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Acetaminophen toxicity

Robim M Rodrigues, Olivier Govaere, Tania Roskams, Tamara Vanhaecke, Vera Rogiers, Joery De Kock
This data set is composed of transcriptomics analyses of (i) liver samples from patients suffering from acetaminophen-induced acute liver failure (ALF) and (ii) hepatic cell systems exposed to acetaminophen and their respective controls. The in vitro systems include widely employed cell lines i.e. HepaRG and HepG2 cells as well as a novel stem cell-derived model i.e. human skin-precursors-derived hepatocyte-like cells (hSKP-HPC). Data from primary human hepatocytes was also added to the data set "Open TG-GATEs: a large-scale toxicogenomics database" (Igarashi et al...
June 2016: Data in Brief
Dushani L Palliyaguru, Dionysios V Chartoumpekis, Nobunao Wakabayashi, John J Skoko, Yoko Yagishita, Shivendra V Singh, Thomas W Kensler
Small molecules of plant origin offer presumptively safe opportunities to prevent carcinogenesis, mutagenesis and other forms of toxicity in humans. However, the mechanisms of action of such plant-based agents remain largely unknown. In recent years the stress responsive transcription factor Nrf2 has been validated as a target for disease chemoprevention. Withania somnifera (WS) is a herb used in Ayurveda (an ancient form of medicine in South Asia). In the recent past, withanolides isolated from WS, such as Withaferin A (WA) have been demonstrated to be preventive and therapeutic against multiple diseases in experimental models...
October 4, 2016: Free Radical Biology & Medicine
Arun Tailor, James C Waddington, Xiaoli Meng, B Kevin Park
The covalent binding of drugs (metabolites) to proteins to form drug-protein adducts can have an adverse effect on the body. These adducts are thought to be responsible for idiosyncratic drug reactions including severe drug hypersensitivity reactions. Major advances in proteomics technology have allowed for the identification and quantification of target proteins for certain drugs. Human serum albumin (HSA) and Hb have been identified as accessible targets and potential biomarkers for drug-protein adducts formation, for numerous drugs (metabolites) including β-lactam antibiotics, reactive drug metabolites such as quinone imines (acetaminophen) and acyl glucuronides (diclofenac), and covalent inhibitors (neratinib)...
September 30, 2016: Chemical Research in Toxicology
Antonin Azaïs, Julie Mendret, Eddy Petit, Stephan Brosillon
Global population growth induces increased threat on drinking water resources. One way to address this environmental issue is to reuse water from wastewater treatment plant. The presence of pathogenic microorganisms and potentially toxic organic micropollutants does not allow a direct reuse of urban effluents. Membrane processes such reverse osmosis (RO) or nanofiltration (NF) can be considered to effectively eliminate these pollutants. The integration of membrane processes involves the production of concentrated retentates which require being disposed...
December 2016: Chemosphere
Yakov M Koen, Ke Liu, Heather Shinogle, Todd D Williams, Robert P Hanzlik
The hepatotoxicity of acetaminophen (APAP) is generally attributed to the formation of a reactive quinoneimine metabolite (NAPQI) that depletes glutathione and covalently binds to hepatocellular proteins. To explore the importance of the N-acyl group in APAP metabolism and toxicity, we synthesized 12 acyl side chain homologues of acetaminophen (APAP) and its 3'-regioisomer (AMAP), including the respective N-(4-pentynoyl) analogues PYPAP and PYMAP. Rat hepatocytes converted APAP, AMAP, PYPAP, and PYMAP extensively to O-glucuronide and O-sulfate conjugates in varying proportions, whereas glutathione or cysteine conjugates were observed only for APAP and PYPAP...
October 13, 2016: Chemical Research in Toxicology
Maranda Esterhuizen-Londt, Katrin Schwartz, Stephan Pflugmacher
The increasing anthropogenic pollution of aquatic environments and fresh water scarcity worldwide have prompted the development of low-cost and effective water treatment alternatives. One example of a highly released anthropogenic xenobiotics is acetaminophen (APAP), which has been detected in surface waters at concentrations as high as 5 μg L(-1). To date, traditional water treatment plants were unable to remove all pharmaceutical xenobiotics and as in the case with APAP, the breakdown products are toxic...
October 2016: Fungal Biology
Dean W Roberts, William M Lee, Jack A Hinson, Shasha Bai, Christopher J Swearingen, R Todd Stravitz, Adrian Reuben, Lynda Letzig, Pippa M Simpson, Jody Rule, Robert J Fontana, Daniel Ganger, K Rajender Reddy, Iris Liou, Oren Fix, Laura P James
BACKGROUND & AIMS: A rapid, reliable point-of-care assay to detect acetaminophen protein adducts in serum of patients with acute liver injury could improve diagnosis and management. AcetaSTAT is a competitive immunoassay used to measure acetaminophen protein adducts formed by toxic metabolites in serum samples from patients. We compared the accuracy of AcetaSTAT vs high-pressure liquid chromatography with electrochemical detection (HPLC-EC, a sensitive and specific quantitative analytical assay) to detect acetaminophen protein adducts...
September 15, 2016: Clinical Gastroenterology and Hepatology
James P Sluka, Xiao Fu, Maciej Swat, Julio M Belmonte, Alin Cosmanescu, Sherry G Clendenon, John F Wambaugh, James A Glazier
We describe a multi-scale, liver-centric in silico modeling framework for acetaminophen pharmacology and metabolism. We focus on a computational model to characterize whole body uptake and clearance, liver transport and phase I and phase II metabolism. We do this by incorporating sub-models that span three scales; Physiologically Based Pharmacokinetic (PBPK) modeling of acetaminophen uptake and distribution at the whole body level, cell and blood flow modeling at the tissue/organ level and metabolism at the sub-cellular level...
2016: PloS One
Yuan Gao, Zhijun Cao, Xi Yang, Mohamed A Abdelmegeed, Jinchun Sun, Si Chen, Richard D Beger, Kelly Davis, William F Salminen, Byoung-Joon Song, Donna L Mendrick, Li-Rong Yu
Overdose of acetaminophen (APAP) is a major cause of acute liver failure. To identify pathways related to hepatotoxicity and potential biomarkers of liver injury, a proteomic approach of (16) O/(18) O labeling and 2D-LC-MS/MS was used to analyze liver tissues from rats at 6 and 24 h post-treatment with low (100 mg/kg) and high (1250 mg/kg) doses of APAP. The analysis revealed that molecular pathways evolved progressively from scattered and less significant perturbations to more focused and significant alterations in a dose- and time-dependent manner...
September 16, 2016: Proteomics. Clinical Applications
Joshua B Smith, Kelsey L Turner, James C Beasley, Travis L DeVault, William C Pitt, Olin E Rhodes
Mass aerial delivery of dead mouse baits treated with acetaminophen has been evaluated as a means to reduce brown tree snake (Boiga irregularis) populations over large areas, increasing the likelihood of wide-scale eradication on Guam. Given the high density of snakes in some areas of their invasive range, eradication efforts could result in a resource pulse that may influence food web dynamics and the indirect transport of acetaminophen among trophic levels. We evaluated abundance, habitat type, and snake size (i...
September 7, 2016: Ecotoxicology
Mustafa Ferudun Çelikmen, Sezgin Sarıkaya, Doğaç Niyazi Özüçelik, Mehmet Şükrü Sever, Kurtuluş Açıksarı, Deniz Maktav Çelikmen, Mustafa Yazıcıoğlu, Ali Kandemir, Halil Doğan, Barış Murat Ayvacı, Derya Özaşır Abuşka, Sıla Sadıllıoğlu
BACKGROUND: The present objective was to evaluate effects of acetaminophen and mannitol on renal function and histopathology in crush injuries. METHODS: Thirty-six rats weighing 370-400 g each were used. No surgery was performed on the first (control) group. The gastrocnemius muscle regions of each rat in the remaining 5 groups were compressed for 2 or 24 hours. In the 4th group, 100 mg/kg acetaminophen was intraperitoneally administered. In the 5th group, 1 g/kg mannitol was administered...
July 2016: Ulusal Travma Ve Acil Cerrahi Dergisi, Turkish Journal of Trauma & Emergency Surgery: TJTES
Jimmy Donkor, Patil Armenian, Isaac N Hartman, Rais Vohra
BACKGROUND: As decontamination trends have evolved, gastric lavage (GL) has become a rare procedure. The current information regarding use, outcomes, and complications of GL could help refine indications for this invasive procedure. OBJECTIVES: We sought to determine case type, location, and complications of GL cases reported to a statewide poison control system. METHODS: This is a retrospective review of the California Poison Control System (CPCS) records from 2009 to 2012...
October 2016: Journal of Emergency Medicine
Ryo Koyama, Ryushin Mizuta
Our previous study suggested that the highly toxic α,β-unsaturated aldehyde acrolein, a byproduct of oxidative stress, plays a major role in acetaminophen-induced liver injury. In this study, to determine the involvement of acrolein in the liver injury and to identify novel therapeutic options for the liver damage, we examined two putative acrolein scavengers, a thiol compound cysteamine and a hydroxylamine N-benzylhydroxylamine, in cell culture and in mice. Our results showed that cysteamine and N-benzylhydroxylamine effectively prevented the cell toxicity of acrolein in vitro and acetaminophen-induced liver injury in vivo, which suggested that acrolein is involved in the liver damage, and these two drugs can be potential therapeutic options for this condition...
September 5, 2016: Journal of Veterinary Medical Science
Hongtao Lu, Zhiliang Zhu, Hua Zhang, Jianyao Zhu, Yanling Qiu, Linyan Zhu, Stephan Küppers
Acetaminophen can increase the risk of arsenic-mediated hepatic oxidative damage; therefore, the decontamination of water polluted with coexisting acetaminophen and arsenic gives rise to new challenges for the purification of drinking water. In this work, a three-metal layered double hydroxide, namely, Cu-Zn-Fe-LDH, was synthesized and applied as a heterogeneous Fenton-like oxidation catalyst and adsorbent to simultaneously remove acetaminophen (Paracetamol, PR) and arsenic. The results showed that the degradation of acetaminophen was accelerated with decreasing pH or increasing H2O2 concentrations...
September 28, 2016: ACS Applied Materials & Interfaces
Ga-Young Ban, Seun-Joo Ahn, Hye-Soo Yoo, Hae-Sim Park, Young-Min Ye
An association between drug treatment for viral infections and severe cutaneous adverse reactions has been noted. We investigated six patients diagnosed with Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) after being prescribed acetaminophen for suspected viral illnesses. Multiplex analysis was performed to measure cytokine levels in sera before and after treatment. IL-2Rα levels significantly decreased during the convalescence phase. Although acetaminophen is relatively safe, the drug can trigger SJS/TEN in patients with suspected viral infections...
August 2016: Immune Network
Mesfin Yimam, Ping Jiao, Mei Hong, Qi Jia
Historically, botanicals have been reported to possess good antioxidative activities as demonstrated by their free radical scavenging property rendering their usage in liver protection. In this study, we describe the potential use of MAP, a standardized blend comprising three extracts from Myristica fragrans, Astragalus membranaceus, and Poria cocos, in ameliorating chemically induced acute liver toxicities. Acetaminophen (APAP) and carbon tetrachloride (CCl4)-induced acute liver toxicity models in mice were utilized...
August 26, 2016: Journal of Medicinal Food
Hyun-Sik Nam, Kyu-Seok Hwang, Yun-Mi Jeong, Jeong-Im Ryu, Tae-Young Choi, Myung-Ae Bae, Woo-Chan Son, Kwan-Hee You, Hwa-Young Son, Cheol-Hee Kim
MicroRNA-122 (miRNA-122), also known as liver-specific miRNA, has recently been shown to be a potent biomarker in response to liver injury in mammals. The objective of this study was to examine its expression in response to toxicant treatment and acute liver damage, using the zebrafish system as an alternative model organism. For the hepatotoxicity assay, larval zebrafish were arrayed in 24-well plates. Adult zebrafish were also tested and arrayed in 200 mL cages. Animals were exposed to liver toxicants (tamoxifen or acetaminophen) at various doses, and miRNA-122 expression levels were analyzed using qRT-PCR in dissected liver, brain, heart, and intestine, separately...
2016: BioMed Research International
Natarajan Karikalan, Raj Karthik, Shen-Ming Chen, Murugan Velmurugan, Chelladurai Karuppiah
Acetaminophen is a non-steroidal anti-inflammatory drug used as an antipyretic agent for the alternative to aspirin. Conversely, the overdoses of acetaminophen can cause hepatic toxicity and kidney damage. Hence, the determination of acetaminophen receives much more attention in biological samples and also in pharmaceutical formulations. Here, we report a rapid and sensitive detection of the acetaminophen based on the bare (unmodified) screen printed carbon electrode (BSPCE) and its electrochemistry was studied in various pHs...
December 1, 2016: Journal of Colloid and Interface Science
Swetha Rudraiah, José E Manautou
A variety of rodent models of hepatoprotection have been developed in which tolerance to acetaminophen-induced hepatotoxicity occurs. Autoprotection/heteroprotection is a phenomenon where prior exposure to a mildly toxic dose of toxicant confers protection against a subsequently administered higher dose of the same toxicant (as in the case of autoprotection) or to a different toxicant (referred to as heteroprotection). Multiple mechanisms regulate this adaptive response, including hepatocellular proliferation, proteostasis, enhanced expression of cytoprotective genes, and altered tissue immune response...
2016: F1000Research
Chelsey M McPheeters, Vanessa M VanArsdale, Kyle A Weant
This article will review the available evidence related to the management of non-acetaminophen induced acute liver failure with N-acetylcysteine. Randomized controlled trials and a meta-analysis were included in this review. The efficacy of N-acetylcysteine in the treatment of acute liver failure from causes other than acetaminophen toxicity was evaluated. The efficacy of N-acetylcysteine in non-acetaminophen-induced acute liver failure is limited to specific patient populations. Patients classified as Coma Grade I or II are more likely to benefit from the use of this agent...
July 2016: Advanced Emergency Nursing Journal
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