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Acetaminophen toxicity

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https://www.readbyqxmd.com/read/28545106/serum-microrna-signatures-as-liquid-biopsies-for-interrogating-hepatotoxic-mechanisms-and-liver-pathogenesis-in-human
#1
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
#2
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
#3
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...
May 15, 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
#4
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
#5
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
https://www.readbyqxmd.com/read/28489461/estimating-the-impact-of-adopting-the-revised-united-kingdom-acetaminophen-treatment-nomogram-in-the-u-s-population
#6
Michael Levine, Sam Stellpflug, Anthony F Pizon, Stephen Traub, Rais Vohra, Timothy Wiegand, Nicole Traub, David Tashman, Shoma Desai, Jamie Chang, Dhruv Nathwani, Stephen Thomas
BACKGROUND: Acetaminophen toxicity is common in clinical practice. In recent years, several European countries have lowered the treatment threshold, which has resulted in increased number of patients being treated at a questionable clinical benefit. OBJECTIVE: The primary objective of this study is to estimate the cost and associated burden to the United States (U.S.) healthcare system, if such a change were adopted in the U.S. METHODS: This study is a retrospective review of all patients age 14 years or older who were admitted to one of eight different hospitals located throughout the U...
July 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28486401/drug-induced-liver-injury-cascade-of-events-leading-to-cell-death-apoptosis-or-necrosis
#7
REVIEW
Andrea Iorga, Lily Dara, Neil Kaplowitz
Drug-induced liver injury (DILI) can broadly be divided into predictable and dose dependent such as acetaminophen (APAP) and unpredictable or idiosyncratic DILI (IDILI). Liver injury from drug hepatotoxicity (whether idiosyncratic or predictable) results in hepatocyte cell death and inflammation. The cascade of events leading to DILI and the cell death subroutine (apoptosis or necrosis) of the cell depend largely on the culprit drug. Direct toxins to hepatocytes likely induce oxidative organelle stress (such as endoplasmic reticulum (ER) and mitochondrial stress) leading to necrosis or apoptosis, while cell death in idiosyncratic DILI (IDILI) is usually the result of engagement of the innate and adaptive immune system (likely apoptotic), involving death receptors (DR)...
May 9, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28486212/anti-oxidative-and-anti-inflammatory-benefits-of-the-ribonucleoside-analogue-5-azacitidine-in-mice-with-acetaminophen-induced-toxic-hepatitis
#8
Changming Yang, Jun Yi, Xianqiong Gong, Pu Ge, Jie Dai, Ling Lin, Yu Xing, Li Zhang
Toxic hepatitis induced by overdose of acetaminophen (APAP) is one of the major life-threatening problems, oxidative stress and inflammatory injury are the essential underlying mechanisms. 5-Azacytidine (5-AZA) is a ribonucleoside analogue which has been approved for the treatment of patients with acute myeloid leukemia and myelodyplastic syndrome, but recent studies also found that 5-AZA might have anti-oxidative and anti-inflammatory benefits in non-tumor disorders. In the present study, the potential effects of 5-AZA on APAP-induced toxic hepatitis were investigated in a mouse model in vivo...
May 6, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28481086/nontargeted-identification-of-reactive-metabolite-protein-adducts
#9
Michael G Leeming, William A Donald, Richard A J O'Hair
Metabolic bioactivation of many different chemicals results in the formation of highly reactive compounds (chemically reactive metabolites, CRMs) that can lead to toxicity via binding to macromolecular targets (e.g., proteins or DNA). There is a need to develop robust, rapid, and nontargeted analytical techniques to determine the identity of the protein targets of CRMs and their sites of modification. Here, we introduce a nontargeted methodology capable of determining both the identity of a CRM formed from an administered compound as well as the protein targets modified by the reactive metabolite in a single experiment without prior information...
May 16, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28476500/maintenance-of-high-quality-rat-precision-cut-liver-slices-during-culture-to-study-hepatotoxic-responses-acetaminophen-as-a-model-compound
#10
Anne Granitzny, Jan Knebel, Dirk Schaudien, Armin Braun, Pablo Steinberg, Clemens Dasenbrock, Tanja Hansen
Precision cut liver slices (PCLiS) represent a promising tool in reflecting hepatotoxic responses. However, the culture of PCLiS varies considerably between laboratories, which can affect the performance of the liver slices and thus the experimental outcome. In this study, we describe an easily accessible culture method, which ensures optimal slice viability and functionality, in order to set the basis for reproducible and comparable PCLiS studies. The quality of the incubated rat PCLiS was assessed during a 24h culture period using ten readouts, which covered viability (lactate dehydrogenase-, aspartate transaminase- and glutamate dehydrogenase-leakage, ATP content) and functionality parameters (urea, albumin production) as well as histomorphology and other descriptive characteristics (protein content, wet weight, slice thickness)...
May 2, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28475314/exploring-chemical-routes-relevant-to-the-toxicity-of-paracetamol-and-its-meta-analog-at-a-molecular-level
#11
Romina Castañeda-Arriaga, Annia Galano
Several chemical routes related to the toxicity of paracetamol (APAP, also known as acetaminophen), its analog N-acetyl-m-aminophenol (AMAP), and their deacetylated derivatives, were investigated using the Density Functional Theory. It was found that AMAP is more resilient to chemical oxidation than APAP. The chemical degradation of AMAP into radical intermediates is predicted to be significant only when it is induced by strong oxidants. This might explain the apparent contradictions among experimental evidences regarding the AMAP toxicity...
May 5, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28464519/the-haptoglobin-beta-subunit-sequesters-hmgb1-toxicity-in-sterile-and-infectious-inflammation
#12
Huan Yang, Haichao Wang, Yongjun Wang, Meghan Addorisio, Jianhua Li, Michael J Postiglione, Sangeeta S Chavan, Yousef Al-Abed, Daniel J Antoine, Ulf Andersson, Kevin J Tracey
BACKGROUND: Extra-corpuscular hemoglobin is an endogenous factor enhancing inflammatory tissue damage, a process counteracted by the hemoglobin-binding plasma protein haptoglobin composed of alpha and beta subunits connected by disulfide bridges. Recent studies established that haptoglobin also binds and sequesters another pro-inflammatory mediator, HMGB1, via triggering CD163 receptor-mediated anti-inflammatory responses involving heme oxygenase-1 expression and IL-10 release. The molecular mechanism underlying haptoglobin-HMGB1 interaction remains poorly elucidated...
May 2, 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/28462386/association-of-variants-of-arginine-vasopressin-and-arginine%C3%A2-vasopressin-receptor-1a-with-severe-acetaminophen%C3%A2-liver-injury
#13
Matthew Randesi, Orna Levran, Joel Correa da Rosa, Julia Hankins, Jody Rule, Mary Jeanne Kreek, William M Lee
BACKGROUND & AIMS: Acetaminophen-related acute liver injury and liver failure (ALF) result from ingestion of supratherapeutic quantities of this analgesic, frequently in association with other forms of substance abuse including alcohol, opioids, and cocaine. Thus, overdosing represents a unique high-risk behavior associated with other forms of drug use disorder. METHODS: We examined a series of 21 single nucleotide polymorphisms (SNPs) in 9 genes related to impulsivity and/or stress responsivity that may modify response to stress...
May 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28447858/risk-prediction-of-hepatotoxicity-in-paracetamol-poisoning
#14
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
#15
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...
May 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
#16
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 23, 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
#17
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
#18
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
#19
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
#20
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
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