR) without evidence of hepatic encephalopathy (HE), with HE as the key differentiator of ALI from ALF. They show significantly higher rates of progression to ALF, liver transplantation, or death in non-acetaminophen etiologies of ALI...
September 2017: American Journal of Gastroenterology
https://www.readbyqxmd.com/read/28795995/toxic-myocarditis-caused-by-acetaminophen-in-a-multidrug-overdose
#20
Maxime Gosselin, Yann Dazé, Pascal Mireault, Marie Crahes
We report the case of an 18-year-old woman with personality disorders who was hospitalized a few hours after suicidal ingestion of acetaminophen, quetiapine, acetylsalicylic acid, and ethanol. Twelve hours after admission, severe liver damage was evident, but the patient was stable and awaiting hepatic transplantation. Electrolytes were successfully controlled. The condition of the liver stabilized. Cardiac biomarkers then deteriorated unexpectedly. Localized ST-segment elevations were noted on electrocardiogram, but angiography ruled out myocardial infarction...
December 2017: American Journal of Forensic Medicine and Pathology
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