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Acetaminophen toxicity

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https://www.readbyqxmd.com/read/28720398/perinatal-and-neonatal-use-of-paracetamol-for-pain-relief
#1
REVIEW
Karel Allegaert, John N van den Anker
Paracetamol (acetaminophen) is the most widely used drug to treat pain or fever in pregnant women or neonates, but its pharmacokinetics (PK) and pharmacodynamics (PD) warrant a focused analysis. During pregnancy, there is an important increase in paracetamol clearance. Consequently, it is reasonable to anticipate that the analgesic effect of paracetamol will decrease faster, whereas higher doses may result in even higher oxidative toxic metabolites. Therefore, most peripartal PD data relate to multimodal analgesia strategies...
July 15, 2017: Seminars in Fetal & Neonatal Medicine
https://www.readbyqxmd.com/read/28717379/hepatoprotective-effect-of-citral-on-acetaminophen-induced-liver-toxicity-in-mice
#2
Nancy Sayuri Uchida, Saulo Euclides Silva-Filho, Gabriel Fernando Esteves Cardia, Edivaldo Cremer, Francielli Maria de Souza Silva-Comar, Expedito Leite Silva, Ciomar Aparecida Bersani-Amado, Roberto Kenji Nakamura Cuman
High doses of acetaminophen (APAP) lead to acute liver damage. In this study, we evaluated the effects of citral in a murine model of hepatotoxicity induced by APAP. The liver function markers alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and gamma-glutamyl transferase (γGT) were determined to evaluate the hepatoprotective effects of citral. The livers were used to determine myeloperoxidase (MPO) activity and nitric oxide (NO) production and in histological analysis...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28699415/a-scalable-approach-for-the-generation-of-human-pluripotent-stem-cell-derived-hepatic-organoids-with-sensitive-hepatotoxicity-features
#3
Malte Sgodda, Zhen Dai, Robert Zweigerdt, Amar D Sharma, Michael Ott, Tobias Cantz
The quest for physiologically-active human hepatocyte-like cells for in vitro research and drug screening is high. The recent progress in the field of pluripotent stem cell (PSC) - derived hepatic cells within the last decade brings those cells closer to applications in translational medicine. However, the classical two-dimensional (2D) cell culture systems are of limited use, because relevant cell-cell interactions based on cell polarity, which is a major prerequisite for proper hepatic cell metabolisms, are not provided...
July 12, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28690122/hepatoprotective-effects-of-ethanol-extracts-from-folium-syringae-against-acetaminophen-induced-hepatotoxicity-in%C3%A2-vitro-and-in%C3%A2-vivo
#4
Chen-Xi Shi, Yue-Xia Lin, Fang-Ping Liu, Yi-Cong Chang, Rui Li, Chang-Wen Li, Ying Li, Jing-Shan He, Xin Ma, Zhi Li
BACKGROUND: The leaves of Folium Syringae (FS) have been long used as a traditional Chinese folk medicine for their anti-inflammatory effect, utilized as an antibacterial and antiviral treatment. The purpose of this study was to investigate the potential hepatoprotective effects of FS on acetaminophen-induced hepatic injury in primary hepatocytes and mice. METHODS: Hepatocytes obtained by the inverse perfusion method were divided randomly into five groups. Prior to acetaminophen exposure, 3 different doses of FS ethanol extracts were given to hepatocytes and mice, respectively...
July 6, 2017: Journal of the Chinese Medical Association: JCMA
https://www.readbyqxmd.com/read/28680622/a-case-of-reversible-drug-induced-liver-failure
#5
Mohammad Ansari, Sabrina Arshed, Mohammed Islam, Shuvendu Sen, Abdalla Yousif
Acute fulminant liver failure and acute renal failure are devastating complications caused by many drugs. The use of N-acetylcysteine has been well established in acetaminophen toxicity, but it remains controversial in other cases. Dialysis is a very effective method of removing certain drugs from the system. With the invention of new street drugs such as "synthetic marijuana," it may be beneficial in patients whom the substances ingested are unknown. We report a case of a 42-year-old male who developed acute fulminant hepatic failure and acute renal failure, who was cured with dialysis, N-acetylcysteine, and other supportive measures...
July 2017: Clinical Case Reports
https://www.readbyqxmd.com/read/28678845/polymerase-free-measurement-of-microrna-122-with-single-base-specificity-using-single-molecule-arrays-detection-of-drug-induced-liver-injury
#6
David M Rissin, Barbara López-Longarela, Salvatore Pernagallo, Hugh Ilyine, A D Bastiaan Vliegenthart, James W Dear, Juan J Díaz-Mochón, David C Duffy
We have developed a single probe method for detecting microRNA from human serum using single molecule arrays, with sequence specificity down to a single base, and without the use of amplification by polymerases. An abasic peptide nucleic acid (PNA) probe-containing a reactive amine instead of a nucleotide at a specific position in the sequence-for detecting a microRNA was conjugated to superparamagnetic beads. These beads were incubated with a sample containing microRNA, a biotinylated reactive nucleobase-containing an aldehyde group-that was complementary to the missing base in the probe sequence, and a reducing agent...
2017: PloS One
https://www.readbyqxmd.com/read/28661486/the-role-of-map2-kinases-and-p38-kinase-in-acute-murine-liver-injury-models
#7
Jun Zhang, Robert W M Min, Khanh Le, Sheng Zhou, Mariam Aghajan, Tin A Than, Sanda Win, Neil Kaplowitz
c-Jun N-terminal kinase (JNK) mediates hepatotoxicity through interaction of its phospho-activated form with a mitochondrial outer membrane protein, Sh3bp5 or Sab, leading to dephosphorylation of intermembrane Src and consequent impaired mitochondrial respiration and enhanced ROS release. ROS production from mitochondria activates MAP3 kinases, such as MLK3 and ASK1, which continue to activate a pathway to sustain JNK activation, and amplifies the toxic effect of acetaminophen (APAP) and TNF/galactosamine (TNF/GalN)...
June 29, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28636309/quantitative-chemical-proteomic-profiling-of-the-in-vivo-targets-of-reactive-drug-metabolites
#8
Landon R Whitby, R Scott Obach, Gabriel M Simon, Matthew M Hayward, Benjamin F Cravatt
Idiosyncratic liver toxicity represents an important problem in drug research and pharmacotherapy. Reactive drug metabolites that modify proteins are thought to be a principal factor in drug-induced liver injury. Here, we describe a quantitative chemical proteomic method to identify the targets of reactive drug metabolites in vivo. Treating mice with clickable analogues of four representative hepatotoxic drugs, we demonstrate extensive covalent binding that is confined primarily to the liver. Each drug exhibited a distinct target profile that, in certain cases, showed strong enrichment for specific metabolic pathways (e...
June 21, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28599208/occurrence-of-pharmaceutical-recreational-and-psychotropic-drug-residues-in-surface-water-on-the-northern-antarctic-peninsula-region
#9
Silvia González-Alonso, Luis Moreno Merino, Sara Esteban, Miren López de Alda, Damià Barceló, Juan José Durán, Jerónimo López-Martínez, Jaume Aceña, Sandra Pérez, Nicola Mastroianni, Adrián Silva, Myriam Catalá, Yolanda Valcárcel
Human presence in the Antarctic is increasing due to research activities and the rise in tourism. These activities contribute a number of potentially hazardous substances. The aim of this study is to conduct the first characterisation of the pharmaceuticals and recreational drugs present in the northern Antarctic Peninsula region, and to assess the potential environmental risk they pose to the environment. The study consisted of a single sampling of ten water samples from different sources, including streams, ponds, glacier drains, and a wastewater discharge into the sea...
June 6, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28594770/placental-abruption-with-delayed-fetal-compromise-in-maternal-acetaminophen-toxicity
#10
Juliana Taney, Hannah Anastasio, Amanda Paternostro, Vincenzo Berghella, Amanda Roman
BACKGROUND: After maternal acetaminophen overdose, fetal fulminant liver failure, stillbirth, neonatal death, or preterm delivery may occur. CASE: A 27-year-old woman, gravida 2 para 1, presented at 28 weeks of gestation after unintentional acetaminophen overdose. Four days after ingestion, her laboratory values worsened, including serum aspartate aminotransferase of 5,460 units/L, alanine aminotransferase of 4,936 units/L, and international normalized ratio of 2...
June 6, 2017: Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28586753/ozonation-as-a-pretreatment-process-for-nanofiltration-brines-monitoring-of-transformation-products-and-toxicity-evaluation
#11
Antonin Azaïs, Julie Mendret, Guillaume Cazals, Eddy Petit, Stephan Brosillon
Considerable interest has been given to using nanofiltration (NF) in lieu of reverse osmosis for water reclamation schemes due to lower energy consumption, higher flux rates while ensuring good micropollutants rejection. The application NF results in the generation of a large concentrated waste stream. Treatment of the concentrate is a major hurdle for the implementation of membrane technologies since the concentrate is usually unusable due to a large pollutants content. This work focuses on the application of ozonation as pretreatment of urban NF concentrates, the generation of transformation products and their relative toxicity...
May 30, 2017: Journal of Hazardous Materials
https://www.readbyqxmd.com/read/28583670/hepatic-hypoxia-inducible-factors-inhibit-ppar%C3%AE-expression-to-exacerbate-acetaminophen-induced-oxidative-stress-and-hepatotoxicity
#12
Dawei Li, Yingdong Du, Xiaodong Yuan, Xiaoxiao Han, Zhen Dong, Xiaosong Chen, Haoyu Wu, Jianjun Zhang, Longmei Xu, Conghui Han, Ming Zhang, Qiang Xia
Oxidative stress has a critical role in the pathogenesis of acetaminophen (APAP) induced hepatocellular necrosis, and the identification of novel approaches to attenuate oxidative stress is essential to prevent/revert the disease. This study investigated the role of both HIF-1 and HIF-2 in the pathogenesis of APAP-induced oxidative stress, as well as the underlying mechanisms. In the present study, we initially found that knockout of HIF-1α or HIF-2α reduced APAP toxicity, and double knockout afforded the best protection...
June 3, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28580117/two-photon-fluorescent-probe-for-revealing-drug-induced-hepatotoxicity-via-mapping-fluctuation-of-peroxynitrite
#13
Yong Li, Xilei Xie, Xiu'e Yang, Mengmeng Li, Xiaoyun Jiao, Yuhui Sun, Xu Wang, Bo Tang
Drug-induced injury has attracted increasing attention in public health issues. Among them, hepatotoxicity has been regarded as the leading clinical problem caused by drug toxicity. However, owing to the complexity of the involved pathophysiological mechanisms and the lack of noninvasive, straightforward, and real-time tools, drug-induced hepatotoxicity has rarely been predicted satisfactorily. In this paper, by utilizing the reactive species peroxynitrite (ONOO(-)) as a biomarker, we present a two-photon fluorescent probe, TP-KA, holding rapid response, high specificity and sensitivity towards ONOO(-), to investigate drug (acetaminophen and tolcapone)-related liver injury and the remediate effect of N-acetyl cysteine (NAC)...
May 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/28573237/protective-effect-of-moringa-peregrina-leaves-extract-on-acetaminophen-induced-liver-toxicity-in-albino-rats
#14
Samy Abdelfatah Abdel Azim, Mohamed Taha Abdelrahem, Mostafa Mohamed Said, Alshaimaa Khattab
BACKGROUND: Acetaminophen is a common antipyretic drug but at overdose can cause severe hepatotoxicity that may further develop into liver failure and hepatic centrilobular necrosis in experimental animals and humans. This study was undertaken to assess the ameliorative role of Moringa peregrina leaves extract against acetaminophen toxicity in rats. MATERIALS AND METHODS: Induction of hepatotoxicity was done by chronic oral administration of acetaminophen (750 mg/kg bwt) for 4 weeks...
2017: African Journal of Traditional, Complementary, and Alternative Medicines: AJTCAM
https://www.readbyqxmd.com/read/28571516/nsaids-as-potential-treatment-option-for-preventing-amyloid-%C3%AE-toxicity-in-alzheimer-s-disease-an-investigation-by-docking-molecular-dynamics-and-dft-studies
#15
Faizul Azam, Nada Hussin Alabdullah, Hadeel Mohammed Ehmedat, Abdullah Ramadan Abulifa, Ismail Taban, Sreedevi Upadhyayula
Aggregation of amyloid beta (Aβ) protein considered as one of contributors in development of Alzheimer's disease (AD). Several investigations have identified the importance of non-steroidal anti-inflammatory drugs (NSAIDs) as Aβ aggregation inhibitors. Here, we have examined the binding interactions of 24 NSAIDs belonging to eight different classes, with Aβ fibrils by exploiting docking and molecular dynamics studies. Minimum energy conformation of the docked NSAIDs were further optimized by density functional theory (DFT) employing Becke's three-parameter hybrid model, Lee-Yang-Parr (B3LYP) correlation functional method...
June 15, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28545106/serum-microrna-signatures-as-liquid-biopsies-for-interrogating-hepatotoxic-mechanisms-and-liver-pathogenesis-in-human
#16
Julian Krauskopf, Theo M de Kok, Shelli J Schomaker, Mark Gosink, Deborah A Burt, Patricia Chandler, Roscoe L Warner, Kent J Johnson, Florian Caiment, Jos C Kleinjans, Jiri Aubrecht
MicroRNAs (miRNAs) released into the peripheral circulation upon cellular injury have shown a promise as a new class of tissue-specific biomarkers. We were first to demonstrate that next-generation sequencing analysis of serum from human subjects with acetaminophen-induced liver injury revealed a specific signature of circulating miRNAs. We consequently hypothesized that different types of hepatic liver impairments might feature distinct signatures of circulating miRNAs and that this approach might be useful as minimally invasive diagnostic "liquid biopsies" enabling the interrogation of underlying molecular mechanisms of injury in distant tissues...
2017: PloS One
https://www.readbyqxmd.com/read/28521788/methanol-extract-of-dicranopteris-linearis-l-leaves-impedes-acetaminophen-induced-liver-intoxication-partly-by-enhancing-the-endogenous-antioxidant-system
#17
Zainul Amiruddin Zakaria, Farah Hidayah Kamisan, Maizatul Hasyima Omar, Nur Diyana Mahmood, Fezah Othman, Siti Selina Abdul Hamid, Muhammad Nazrul Hakim Abdullah
BACKGROUND: The present study investigated the potential of methanolic extract of Dicranopteris linearis (MEDL) leaves to attenuate liver intoxication induced by acetaminophen (APAP) in rats. METHODS: A group of mice (n = 5) treated orally with a single dose (5000 mg/kg) of MEDL was first subjected to the acute toxicity study using the OECD 420 model. In the hepatoprotective study, six groups of rats (n = 6) were used and each received as follows: Group 1 (normal control; pretreated with 10% DMSO (extract's vehicle) followed by treatment with 10% DMSO (hepatotoxin's vehicle) (10% DMSO +10% DMSO)), Group 2 (hepatotoxic control; 10% DMSO +3 g/kg APAP (hepatotoxin)), Group 3 (positive control; 200 mg/kg silymarin +3 g/kg APAP), Group 4 (50 mg/kg MEDL +3 g/kg APAP), Group 5 (250 mg/kg MEDL +3 g/kg APAP) or Group 6 (500 mg/kg MEDL +3 g/kg APAP)...
May 18, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28504347/a-rapid-method-to-screen-poisoning-causative-agents-in-an-acute-care-hospital-in-japan
#18
K Usui, H Mori, T Tachi, T Matsumura, K Mori, A Takeda, Y Noguchi, T Yoshimura, H Teramachi
WHAT IS KNOWN AND OBJECTIVE: A simple, rapid analysis is required to simultaneously analyse medicinal toxicants in emergency medical care. In this regard, the analysis of blood samples by LC-MS/MS equipped with a spin column, involving a rapid, simple pretreatment, has attracted attention. In this study, sample pretreatment using a Monospin C18 column was performed to screen 11 medicinal toxicants in blood samples by LC-MS/MS. METHODS: Serum samples supplemented with 11 medical toxicants-acetaminophen, salicylic acid, nitrazepam, diphenhydramine, bromvalerylurea, phenobarbital, amitriptyline, risperidone, fenitrothion, malathion and methomyl-were pretreated with the Monospin C18 column according to Pretreatment I and Pretreatment II, followed by LC-MS/MS analysis...
August 2017: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/28503408/trifluoperazine-inhibits-acetaminophen-induced-hepatotoxicity-and-hepatic-reactive-nitrogen-formation-in-mice-and-in-freshly-isolated-hepatocytes
#19
Sudip Banerjee, Stepan B Melnyk, Kimberly J Krager, Nukhet Aykin-Burns, Sandra S McCullough, Laura P James, Jack A Hinson
The hepatotoxicity of acetaminophen (APAP) occurs by initial metabolism to N-acetyl-p-benzoquinone imine which depletes GSH and forms APAP-protein adducts. Subsequently, the reactive nitrogen species peroxynitrite is formed from nitric oxide (NO) and superoxide leading to 3-nitrotyrosine in proteins. Toxicity occurs with inhibited mitochondrial function. We previously reported that in hepatocytes the nNOS (NOS1) inhibitor NANT inhibited APAP toxicity, reactive nitrogen and oxygen species formation, and mitochondrial dysfunction...
2017: Toxicology Reports
https://www.readbyqxmd.com/read/28501198/introducing-plasma-serum-glycodepletion-for-the-targeted-proteomics-analysis-of-cytolysis-biomarkers
#20
Pauline Maes, Sandrine Donadio-Andréi, Mathilde Louwagie, Yohann Couté, Guillaume Picard, Claire Lacoste, Christophe Bruley, Jérôme Garin, Philippe Ichai, Jamila Faivre, Michel Jaquinod, Virginie Brun
A major class of clinical biomarkers is constituted of intracellular proteins which are leaking into the blood following ischemia, exposure to toxic xenobiotics or mechanical aggression. Their ectopic presence in plasma/serum is an indicator of tissue damage and raises a warning signal. These proteins, referred to as cytolysis biomarkers, are generally of cytoplasmic origin and as such, are devoid of glycosylation. In contrast, most plasma/serum proteins originate from the hepatic secretory pathway and are heavily glycosylated (at the exception of albumin)...
August 1, 2017: Talanta
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