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Acetaminophen toxicity

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https://www.readbyqxmd.com/read/29328974/novel-approach-for-evaluating-pharmaceuticals-toxicity-using-daphnia-model-analysis-of-the-mode-of-cytochrome-p450-generated-metabolite-action-after-acetaminophen-exposure
#1
Ryeo-Ok Kim, Min-A Jo, Jinhaeng Song, Il-Chan Kim, Seokjoo Yoon, Woo-Keun Kim
Because of its widespread use, the pharmaceutical acetaminophen (APAP) is frequently detected in aquatic environments. APAP can have serious physiological effects, such as reduced reproduction, low growth rates, and abnormal behavior, in aquatic organisms. However, the methods available for evaluation of the aquatic toxicity of APAP are of limited usefulness. The present study aimed to develop reliable and sensitive markers for evaluation of APAP toxicity using Daphnia as a model organism. We focused on N-acetyl-p-benzoquinoneimine (NAPQI) production from APAP via cytochrome P450 metabolism because NAPQI causes APAP toxicity...
December 30, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/29301418/hypoglycemia-and-lactic-acidosis-outperform-king-s-college-criteria-for-predicting-death-or-transplant-in-acetaminophen-toxic-patients
#2
Michael Levine, Samuel J Stellpflug, Anthony F Pizon, David A Peak, Janna Villano, Timothy Wiegand, Christian Dib, Stephen H Thomas
IMPORTANCE: Acetaminophen toxicity is common and is characterized by hepatic failure. In cases that are not improving with standard medical therapy with N-acetylcysteine, some patients may require hepatic transplant. While there are various criteria to predict patients who might benefit from transplant, the King's College criteria remain one of the most widely used. However, the King's College criteria have several limitations and do not incorporate glucose, an important marker of hepatic function...
January 5, 2018: Clinical Toxicology
https://www.readbyqxmd.com/read/29258884/drug-toxicity-profiling-of-a-saccharomyces-cerevisiae-deubiquitinase-deletion-panel-shows-that-acetaminophen-mimics-tyrosine
#3
Angelina Huseinovic, Marc van Dijk, Nico P E Vermeulen, Fred van Leeuwen, Jan M Kooter, J Chris Vos
Post-translational protein modification by addition or removal of the small polypeptide ubiquitin is involved in a range of critical cellular processes, like proteasomal protein degradation, DNA repair, gene expression, internalization of membrane proteins, and drug sensitivity. We recently identified genes important for acetaminophen (APAP) toxicity in a comprehensive screen and our findings suggested that a small set of yeast strains carrying deletions of ubiquitin-related genes can be informative for drug toxicity profiling...
December 16, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29233977/the-mitochondrial-negative-regulator-mcj-is-a-therapeutic-target-for-acetaminophen-induced-liver-injury
#4
Lucía Barbier-Torres, Paula Iruzubieta, David Fernández-Ramos, Teresa C Delgado, Daniel Taibo, Virginia Guitiérrez-de-Juan, Marta Varela-Rey, Mikel Azkargorta, Nicolas Navasa, Pablo Fernández-Tussy, Imanol Zubiete-Franco, Jorge Simon, Fernando Lopitz-Otsoa, Sofia Lachiondo-Ortega, Javier Crespo, Steven Masson, Misti Vanette McCain, Erica Villa, Helen Reeves, Felix Elortza, Maria Isabel Lucena, Maria Isabel Hernández-Alvarez, Antonio Zorzano, Raúl J Andrade, Shelly C Lu, José M Mato, Juan Anguita, Mercedes Rincón, María Luz Martínez-Chantar
Acetaminophen (APAP) is the active component of many medications used to treat pain and fever worldwide. Its overuse provokes liver injury and it is the second most common cause of liver failure. Mitochondrial dysfunction contributes to APAP-induced liver injury but the mechanism by which APAP causes hepatocyte toxicity is not completely understood. Therefore, we lack efficient therapeutic strategies to treat this pathology. Here we show that APAP interferes with the formation of mitochondrial respiratory supercomplexes via the mitochondrial negative regulator MCJ, and leads to decreased production of ATP and increased generation of ROS...
December 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/29212634/intravenous-n-acetylcysteine-for-acetaminophen-toxicity
#5
Alyssa N Fixl, Robert M Woods, Katelyn Dervay
No abstract text is available yet for this article.
2017: AACN Advanced Critical Care
https://www.readbyqxmd.com/read/29189681/placental-abruption-with-delayed-fetal-compromise-in-maternal-acetaminophen-toxicity
#6
Corinne McLeod, Renee Samelson
No abstract text is available yet for this article.
December 2017: Obstetrics and Gynecology
https://www.readbyqxmd.com/read/29188694/supra-therapeutic-oral-paracetamol-overdose-in-adults-an-update-for-the-dental-team
#7
Ross Leader, James Hackett, Ahmed Al-Naher
Paracetamol (acetaminophen) is a commonly used analgesic; its 'over the counter' availability, low cost and popularity amongst patients often make it the first choice for dental pain. It is in this that its potential toxicity, made more complicated by the ever extending range of paracetamol-containing products, make the understanding of this medication key to the safe management of patients presenting to surgery with dental pain. Clinical relevance: The purpose of this article is to supply dental practitioners with the knowledge to manage patients who present having taken an oral supra-therapeutic paracetamol overdose...
May 2017: Dental Update
https://www.readbyqxmd.com/read/29184146/2-3-4-5-tetrahydroxystilbene-2-o-%C3%AE-d-glucoside-exacerbates-acetaminophen-induced-hepatotoxicity-by-inducing-hepatic-expression-of-cyp2e1-cyp3a4-and-cyp1a2
#8
Shangfu Xu, Jie Liu, Jingshan Shi, Zhengtao Wang, Lili Ji
Hepatotoxicity induced by medicinal herb Polygonum multiflorum Thunb. attracts wide attention in the world recently. 2,3,4',5-tetrahydroxystilbene-2-O-β-D-glucoside (TSG) is a main active compound in Polygonum multiflorum Thunb. This study aims to observe TSG-provided the aggravation on acetaminophen (APAP)-induced hepatotoxicity in mice by inducing hepatic expression of cytochrome P450 (CYP450) enzymes. Serum alanine/aspartate aminotransferase (ALT/AST) analysis and liver histological evaluation showed that TSG (200, 400, 800 mg/kg) exacerbated the hepatotoxicity induced by sub-toxic dose of APAP (200 mg/kg) in mice, but TSG alone had no hepatotoxicity...
November 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29173208/dietary-supplementation-with-cysteine-prevents-adverse-metabolic-outcomes-of-repeated-cures-with-paracetamol-in-old-rats
#9
Carole Mast, Charlène Pourpe, Guillaume Voyard, Didier Rémond, Carole Migné, Delphine Centeno, Dominique Dardevet, Isabelle Savary-Auzeloux, Isabelle Papet
Cysteine (Cys), a conditionally indispensable amino acid, is required for the detoxification of paracetamol (acetaminophen, N-acetyl-para-aminophenol, 4-hydroxy-acetanilide, APAP), a drug of widespread use in older persons. We recently reported that repeated APAP cures could worsen sarcopenia in old rats, likely to be due to the impairment of Cys/GSH homoeostasis. The aim of the study was to evaluate whether a dietary Cys supplementation during APAP cures could improve Cys/GSH homoeostasis and thus preserve skeletal muscle...
December 2017: British Journal of Nutrition
https://www.readbyqxmd.com/read/29167567/real-time-in-vivo-imaging-reveals-localised-nrf2-stress-responses-associated-with-direct-and-metabolism-dependent-drug-toxicity
#10
Shiva S Forootan, Fiona E Mutter, Anja Kipar, Takao Iwawaki, Ben Francis, Christopher E Goldring, B Kevin Park, Ian M Copple
The transcription factor Nrf2 coordinates an adaptive response to chemical and oxidative stress characterised by the upregulated expression of cytoprotective target genes. In order to understand the mechanistic relevance of Nrf2 as a marker of drug-induced stress it is important to know if this adaptive response is truly localised in the context of organ-specific drug toxicity. Here, we address this knowledge gap through real-time bioluminescence imaging of transgenic Nrf2-luciferase (Nrf2-luc) reporter mice following administration of the metabolism-dependent hepatotoxin acetaminophen (APAP) or the direct nephrotoxin cisplatin...
November 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29158815/tethering-interleukin-22-to-apolipoprotein-a-i-ameliorates-mice-from-acetaminophen-induced-liver-injury
#11
Wei Chen, Xuyao Zhang, Jiajun Fan, Wenjing Zai, Jingyun Luan, Yubin Li, Shaofei Wang, Qicheng Chen, Yichen Wang, Yanxu Liang, Dianwen Ju
Increasing evidence indicates that interleukin-22 (IL-22) holds tremendous potential as a protective agent in preventing liver injury, but its pleiotropic effects and pathogenic role in carcinogenesis, rheumatoid arthritis and psoriasis restrict its systemic application. Here, we first developed a nanoparticle (liposIA) as a liver-targeted agent through IL-22 tethered to apolipoprotein A-I (ApoA-I) in a gene therapy vector. LiposIA was prepared using thin film dispersion method and the complexes exhibited desirable nanoparticle size, fine polydisperse index, highly efficient transfection, and excellent serum and storage stability...
2017: Theranostics
https://www.readbyqxmd.com/read/29151582/il-1%C3%AE-in-acetaminophen-toxicity-a-sterile-danger-signal
#12
Arvin Iracheta-Vellve, Gyongyi Szabo
No abstract text is available yet for this article.
November 20, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/29079404/knowledge-of-appropriate-acetaminophen-use-a-survey-of-college-age-women
#13
Janice L Stumpf, Allison C Liao, Stacy Nguyen, Amy J Skyles, Cesar Alaniz
OBJECTIVES: To evaluate college-age women's knowledge of appropriate doses and potential toxicities of acetaminophen, competency in interpreting Drug Facts label dosing information, and ability to recognize products containing acetaminophen. METHODS: In this cross-sectional prospective study, a 20-item written survey was provided to female college students at a University of Michigan fundraising event in March 2015. RESULTS: A total of 203 female college students, 18-24 years of age, participated in the study...
October 24, 2017: Journal of the American Pharmacists Association: JAPhA
https://www.readbyqxmd.com/read/29067470/multiple-micrornas-function-as-self-protective-modules-in-acetaminophen-induced-hepatotoxicity-in-humans
#14
Dianke Yu, Leihong Wu, Pritmohinder Gill, William H Tolleson, Si Chen, Jinchun Sun, Bridgett Knox, Yaqiong Jin, Wenming Xiao, Huixiao Hong, Yong Wang, Zhen Ren, Lei Guo, Nan Mei, Yongli Guo, Xi Yang, Leming Shi, Yinting Chen, Linjuan Zeng, Kostiantyn Dreval, Volodymyr Tryndyak, Igor Pogribny, Hong Fang, Tieliu Shi, Sandra McCullough, Sudeepa Bhattacharyya, Laura Schnackenberg, William Mattes, Richard D Beger, Laura James, Weida Tong, Baitang Ning
Acetaminophen (APAP) overdose is the leading cause of acute liver failure. Yet the mechanisms underlying adaptive tolerance toward APAP-induced liver injury are not fully understood. To better understand molecular mechanisms contributing to adaptive tolerance to APAP is an underpinning foundation for APAP-related precision medicine. In the current study, the mRNA and microRNA (miRNA) expression profiles derived from next generation sequencing data for APAP-treated (5 and 10 mM) HepaRG cells and controls were analyzed systematically...
October 24, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/29056914/acetaminophen-induced-liver-injury-alters-the-acyl-ethanolamine-based-anti-inflammatory-signaling-system-in-liver
#15
Patricia Rivera, Antoni Pastor, Sergio Arrabal, Juan Decara, Antonio Vargas, Laura Sánchez-Marín, Francisco J Pavón, Antonia Serrano, Dolores Bautista, Anna Boronat, Rafael de la Torre, Elena Baixeras, M Isabel Lucena, Fernando R de Fonseca, Juan Suárez
Protective mechanisms against drug-induced liver injury are actively being searched to identify new therapeutic targets. Among them, the anti-inflammatory N-acyl ethanolamide (NAE)-peroxisome proliferators activated receptor alpha (PPARα) system has gained much interest after the identification of its protective role in steatohepatitis and liver fibrosis. An overdose of paracetamol (APAP), a commonly used analgesic/antipyretic drug, causes hepatotoxicity, and it is being used as a liver model. In the present study, we have analyzed the impact of APAP on the liver NAE-PPARα system...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29054140/acetaminophen-toxicity-novel-insights-into-mechanisms-and-future-perspectives
#16
Anup Ramachandran, Hartmut Jaeschke
Acetaminophen (APAP) overdose is the most common cause of acute liver failure in the United States and decades of intense study of its pathogenesis resulted in development of the antidote Nacetylcysteine, which facilitates scavenging of the reactive metabolite and is the only treatment in clinical use. However, the narrow therapeutic window of this intervention necessitates a better understanding of the intricacies of APAP-induced liver injury for development of additional therapeutic approaches which can benefit late presenting patients...
October 20, 2017: Gene Expression
https://www.readbyqxmd.com/read/29050482/the-effect-of-sulforaphane-on-oxidative-stress-and-inflammation-in-rats-with-toxic-hepatitis-induced-by-acetaminophene
#17
E Dokumacioglu, H Iskender, M S Aktas, B Hanedan, A Dokumacioglu, T M Sen, A Musmul
OBJECTIVE: The aim of the present study was to reveal the possible effect of sulforaphane on oxidative stress and inflammation in rats liver with toxic hepatitis induced by acetaminophene. BACKGROUND: Sulforaphane is a compound with high antioxidant properties. Acetaminophen, which is a para-aminophenol derivative, can lead to fatal hepatic necrosis with direct hepatotoxic effects at high doses. METHODS: Thirty six male Sprague-Dawley rats were randomly divided into four groups...
2017: Bratislavské Lekárske Listy
https://www.readbyqxmd.com/read/28971616/kinetic-characterizations-of-diallyl-sulfide-analogs-for-their-novel-role-as-cyp2e1-enzyme-inhibitors
#18
Mohammad A Rahman, Narasimha M Midde, Xiaoxin Wu, Wei Li, Santosh Kumar
Diallyl sulfide (DAS), a selective inhibitor of CYP2E1, has shown protective effects against alcohol- and acetaminophen-induced hepatotoxicity in many studies. However, DAS is also a CYP2E1 substrate that on metabolism produces toxic metabolites and causes cytotoxicity. The objective of this study was to find a potent DAS analog as a CYP2E1 inhibitor and has the characteristic of producing less toxic metabolites. We selected seven commercially available compounds that are similar to DAS (DAS analogs). First, we performed ligand-CYP2E1 docking study to determine the binding mode and binding energy...
October 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28967362/pain-management-in-rheumatology-research-training-and-practice
#19
REVIEW
David G Borenstein, Afton L Hassett, David Pisetsky
The Pain Management Task Force of the American College of Rheumatology published a report in 2010 highlighting pain management as a fundamental aspect of clinical practice, training and research. In the interim, the consideration of pain as a focus of attention of rheumatologists and rheumatology health professionals has become even more challenging than in 2010 because of the epidemic of opiate addiction and overdose death. The characterisation of categories of pain by mechanism (e.g., inflammation, joint degeneration, abnormalities of central pain processing) can help guide treatment...
September 2017: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/28965396/caspase-mediated-anti-apoptotic-effect-of-ginsenoside-rg5-a-main-rare-ginsenoside-on-acetaminophen-induced-hepatotoxicity-in-mice
#20
Zi Wang, Jun-Nan Hu, Meng-Han Yan, Jing-Jing Xing, Wen-Cong Liu, Wei Li
Frequent overdose of acetaminophen (APAP) is one of the most common and important incentives of acute hepatotoxicity. Prior to this work, our research group confirmed that black ginseng (Panax ginseng, BG) showed powerful protective effects on APAP-induced ALI. However, it is not clear which kind of individual ginsenoside from BG plays such a liver protection effect. The objective of the current investigation was to evaluate whether ginsenoside Rg5 (G-Rg5) protected against APAP-induced hepatotoxicity and the involved action mechanisms...
October 16, 2017: Journal of Agricultural and Food Chemistry
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