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Acetaminophen toxicity

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https://www.readbyqxmd.com/read/28447858/risk-prediction-of-hepatotoxicity-in-paracetamol-poisoning
#1
Anselm Wong, Andis Graudins
CONTEXT: Paracetamol (acetaminophen) poisoning is the most common cause of acute liver failure in the developed world. A paracetamol treatment nomogram has been used for over four decades to help determine whether patients will develop hepatotoxicity without acetylcysteine treatment, and thus indicates those needing treatment. Despite this, a small proportion of patients still develop hepatotoxicity. More accurate risk predictors would be useful to increase the early detection of patients with the potential to develop hepatotoxicity despite acetylcysteine treatment...
April 27, 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28444411/-acute-liver-failure
#2
A Koch, C Trautwein, F Tacke
Acute liver failure (ALF) is a rare, but life-threatening disease that is characterized by the acute onset of jaundice, coagulopathy, and hepatic encephalopathy (HE) in patients without pre-existing liver disease. Main causes in Germany are drug toxicity, acetaminophen overdose, and viral hepatitis (A, B, E). For the initial assessment of patients with ALF and the diagnostic algorithm, the early detection of HE, exclusion of liver cirrhosis, immediate diagnosis of the underlying etiology, and evaluation for the necessity of liver transplantation (LT) are critical...
April 25, 2017: Medizinische Klinik, Intensivmedizin und Notfallmedizin
https://www.readbyqxmd.com/read/28442342/methionine-sulfoxide-reductase-a-protects-hepatocytes-against-acetaminophen-induced-toxicity-via-regulation-of-thioredoxin-reductase-1-expression
#3
Mahendra Pratap Singh, Geun-Hee Kwak, Ki Young Kim, Hwa-Young Kim
Thioredoxin reductase 1 (TXNRD1) is associated with susceptibility to acetaminophen (APAP)-induced liver damage. Methionine sulfoxide reductase A (MsrA) is an antioxidant and protein repair enzyme that specifically catalyzes the reduction of methionine S-sulfoxide residues. We have previously shown that MsrA deficiency exacerbates acute liver injury induced by APAP. In this study, we used primary hepatocytes to investigate the underlying mechanism of the protective effect of MsrA against APAP-induced hepatotoxicity...
April 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28421843/reply-to-limitations-of-the-evidence-supporting-use-of-undetectable-acetaminophen-levels-obtained-4%C3%A2-hours-post-ingestion-to-rule-out-toxicity
#4
Mark C Yarema, Marco L A Sivilotti, Alberto Nettel-Aguirre, Barry H Rumack
No abstract text is available yet for this article.
June 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28421840/limitations-of-the-evidence-supporting-use-of-undetectable-acetaminophen-levels-obtained-4%C3%A2-hours-post-ingestion-to-rule-out-toxicity
#5
Meghan B Spyres, Ayrn D O'Connor, Richard D Gerkin
No abstract text is available yet for this article.
June 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28416868/a-synergistic-effect-of-cremophor-and-beta-glucosylceramide-to-exert-liver-and-sugar-protection
#6
Yehudit Shabat, Yaron Ilan
Many commonly used drugs carry the potential to induce hepatotoxicity, and a large number of foods and beverages induce an increase in blood sugar levels. A change in lifestyle by omitting these compounds is not applicable in many circumstances. β-Glucosylceramide (GC) is a naturally occurring glycosphingolipid that exerts an effect on the immune system. Cremophor EL (CrEL) is a synthetic, nonionic surfactant that is used as a vehicle for the administration of water-insoluble compounds. The aim of the present study was to determine the synergistic effect of oral administration of the combination of GC and CrEL (GCC) when added to potential toxic substrates or to sugar-enriched compounds...
April 2017: Journal of Food Science and Technology
https://www.readbyqxmd.com/read/28410455/diallyl-polysulfides-from-allium-sativum-as-immunomodulators-hepatoprotectors-and-antimycobacterial-agents
#7
Carel Oosthuizen, Miriam Arbach, Debra Meyer, Chris Hamilton, Namrita Lall
Mycobacterium tuberculosis remains one of the world's deadliest killers, with an annual death rate of ∼1.5 million. The medicinal effects of garlic have been well documented, and natural products have been shown to have antimycobacterial activity. The current study evaluated the efficacy of six Allium sativum L. polysulfide mixtures as antimycobacterial agents together with their cytotoxic, immunomodulatory, and hepatoprotective activities. The microtitre PrestoBlue assay was used to determine the minimum inhibitory concentrations (MIC)...
April 14, 2017: Journal of Medicinal Food
https://www.readbyqxmd.com/read/28409533/control-of-oxygen-tension-recapitulates-zone-specific-functions-in-human-liver-microphysiology-systems
#8
Felipe T Lee-Montiel, Subin M George, Albert H Gough, Anup D Sharma, Juanfang Wu, Richard DeBiasio, Lawrence A Vernetti, D Lansing Taylor
This article describes our next generation human Liver Acinus MicroPhysiology System (LAMPS). The key demonstration of this study was that Zone 1 and Zone 3 microenvironments can be established by controlling the oxygen tension in individual devices over the range of ca. 3 to 13%. The oxygen tension was computationally modeled using input on the microfluidic device dimensions, numbers of cells, oxygen consumption rates of hepatocytes, the diffusion coefficients of oxygen in different materials and the flow rate of media in the MicroPhysiology System (MPS)...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28379590/hepatotoxicity-of-paracetamol-and-related-fatalities
#9
R Tittarelli, M Pellegrini, M G Scarpellini, E Marinelli, V Bruti, N M di Luca, F P Busardò, S Zaami
Paracetamol, also known as acetaminophen, is the most commonly used antipyretic and pain reliever and since 1955 it is available over-the-counter as a single formulation or in combination with other substances and, as indicated by the World Health Organization, it can be used in all the three steps of pain intensity. Paracetamol toxicity is one of the most common causes of poisoning worldwide. While paracetamol is described as relatively nontoxic when administered in therapeutic doses, it is known to cause toxicity when taken in a single or repeated high dose, or after chronic ingestion...
March 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28374970/human-bj-fibroblasts-is-an-alternative-to-mouse-balb-c-3t3-cells-in-in-vitro-neutral-red-uptake-assay
#10
Marika Mannerström, Tarja Toimela, Jertta-Riina Sarkanen, Tuula Heinonen
The OECD GD 129 BALB/c 3T3 Neutral Red Uptake (NRU) assay is a standardized test method for estimating starting dose for an acute oral systemic toxicity test in rodents. Mouse BALB/c 3T3 fibroblasts are the most commonly used cells in the NRU assay. We have previously transferred and validated BALB/c 3T3 NRU assay in our GLP laboratory. Subsequently, in order to obtain more human relevant cytotoxicity data, we performed an intra-laboratory validation using human BJ fibroblasts in the NRU assay instead of mouse BALB/c 3T3 fibroblasts...
April 4, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28359199/protective-effect-of-cymbopogon-citratus-essential-oil-in-experimental-model-of-acetaminophen-induced-liver-injury
#11
Nancy Sayuri Uchida, Saulo Euclides Silva-Filho, Rafael Pazinatto Aguiar, Luiz Alexandre Marques Wiirzler, Gabriel Fernando Esteves Cardia, Heitor Augusto Otaviano Cavalcante, Francielli Maria de Souza Silva-Comar, Tânia Cristina Alexandrino Becker, Expedito Leite Silva, Ciomar Aparecida Bersani-Amado, Roberto Kenji Nakamura Cuman
To investigate the hepatoprotective effect of Cymbopogon citratus or lemongrass essential oil (LGO), it was used in an animal model of acute liver injury induced by acetaminophen (APAP). Swiss mice were pretreated with LGO (125, 250 and 500[Formula: see text]mg/kg) and SLM (standard drug, 200[Formula: see text]mg/kg) for a duration of seven days, followed by the induction of hepatotoxicity of APAP (single dose, 250[Formula: see text]mg/kg). The liver function markers alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and gamma-glutamyl transferase were determined to evaluate the hepatoprotective effects of the LGO...
March 30, 2017: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/28336158/-acetaminophen-knowledge-use-and-overdose-risk-in-urban-patients-consulting-their-general-practitioner-a-prospective-descriptive-and-transversal-study
#12
Lauriane Cipolat, Ouriel Loeb, Clotilde Latarche, Elise Pape, Pierre Gillet, Nadine Petitpain
INTRODUCTION: Acetaminophen is the most involved active substance in both unintentional and intentional drug poisoning. However, its availability outside community pharmacies is being debated in France. METHODS: We made, via a self-administered questionnaire, a prospective assessment of knowledge, use and acetaminophen overdose risk in patients consulting their general practitioner, in the Metz Métropole urban area, between May 2015 and February 2016. We estimated the prevalence of potential unintentional overdosage by capture-recapture method...
February 20, 2017: Thérapie
https://www.readbyqxmd.com/read/28330995/hepatic-fcrn-regulates-albumin-homeostasis-and-susceptibility-to-liver-injury
#13
Michal Pyzik, Timo Rath, Timothy T Kuo, Sanda Win, Kristi Baker, Jonathan J Hubbard, Rosa Grenha, Amit Gandhi, Thomas D Krämer, Adam R Mezo, Zachary S Taylor, Kevin McDonnell, Vicki Nienaber, Jan Terje Andersen, Atsushi Mizoguchi, Laurence Blumberg, Shalaka Purohit, Susan D Jones, Greg Christianson, Wayne I Lencer, Inger Sandlie, Neil Kaplowitz, Derry C Roopenian, Richard S Blumberg
The neonatal crystallizable fragment receptor (FcRn) is responsible for maintaining the long half-life and high levels of the two most abundant circulating proteins, albumin and IgG. In the latter case, the protective mechanism derives from FcRn binding to IgG in the weakly acidic environment contained within endosomes of hematopoietic and parenchymal cells, whereupon IgG is diverted from degradation in lysosomes and is recycled. The cellular location and mechanism by which FcRn protects albumin are partially understood...
April 4, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28291796/the-effect-of-acetaminophen-on-ubiquitin-homeostasis-in-saccharomyces-cerevisiae
#14
Angelina Huseinovic, Jolanda S van Leeuwen, Tibor van Welsem, Iris Stulemeijer, Fred van Leeuwen, Nico P E Vermeulen, Jan M Kooter, J Chris Vos
Acetaminophen (APAP), although considered a safe drug, is one of the major causes of acute liver failure by overdose, and therapeutic chronic use can cause serious health problems. Although the reactive APAP metabolite N-acetyl-p-benzoquinoneimine (NAPQI) is clearly linked to liver toxicity, toxicity of APAP is also found without drug metabolism of APAP to NAPQI. To get more insight into mechanisms of APAP toxicity, a genome-wide screen in Saccharomyces cerevisiae for APAP-resistant deletion strains was performed...
2017: PloS One
https://www.readbyqxmd.com/read/28286920/blockade-of-notch-signaling-promotes-acetaminophen-induced-liver-injury
#15
Longfeng Jiang, Michael Ke, Shi Yue, Wen Xiao, Youde Yan, Xiaozhao Deng, Qi-Long Ying, Jun Li, Bibo Ke
Liver injury after experimental acetaminophen treatment is mediated both by direct hepatocyte injury through a P450-generated toxic metabolite and indirectly by activated liver Kupffer cells and neutrophils. This study was designed to investigate the role of Notch signaling in the regulation of innate immune responses in acetaminophen (APAP)-induced liver injury. Using a mouse model of APAP-induced liver injury, wild-type (WT) and toll-like receptor 4 knockout (TLR4 KO) mice were injected intraperitoneally with APAP or PBS...
March 13, 2017: Immunologic Research
https://www.readbyqxmd.com/read/28255555/procalcitonin-impairs-liver-cell-viability-and-function-in-vitro-a-potential-new-mechanism-of-liver-dysfunction-and-failure-during-sepsis
#16
Martin Sauer, Sandra Doß, Johannes Ehler, Thomas Mencke, Nana-Maria Wagner
Purpose. Liver dysfunction and failure are severe complications of sepsis and result in poor outcome and increased mortality. The underlying pathologic mechanisms of hepatocyte dysfunction and necrosis during sepsis are only incompletely understood. Here, we investigated whether procalcitonin, a biomarker of sepsis, modulates liver cell function and viability. Materials and Methods. Employing a previously characterized and patented biosensor system evaluating hepatocyte toxicity in vitro, human hepatocellular carcinoma cells (HepG2/C3A) were exposed to 0...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28253482/aav-nrf2-promotes-protection-and-recovery-in-animal-models-of-oxidative-stress
#17
Katharine J Liang, Kenton T Woodard, Mark A Weaver, John Paul Gaylor, Ellen R Weiss, R Jude Samulski
NRF2 is a transcription factor that drives antioxidant gene expression in multiple organ systems. We hypothesized that Nrf2 overexpression could be therapeutically applied toward diseases in which redox homeostasis is disrupted. In this study, adeno-associated virus (AAV)-Nrf2 was tested in a mouse model of acute acetaminophen-induced liver toxicity and successfully conferred protection from hepatotoxicity, validating the vector design and early onset of NRF2-mediated protection. Furthermore, therapeutic potential of AAV-Nrf2 in chronic disease also was tested in a light-induced mouse model of age-related macular degeneration...
March 1, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28246565/diphenhydramine-as-a-cause-of-drug-induced-liver-injury
#18
Yunseok Namn, Yecheskel Schneider, Isabelle H Cui, Arun Jesudian
Drug-induced liver injury (DILI) is the most common cause of acute liver failure in the Unites States and accounts for 10% of acute hepatitis cases. We report the only known case of diphenhydramine-induced acute liver injury in the absence of concomitant medications. A 28-year-old man with history of 13/14-chromosomal translocation presented with fevers, vomiting, and jaundice. Aspartate-aminotransferase and alanine-aminotransferase levels peaked above 20,000 IU/L and 5,000 IU/L, respectively. He developed coagulopathy but without altered mental status...
2017: Case Reports in Hepatology
https://www.readbyqxmd.com/read/28246450/protective-effect-of-rutin-in-comparison-to-silymarin-against-induced-hepatotoxicity-in-rats
#19
M Kasi Reddy, A Gopala Reddy, B Kala Kumar, D Madhuri, G Boobalan, M Anudeep Reddy
AIM: The aim of this study is to evaluate the hepatoprotective effect of rutin (RTN) in comparison to silymarin (SLM) against acetaminophen (APAP)-induced hepatotoxicity in rats. MATERIALS AND METHODS: Male Wistar albino rats (n=24) of 3 months age were equally divided into four groups. Group 1 served as normal control. Hepatotoxicity was induced in the remaining three groups with administration of 500 mg/kg po APAP from day 1-3. Groups 2, 3, and 4 were subsequently administered orally with distilled water, 25 mg/kg of SLM, and 20 mg/kg of RTN, respectively, for 11 days...
January 2017: Veterinary World
https://www.readbyqxmd.com/read/28219592/urgent-liver-transplantation-for-dietary-supplements-an-under-recognized-problem
#20
L L Wong, L Lacar, M Roytman, S L Orloff
BACKGROUND: The recent outbreak of acute liver failure caused by herbal/dietary supplements (HDS) in Hawaii prompted evaluation of those patients who underwent emergency liver transplantation (LT) for HDS in the United States. METHODS: We queried the Scientific Registry of Transplant Recipients (2003-2015) to identify patients who underwent urgent LT for acute hepatic necrosis (AHN) and identified those with HDS use. This group of patients was then characterized...
March 2017: Transplantation Proceedings
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