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Acetaminophen toxicity

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https://www.readbyqxmd.com/read/29762685/urine-multi-drug-screening-with-gc-ms-or-lc-ms-ms-using-salle-hybrid-ppt-spe
#1
Junhui Lee, Jiwon Park, Ahra Go, Heesung Moon, Sujin Kim, Sohee Jung, Wonjoon Jeong, Heesun Chung
To intoxicated patients in the emergency room, toxicological analysis can be considerably helpful for identifying the involved toxicants. In order to develop a urine multi-drug screening (UmDS) method, gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-tandem mass spectrometry (LC-MS-MS) were used to determine targeted and unknown toxicants in urine. A GC-MS method in scan mode was validated for selectivity, limit of detection (LOD) and recovery. An LC-MS-MS multiple reaction monitoring (MRM) method was validated for lower LOD, recovery and matrix effect...
May 14, 2018: Journal of Analytical Toxicology
https://www.readbyqxmd.com/read/29751030/high-throughput-toxicity-testing-of-chemicals-and-mixtures-in-organotypic-multi-cellular-cultures-of-primary-human-hepatic-cells
#2
Sophia M Orbach, Marion F Ehrich, Padmavathy Rajagopalan
High-throughput screening (HTS) of liver toxicants can bridge the gap in understanding adverse effects of chemicals on humans. Toxicity testing of mixtures is time consuming and expensive, since the number of possible combinations increases exponentially with the number of chemicals. The combination of organotypic culture models and HTS assays can lead to the rapidly evaluation of chemical toxicity in a cost and time-effective manner while prioritizing chemicals that warrant additional investigation. We describe the design, assembly and toxicant response of multi-cellular hepatic organotypic culture models comprised of primary human or rat cells assembled in 96-well plates (denoted as μOCMs)...
May 8, 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29735980/metabolic-modulation-of-acetaminophen-induced-hepatotoxicity-by-osteopontin
#3
Yankai Wen, Chenchen Wang, Jinyang Gu, Chang Yu, Kaixia Wang, Xuehua Sun, Yun Sun, Hailong Wu, Ying Tong, Qiang Xia, Xiaoni Kong
Induction of osteopontin (OPN), a well-known pro-inflammatory molecule, has been observed in acetaminophen (APAP)-induced hepatotoxicity. However, the precise cell source for OPN induction and its role during APAP-induced hepatotoxicity has not been fully explored. By employing a hepatotoxic mouse model induced by APAP overdose, we demonstrate that both serum and hepatic OPN levels were significantly elevated in response to APAP treatment. Our in vivo and in vitro studies clearly indicated that the induced expression of hepatic OPN was mainly located in necrosis areas and produced by dying or dead hepatocytes...
May 7, 2018: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/29705271/effects-of-human-sult1a3-sult1a4-genetic-polymorphisms-on-the-sulfation-of-acetaminophen-and-opioid-drugs-by-the-cytosolic-sulfotransferase-sult1a3
#4
Ahsan F Bairam, Mohammed I Rasool, Fatemah A Alherz, Maryam S Abunnaja, Amal A El Daibani, Katsuhisa Kurogi, Ming-Cheh Liu
Sulfoconjugation has been shown to be critically involved in the metabolism of acetaminophen (APAP), morphine, tapentadol and O-desmethyl tramadol (O-DMT). The objective of this study was to investigate the effects of single nucleotide polymorphisms (SNPs) of human SULT1A3 and SULT1A4 genes on the sulfating activity of SULT1A3 allozymes toward these analgesic compounds. Twelve non-synonymous coding SNPs (cSNPs) of SULT1A3/SULT1A4 were investigated, and the corresponding cDNAs were generated by site-directed mutagenesis...
April 26, 2018: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29703389/association-of-antioxidant-nutraceuticals-and-acetaminophen-paracetamol-friend-or-foe
#5
REVIEW
Mohamed Abdel-Daim, Abdelrahman Ibrahim Abushouk, Raffaella Reggi, Nagendra Sastry Yarla, Maura Palmery, Ilaria Peluso
Acetaminophen (paracetamol or APAP) is an analgesic and antipyretic drug that can induce oxidative stress-mediated hepatotoxicity at high doses. Several studies reported that antioxidant nutraceuticals, in particular phenolic phytochemicals from dietary food, spices, herbs and algae have hepatoprotective effects. Others, however, suggested that they may negatively impact the metabolism, efficacy and toxicity of APAP. The aim of this review is to discuss the pros and cons of the association of antioxidant nutraceuticals and APAP by reviewing the in vivo evidence, with particular reference to APAP pharmacokinetics and hepatotoxicity...
April 2018: Journal of Food and Drug Analysis
https://www.readbyqxmd.com/read/29694836/in-vitro-evaluation-of-structural-analogs-of-diallyl-sulfide-as-novel-cyp2e1-inhibitors-for-their-protective-effect-against-xenobiotic-induced-toxicity-and-hiv-replication
#6
Mohammad A Rahman, Yuqing Gong, Santosh Kumar
Diallyl sulfide (DAS) has been shown to prevent xenobiotic (e.g. ethanol, acetaminophen) induced toxicity and disease (e.g. HIV-1) pathogenesis. DAS imparts its beneficial effect by inhibiting CYP2E1-mediated metabolism of xenobiotics, especially at high concentration. However, DAS also causes toxicity at relatively high dosages and with long exposure times. Therefore, the goal of the current study was to investigate the structural analogs of DAS for their improved toxicity profiles and their effectiveness in reducing xenobiotic-induced toxicity and HIV-1 replication...
April 22, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29684358/novel-protective-role-of-nicotinamide-phosphoribosyltransferase-in-acetaminophen-induced-acute-liver-injury-in-mice
#7
Li Qin Zhang, Marianne Nsumu, Peixin Huang, Daniel P Heruth, Sean M Riordan, Katherine Shortt, Nini Zhang, Dmitry N Grigoryev, Ding-You Li, Craig A Friesen, Leon Van Haandel, J Steven Leeder, Jody Olson, Shui Qing Ye
Acetaminophen overdose is the most common cause of acute liver injury (ALI) or acute liver failure in the US. Its pathogenetic mechanisms are incompletely understood. Additional studies are warranted to identify new genetic risk factors for more mechanistic insights and new therapeutic target discoveries. The objective of this study was to explore the role and mechanisms of nicotinamide phosphoribosyltransferase (NAMPT) in acetaminophen-induced ALI. C57BL/6 Nampt gene wild-type (Nampt+/+ )-, heterozygous knockout (Nampt+/- )-, and overexpression (NamptOE )-mice were treated with overdose of acetaminophen, followed by histological, biochemical, and transcriptomic evaluation of liver injury...
April 20, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29667370/systems-toxicology-approach-to-identifying-paracetamol-overdose
#8
Chantelle L Mason, Joseph Leedale, Sotiris Tasoulis, Ian Jarman, Daniel J Antoine, Steven D Webb
Paracetamol (acetaminophen (APAP)) is one of the most commonly used analgesics in the United Kingdom and the United States. However, exceeding the maximum recommended dose can cause serious liver injury and even death. Promising APAP toxicity biomarkers are thought to add value to those used currently and clarification of the functional relationships between these biomarkers and liver injury would aid clinical implementation of an improved APAP toxicity identification framework. The framework currently used to define an APAP overdose is highly dependent upon time since ingestion and initial dose; information that is often highly unpredictable...
April 18, 2018: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/29617548/calculated-decisions-king-s-college-criteria-for-acetaminophen-toxicity
#9
Vincent Nguyen
No abstract text is available yet for this article.
April 1, 2018: Emergency Medicine Practice
https://www.readbyqxmd.com/read/29614487/prevalence-of-hypersensitivity-reactions-in-children-associated-with-acetaminophen-a-systematic-review-and-meta-analysis
#10
Sofianne Gabrielli, Alexandra Langlois, Moshe Ben-Shoshan
BACKGROUND: Acetaminophen is the most commonly used antipyretic in children. However, there are limited data assessing hypersensitivity reactions related to acetaminophen usage. OBJECTIVES: To conduct a systematic review to characterize reported reactions to acetaminophen in adults and children, and perform a meta-analysis to assess the prevalence of acetaminophen hypersensitivity in children with a suspected acetaminophen allergy. METHODS: We performed a systematic review of studies reporting hypersensitivity reactions to acetaminophen by searching 2 electronic databases...
April 3, 2018: International Archives of Allergy and Immunology
https://www.readbyqxmd.com/read/29605069/acetaminophen-apap-or-n-acetyl-p-aminophenol-and-acute-liver-failure
#11
REVIEW
Chalermrat Bunchorntavakul, K Rajender Reddy
Acetaminophen (APAP) is the leading cause of acute liver failure (ALF), although the worldwide frequency is variable. APAP hepatotoxicity develops either following intentional overdose or unintentional ingestion (therapeutic misadventure) in the background of several factors, such as concomitant use of alcohol and certain medications that facilitate the formation of reactive and toxic metabolites. Spontaneous survival is more common in APAP-induced ALF compared with non-APAP etiologies. N-acetylcysteine is recommended for all patients with APAP-induced ALF and it reduces mortality...
May 2018: Clinics in Liver Disease
https://www.readbyqxmd.com/read/29574134/assessment-of-n-acetylcysteine-as-a-therapy-for-phosgene-induced-acute-lung-injury
#12
Rachel Rendell, Sarah Fairhall, Stuart Graham, Steve Rutter, Philippa Auton, Adam Smith, Rosi Perrott, Bronwen Jugg
The toxic industrial chemical (TIC1 ) phosgene remains an important chemical intermediate in many industrial processes. Inhalation of phosgene can cause an acute lung injury (ALI) which, in severe cases may result in death. There are currently no effective pharmacological therapies or evidence-based treatment guidelines for managing exposed individuals. N-acetylcysteine (NAC) is a commercially available drug licensed in the UK and elsewhere for the treatment of paracetamol (acetaminophen) overdose. It has a number of mechanisms of action which may provide therapeutic benefit for the treatment of phosgene-induced ALI...
March 21, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29569740/the-medication-risk-of-stevens-johnson-syndrome-and-toxic-epidermal-necrolysis-in-asians-the-major-drug-causality-and-comparison-to-the-usa-fda-label
#13
Yu-Hsin Wang, Chun-Bing Chen, Wichittra Tassaneeyakul, Yoshiro Saito, Michiko Aihara, Siew Eng Choon, Haur Yueh Lee, Mimi Mee Chang, Francisca D Roa, Cheng-Wei Wu, Jing Zhang, Nontaya Nakkam, Parinya Konyoung, Yoshimi Okamoto-Uchida, Christina Man-Tung Cheung, Jin-Wen Huang, Chao Ji, Bo Cheng, Rosaline Chung-Yee Hui, Chia-Yu Chu, Yi-Ju Chen, Ching-Ying Wu, Chao-Kai Hsu, Tsu-Man Chiu, Hsin-Chun Ho, Jing-Yi Lin, Chih-Hsun Yang, Ya-Ching Chang, Shih-Chi Su, Chuang Wei Wang, Wen-Hung Chung
Specific ethnic genetic backgrounds associated with risk of Stevens-Johnson syndrome/toxic epidermal necrolysis(SJS/TEN) especially in Asians. However, there have been no large cohort, multiple-country epidemiological studies of medication risk related to SJS/TEN in Asian populations. Thus, we analyzed the registration databases from multiple Asian countries who were treated during 1998-2017. A total 1028 SJS/TEN cases were identified by ALDEN. Furthermore, those medications labeled by USFDA as carrying a risk of SJS/TEN were also compared to the common causes of SJS/TEN in Asian countries...
March 23, 2018: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29560444/ethyl-pyruvate-attenuates-acetaminophen-induced-liver-injury-and-prevents-cellular-injury-induced-by-n-acetyl-p-benzoquinone-imine
#14
Minako Nagatome, Yuki Kondo, Daisuke Kadowaki, Yusuke Saishyo, Mitsuru Irikura, Tetsumi Irie, Yoichi Ishitsuka
Acetaminophen, a common analgesic/antipyretic, is a frequent cause of acute liver failure in Western countries. The development of an effective cure against acetaminophen hepatotoxicity is crucial. Ethyl pyruvate, an ethyl ester derivative of pyruvic acid, has been identified as a possible candidate against acetaminophen hepatotoxicity in animal experiments. However, the mode of the hepatoprotective action of ethyl pyruvate remains unclear. We examined the hepatoprotective effect of ethyl pyruvate against hepatocyte injury and oxidative stress in a mouse model of acetaminophen hepatotoxicity...
February 2018: Heliyon
https://www.readbyqxmd.com/read/29543727/microscale-3d-liver-bioreactor-for-in-vitro-hepatotoxicity-testing-under-perfusion-conditions
#15
Nora Freyer, Selina Greuel, Fanny Knöspel, Florian Gerstmann, Lisa Storch, Georg Damm, Daniel Seehofer, Jennifer Foster Harris, Rashi Iyer, Frank Schubert, Katrin Zeilinger
The accurate prediction of hepatotoxicity demands validated human in vitro models that can close the gap between preclinical animal studies and clinical trials. In this study we investigated the response of primary human liver cells to toxic drug exposure in a perfused microscale 3D liver bioreactor. The cellularized bioreactors were treated with 5, 10, or 30 mM acetaminophen (APAP) used as a reference substance. Lactate production significantly decreased upon treatment with 30 mM APAP ( p < 0.05) and ammonia release significantly increased in bioreactors treated with 10 or 30 mM APAP ( p < 0...
March 15, 2018: Bioengineering
https://www.readbyqxmd.com/read/29540258/dna-damage-response-regulates-initiation-of-liver-regeneration-following-acetaminophen-overdose
#16
Prachi Borude, Bharat Bhushan, Udayan Apte
Acetaminophen (APAP) overdose is the leading cause of Acute Liver Failure (ALF) with limited treatment options. It is known that liver regeneration following APAP induced ALF is a deciding factor in the final outcome. Previous studies from our laboratory using incremental dose model involving a regenerating (300 mg/kg, APAP300) and a non-regenerating (600 mg/kg, APAP600) dose of APAP in mice have revealed several pro- regenerative pathways that regulate regeneration after APAP overdose. Here we report that DNA damage and repair mechanisms regulate initiation liver regeneration following APAP overdose...
March 14, 2018: Gene Expression
https://www.readbyqxmd.com/read/29536760/letter-in-reply-to-levine-et-al-re-hypoglycemia-and-lactic-acidosis-outperform-king-s-college-criteria-for-predicting-death-or-transplant-in-acetaminophen-toxic-patients
#17
Jeremy Brice Bitton, Josh Jiaxing Wang, Winnie Teng, Eric Villeneuve, Sophie Gosselin
No abstract text is available yet for this article.
March 14, 2018: Clinical Toxicology
https://www.readbyqxmd.com/read/29512171/exogenous-recombinant-human-thioredoxin-1-prevents-acetaminophen-induced-liver-injury-by-scavenging-oxidative-stressors-restoring-the-thioredoxin-1-system-and-inhibiting-receptor-interacting-protein-3-overexpression
#18
Byung-Woo Lee, Byung-Suk Jeon, Byung-Il Yoon
Thioredoxin-1 (Trx-1) is a potent therapeutic agent against a variety of diseases because of its actions as an antioxidant and regulator of apoptosis. N-acetyl-p-aminophenol (APAP), commonly known as acetaminophen, generates excessive oxidative stress and triggers hepatocyte cell death, exemplified by regulated necrosis. In the present study, we investigated whether APAP-induced liver injury in a mouse model is associated with "necroptosis," and if pretreatment with recombinant Trx-1 prevents the hepatic injury caused by APAP overdose...
March 7, 2018: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/29511414/histologic-characterization-of-kratom-use-associated-liver-injury
#19
Michael Riverso, Michael Chang, Consuelo Soldevila-Pico, Jinping Lai, Xiuli Liu
Kratom is an herbal product derived from the leaves of Southeast Asian Mitragyna speciosa trees. It has traditionally been used by indigenous people to relieve fatigue and manage pain, diarrhea, or opioid withdrawal. The use of kratom has become more commonplace in the United States for similar purposes. Only rare reports of kratom liver toxicity exist in the literature but without histologic characterization. Herein, we report one case of kratom use-associated liver toxicity in a 38-year-old patient. The patient complained of dark colored urine and light colored stools after using kratom...
February 2018: Gastroenterology Research
https://www.readbyqxmd.com/read/29504225/replicative-stress-and-alterations-in-cell-cycle-checkpoint-controls-following-acetaminophen-hepatotoxicity-restrict-liver-regeneration
#20
Preeti Viswanathan, Yogeshwar Sharma, Priya Gupta, Sanjeev Gupta
OBJECTIVES: Acetaminophen hepatotoxicity is a leading cause of hepatic failure with impairments in liver regeneration producing significant mortality. Multiple intracellular events, including oxidative stress, mitochondrial damage, inflammation, etc., signify acetaminophen toxicity, although how these may alter cell cycle controls has been unknown and was studied for its significance in liver regeneration. MATERIALS AND METHODS: Assays were performed in HuH-7 human hepatocellular carcinoma cells, primary human hepatocytes and tissue samples from people with acetaminophen-induced acute liver failure...
March 5, 2018: Cell Proliferation
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