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Acetaminophen toxicity

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https://www.readbyqxmd.com/read/29079404/knowledge-of-appropriate-acetaminophen-use-a-survey-of-college-age-women
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
https://www.readbyqxmd.com/read/28963996/is-acetaminophen-associated-with-a-risk-of-stevens-johnson-syndrome-and-toxic-epidermal-necrolysis-analysis-of-the-french-pharmacovigilance-database
#9
Bénédicte Lebrun-Vignes, Claire Guy, Marie-Josèphe Jean-Pastor, Valérie Gras-Champel, Marie Zenut
AIM: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but severe mostly drug-induced cutaneous reactions. Acetaminophen is an over-the-counter drug used worldwide to treat pain and reduce fever. In 2013, the US Food and Drug Administration informed the public that acetaminophen was associated with a rare risk of SJS/TEN. The aim of the present retrospective study was to analyse reports of acetaminophen as a possible suspect in the development of SJS/TEN from the French Pharmacovigilance Database (FPDB)...
September 30, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28963035/mirna-122-protects-mice-and-human-hepatocytes-from-acetaminophen-toxicity-by-regulating-cytochrome-p450-family-2-subfamily-a-member-2-and-e-member-1-expression
#10
Vivek Chowdhary, Kun-Yu Teng, Sharda Thakral, Bo Zhang, Cho-Hao Lin, Nissar Wani, Lei Bruschweiler-Li, Xiaoli Zhang, Laura James, Dakai Yang, Norman Junge, Rafael Brüschweiler, William M Lee, Kalpana Ghoshal
Acetaminophen toxicity is a leading cause of acute liver failure (ALF). We found that miRNA-122 (miR-122) is down-regulated in liver biopsy specimens of patients with ALF and in acetaminophen-treated mice. A marked decrease in the primary miR-122 expression occurs in mice on acetaminophen overdose because of suppression of its key transactivators, hepatocyte nuclear factor (HNF)-4α and HNF6. More importantly, the mortality rates of male and female liver-specific miR-122 knockout (LKO) mice were significantly higher than control mice when injected i...
September 28, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28962074/study-of-pharmaceuticals-in-surface-and-wastewater-from-cuernavaca-morelos-mexico-occurrence-and-environmental-risk-assessment
#11
José Abraham Rivera-Jaimes, Cristina Postigo, Rosa María Melgoza-Alemán, Jaume Aceña, Damia Barceló, Miren López de Alda
The present work describes the first known study to date on the occurrence of pharmaceuticals in surface water and wastewater of Cuernavaca, the capital of the state of Morelos (México). Selected pharmaceuticals (a total of 35) were extracted from the collected water samples with a generic solid phase extraction (SPE) protocol and determined in the sample extracts by means of high-performance liquid chromatography coupled to electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS). A screening level risk assessment combining the measured environmental concentrations (MECs) with dose-response data based on predicted no-effect concentrations (PNECs) was also applied to estimate Hazard Quotients (HQs) for the pharmaceuticals detected in the investigated area...
February 1, 2018: Science of the Total Environment
https://www.readbyqxmd.com/read/28951593/microrna-regulation-of-cyp-1a2-cyp3a4-and-cyp2e1-expression-in-acetaminophen-toxicity
#12
Pritmohinder Gill, Sudeepa Bhattacharyya, Sandra McCullough, Lynda Letzig, Prasun J Mishra, Chunqiao Luo, Harsh Dweep, Laura James
MicroRNAs (miRNAs) that regulate the cytochrome P-450 isoforms involved in acetaminophen (APAP) toxicity were examined in HepaRG cells treated with APAP (20 mM). In-vitro studies found that APAP protein adducts were increased at 1 h, followed by ALT increases at 12 and 24 h. CYP1A2, CYP3A4 and CYP2E1 mRNA levels were decreased, while miRNAs were increased for miR-122-5p, miR-378a-5p, miR-27b-3p at 6 h and miR-125b-5p at 12 h and miR-27b-3p at 24 h. Putative miRNA binding sites on the 3'UTRs of the CYPs were identified in-silico...
September 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28945963/the-analgesic-acetaminophen-and-the-antipsychotic-clozapine-can-each-redox-cycle-with-melanin
#13
Zülfikar Temoçin, Eunkyoung Kim, Jinyang Li, Lucia Panzella, Maria Laura Alfieri, Alessandra Napolitano, Deanna L Kelly, William E Bentley, Gregory F Payne
Melanins are ubiquitous but their complexity and insolubility has hindered characterization of their structures and functions. We are developing electrochemical reverse engineering methodologies that focus on properties and especially on redox properties. Previous studies have shown that melanins (i) are redox-active and can rapidly and repeatedly exchange electrons with diffusible oxidants and reductants, and (ii) have redox potentials in midregion of the physiological range. These properties suggest the functional activities of melanins will depend on their redox context...
October 9, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28945927/co-ingestion-of-aspirin-and-acetaminophen-promoting-fulminant-liver-failure-a-critical-review-of-reye-syndrome-in-the-current-perspective-at-the-dawn-of-the-21-st-century
#14
REVIEW
Deepak Dinakaran, Consolato Sergi
In the pediatric population, there is some evidence of possible interaction, synergism, and co-toxicity of aspirin and acetaminophen. The toxicity of salicylates such as aspirin in this population is well known and documented, specifically in the form of Reye syndrome. The possible toxic synergism with aspirin and acetaminophen, however, is not previously described; though case reports suggest such co-toxicities with low levels of aspirin and other compounds can exist. In vitro studies into mechanistic processes of salicylate toxicity propose that there are a bi-directional link and potentiation with glutathione (GSH) depletion and salicylate toxicity...
September 25, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28928980/common-yet-elusive-a-case-of-severe-anion-gap-acidosis
#15
Akanksha Agrawal, Marina Kishlyansky, Sylvia Biso, Soumya Patnaik, Chitra Punjabi
Acid-base disturbances are common occurrence in hospitalized patients with life threatening complications. 5-oxoproline has been increasingly recognized as cause of high anion gap metabolic acidosis (AGMA) in association with chronic acetaminophen use. However, laboratory workup for it are not widely available. We report case of 56-year-old female with severe AGMA not attributable to ketoacidosis, lactic acidosis or toxic ingestion. History was significant for chronic acetaminophen use, and laboratory workup negative for all frequent causes of AGMA...
September 2017: Oxford Medical Case Reports
https://www.readbyqxmd.com/read/28924552/schisandra-sphenanthera-extract-wuzhi-tablet-protects-against-chronic-binge-and-acute-alcohol-induced-liver-injury-by-regulating-the-nrf2-are-pathway-in-mice
#16
Xuezhen Zeng, Xi Li, Chenshu Xu, Fulin Jiang, Yufei Mo, Xiaomei Fan, Yaoting Li, Yiming Jiang, Dongshun Li, Min Huang, Huichang Bi
Alcohol abuse leads to alcoholic liver disease and no effective therapy is currently available. Wuzhi Tablet (WZ), a preparation of extract from Schisandra sphenanthera that is a traditional hepato-protective herb, exerted a significant protective effect against acetaminophen-induced liver injury in our recent studies, but whether WZ can alleviate alcohol-induced toxicity remains unclear. This study aimed to investigate the contribution of WZ to alcohol-induced liver injury by using chronic-binge and acute models of alcohol feeding...
September 2017: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/28918124/polyphenols-reported-to-shift-apap-induced-changes-in-mapk-signaling-and-toxicity-outcomes
#17
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...
November 1, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28894628/tigernut-cyperus-esculentus-l-milk-as-a-potent-nutri-drink-for-the-prevention-of-acetaminophen-induced-hepatotoxicity-in-a-murine-model
#18
Nnenna Ola Onuoha, Nneoma Oleh Ogbusua, Augustine N Okorie, Chukwunonso E C C Ejike
AIM/BACKGROUND: Given the prevalence of toxicants in foods, beauty products, etc., and the increasing demand for "green" products, there is a need for the development of "nutri-drinks" with hepatoprotective properties. The usefulness of tigernut milk (TNM) in preventing acetaminophen (APAP)-induced liver injury was, therefore, investigated. MATERIALS AND METHODS: A total of 25 rats were randomized into five equal groups. Four groups were treated with 0, 500, 1000, and 2000 kg/mg body weight (bw) TNM, respectively, per os for 2 weeks before they were challenged with 2500 mg/kg bw APAP...
July 2017: Journal of Intercultural Ethnopharmacology
https://www.readbyqxmd.com/read/28878168/metabolomics-analysis-of-urine-samples-from-children-after-acetaminophen-overdose
#19
Laura K Schnackenberg, Jinchun Sun, Sudeepa Bhattacharyya, Pritmohinder Gill, Laura P James, Richard D Beger
Acetaminophen (APAP), a commonly used over-the-counter analgesic, accounts for approximately fifty percent of the cases of acute liver failure (ALF) in the United States due to overdose, with over half of those unintentional. Current clinical approaches for assessing APAP overdose rely on identifying the precise time of overdose and quantitating acetaminophen alanine aminotransferase (ALT) levels in peripheral blood. Novel specific and sensitive biomarkers may provide additional information regarding patient status post overdose...
September 6, 2017: Metabolites
https://www.readbyqxmd.com/read/28867745/non-toxic-level-of-acetaminophen-potentiates-carbon-tetrachloride-induced-hepatotoxicity-in-mice
#20
Shiori Fukaya, Hiroki Yoshioka, Tadahiro Okano, Akito Nagatsu, Nobuhiko Miura, Tsunemasa Nonogaki, Satomi Onosaka
A wide range of medications are routinely used to maintain and improve human health. Hence, it is essential that we understand and predict adverse effects caused by the combined use of multiple medications. In the present study, we investigated whether the combination of carbon tetrachloride (CCl4) and acetaminophen (APAP) had a detrimental effect on the liver. Mice injected with APAP (100 mg/kg) showed no significant changes in hepatic injury markers (alanine aminotransferase and aspartate aminotransferase), histopathological findings, pro-inflammatory cytokine levels, or hepatic oxidative stress...
2017: Biological & Pharmaceutical Bulletin
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