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https://www.readbyqxmd.com/read/29350208/protective-effect-of-paracetamol-in-doxorubicin-induced-cardiotoxicity-in-ischemia-reperfused-isolated-rat-heart
#1
Mahvash Hesari, Dareuosh Shackebaei, Atefeh Asadmobini
OBJECTIVE: Doxorubicin (DOX) induces cardiac dysfunction. Paracetamol (APAP) has also been established as an effective cardioprotective agent during ischemia/reperfusion. Therefore, this study aims to evaluate the effect of APAP on DOX-induced cardiotoxicity in ischemia/reperfused isolated rat heart. METHODS: A total of 36 rats were equally divided into four groups: control, DOX (30 min, 20 µM DOX perfusion), APAP (15 min before and after ischemia, 0.35 mM APAP perfusion), and DOX+APAP (perfused with the same protocol in DOX and APAP groups)...
January 19, 2018: Anatolian Journal of Cardiology
https://www.readbyqxmd.com/read/29342206/silymarin-prevents-acetaminophen-induced-hepatotoxicity-in-mice
#2
Zuzana Papackova, Marie Heczkova, Helena Dankova, Eva Sticova, Alena Lodererova, Lenka Bartonova, Martin Poruba, Monika Cahova
Acetaminophen or paracetamol (APAP) overdose is a common cause of liver injury. Silymarin (SLM) is a hepatoprotective agent widely used for treating liver injury of different origin. In order to evaluate the possible beneficial effects of SLM, Balb/c mice were pretreated with SLM (100 mg/kg b.wt. per os) once daily for three days. Two hours after the last SLM dose, the mice were administered APAP (300 mg/kg b.wt. i.p.) and killed 6 (T6), 12 (T12) and 24 (T24) hours later. SLM-treated mice exhibited a significant reduction in APAP-induced liver injury, assessed according to AST and ALT release and histological examination...
2018: PloS One
https://www.readbyqxmd.com/read/29341895/prenatal-paracetamol-exposure-and-child-neurodevelopment-a-review
#3
REVIEW
Ann Z Bauer, David Kriebel, Martha R Herbert, Carl-Gustaf Bornehag, Shanna H Swan
BACKGROUND: The non-prescription medication paracetamol (acetaminophen, APAP) is currently recommended as a safe pain and fever treatment during pregnancy. However, recent studies suggest a possible association between APAP use in pregnancy and offspring neurodevelopment. OBJECTIVES: To conduct a review of publications reporting associations between prenatal APAP use and offspring neurodevelopmental outcomes. METHODS: Relevant sources were identified through a key word search of multiple databases (Medline, CINAHL, OVID and TOXNET) in September 2016...
January 13, 2018: Hormones and Behavior
https://www.readbyqxmd.com/read/29338970/baicalein-and-baicalin-alleviate-acetaminophen-induced-liver-injury-by-activating-nrf2-antioxidative-pathway-the-involvement-of-erk1-2-and-pkc
#4
Liang Shi, Zhanxia Hao, Shaobo Zhang, Mengjuan Wei, Bin Lu, Zhengtao Wang, Lili Ji
Acetaminophen (APAP)-induced hepatotoxicity is the main cause of drug-induced liver injury. This study investigated the protection of baicalin and its aglycone baicalein against APAP-induced hepatotoxicity and its mechanism. Baicalein and baicalin alleviated APAP-induced hepatotoxicity both in vitro and in vivo. Moreover, baicalin-provided this protection was not diminished in hepatocytes or mice treated with β-glucuronidase inhibitor. Results of liver glutathione (GSH) and reactive oxygen species (ROS) formation demonstrated the alleviation of baicalein and baicalin on APAP-induced liver oxidative stress injury...
January 12, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29334775/resistance-to-acetaminophen-interference-in-a-novel-continuous-glucose-monitoring-system
#5
Peter Calhoun, Terri Kang Johnson, Jonathan Hughes, David Price, Andrew K Balo
Acetaminophen (APAP) can cause erroneously high readings in real-time continuous glucose monitoring (rtCGM) systems. APAP-associated bias in an investigational rtCGM system (G6) was evaluated by taking the difference in glucose measurements between rtCGM and YSI from 1 hour before to 6 hours after a 1-g oral APAP dose in 66 subjects with type 1 or type 2 diabetes. The interference effect was defined as the average post-dose (30-90 minutes) bias minus the average baseline bias for each subject. The clinically meaningful interference effect was defined as 10 mg/dL...
January 1, 2018: Journal of Diabetes Science and Technology
https://www.readbyqxmd.com/read/29331651/activation-of-p62-keap1-nrf2-antioxidant-pathway-in-the-early-stage-of-acetaminophen-induced-acute-liver-injury-in-mice
#6
Zhenyu Shen, Yu Wang, Zhenhui Su, Ruirui Kou, Keqin Xie, Fuyong Song
Acetaminophen (APAP) overdose can cause severe liver failure even death. Nearly half of drug-induced liver injury is attributed to APAP in the US and many European countries. Oxidative stress has been validated as a critical event involved in APAP-induced liver failure. p62/SQSTM1, a selective autophagy adaptor protein, is reported to regulate Nrf2-ARE antioxidant pathway in response to oxidative stress. However, the exact role of p62-keap1-Nrf2 antioxidant pathway in APAP-induced hepatotoxicity remains unknown...
January 10, 2018: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29331486/prenatal-exposure-to-acetaminophen-and-children-s-language-development-at-30-months
#7
C-G Bornehag, A Reichenberg, M Unenge Hallerback, S Wikstrom, H M Koch, B A Jonsson, S H Swan
OBJECTIVE: To examine prenatal APAP exposure in relation to language development in offspring at 30 months of age. METHOD: A population-based pregnancy cohort study including 754 women who enrolled in the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy (SELMA) study in pregnancy week 8-13. Two exposure measures were used: (1) maternally reported number of APAP tablets taken between conception and enrollment; (2) APAP urinary concentration at enrollment...
November 10, 2017: European Psychiatry: the Journal of the Association of European Psychiatrists
https://www.readbyqxmd.com/read/29331340/hsp72-protects-from-liver-injury-via-attenuation-of-hepatocellular-death-oxidative-stress-and-jnk-signaling
#8
Kateryna Levada, Nurdan Guldiken, Xiaoji Zhang, Giovanna Vella, Fa-Rong Mo, Laura P James, Johannes Haybaeck, Sonja M Kessler, Alexandra K Kiemer, Thomas Ott, Daniel Hartmann, Norbert Hüser, Marianne Ziol, Christian Trautwein, Pavel Strnad
BACKGROUND AND AIMS: Heat shock protein (Hsp) 72 is a molecular chaperone that is upregulated in response to stress and possesses broad cytoprotective functions. To determine its hepatic function, we studied its expression in human liver disorders and its biological significance in newly generated transgenic animals. AIM AND METHODS: Double transgenic mice overexpressing Hsp72 (gene HSPA1A) under the control of a tissue-specific tetracycline-inducible system (Hsp72-LAP mice) were produced...
January 10, 2018: Journal of Hepatology
https://www.readbyqxmd.com/read/29328974/novel-approach-for-evaluating-pharmaceuticals-toxicity-using-daphnia-model-analysis-of-the-mode-of-cytochrome-p450-generated-metabolite-action-after-acetaminophen-exposure
#9
Ryeo-Ok Kim, Min-A Jo, Jinhaeng Song, Il-Chan Kim, Seokjoo Yoon, Woo-Keun Kim
Because of its widespread use, the pharmaceutical acetaminophen (APAP) is frequently detected in aquatic environments. APAP can have serious physiological effects, such as reduced reproduction, low growth rates, and abnormal behavior, in aquatic organisms. However, the methods available for evaluation of the aquatic toxicity of APAP are of limited usefulness. The present study aimed to develop reliable and sensitive markers for evaluation of APAP toxicity using Daphnia as a model organism. We focused on N-acetyl-p-benzoquinoneimine (NAPQI) production from APAP via cytochrome P450 metabolism because NAPQI causes APAP toxicity...
December 30, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/29325178/modulation-of-o-glcnac-levels-in-the-liver-impacts-acetaminophen-induced-liver-injury-by-affecting-protein-adduct-formation-and-glutathione-synthesis
#10
Steven R McGreal, Bharat Bhushan, Chad Walesky, Mitchell R McGill, Margitta Lebofsky, Sylvie E Kandel, Robert D Winefield, Hartmut Jaeschke, Natasha E Zachara, Zhen Zhang, Ee Phie Tan, Chad Slawson, Udayan Apte
Overdose of acetaminophen (APAP) results in acute liver failure. We have investigated the role of a post-translational modification of proteins called O-GlcNAcylation, where the O-GlcNAc transferase (OGT) adds and O-GlcNAcase (OGA) removes a single β-D-N-acetylglucosamine (O-GlcNAc) moiety, in the pathogenesis of APAP-induced liver injury. Hepatocyte specific OGT knockout mice (OGT KO), which have reduced O-GlcNAcylation, and WT controls were treated with 300 mg/kg APAP and the development of injury was studied over a time course from 0-24 hr...
January 9, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29317025/electrochemical-sensing-platform-based-on-kelp-derived-hierarchical-meso-macroporous-carbons
#11
Yashuang Hei, Xiqian Li, Xiao Zhou, Jingju Liu, Mimi Sun, Tianze Sha, Cuixing Xu, Wanyi Xue, Xiangjie Bo, Ming Zhou
In this paper, kelp (Laminaria japonica), as a kind of abundant biomass, is used as the precursor for the preparation of kelp-derived hierarchical meso-macroporous carbons (K-dHMMCs) through the carbonization under nitrogen (N2) atmosphere at high temperature. The K-dHMMCs exhibits the unique structure with high specific surface area of 416.02 m2 g-1, large pore volume of 0.24 cm3 g-1, the hierarchical meso-macroporous size distribution centered at 2, 12 and 82 nm and high density of defective sites, enabling K-dHMMCs attractive for the electrocatalysis...
March 20, 2018: Analytica Chimica Acta
https://www.readbyqxmd.com/read/29310687/long-term-mortality-of-acetaminophen-poisoning-a-nationwide-population-based-cohort-study-with-10-year-follow-up-in-taiwan
#12
Hung-Sheng Huang, Chung-Han Ho, Shih-Feng Weng, Chien-Chin Hsu, Jhi-Joung Wang, Shih-Bin Su, Hung-Jung Lin, Chien-Cheng Huang
BACKGROUND: The long-term mortality of acetaminophen (APAP) poisoning has not yet been well studied; hence, we conducted this study to gain understanding of this issue. METHODS: We conducted a nationwide population-based cohort study by identifying 3235 participants with APAP poisoning and 9705 participants without APAP poisoning in Taiwan between 2003 and 2012 in the Nationwide Poisoning Database and Longitudinal Health Insurance Database 2000. Participants with APAP poisoning and control subjects were compared for the risk of all-cause mortality by follow-up until 2013...
January 8, 2018: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine
https://www.readbyqxmd.com/read/29306760/effect-of-acetaminophen-on-osteoblastic-differentiation-and-migration-of-mc3t3-e1-cells
#13
Yoshihiro Nakatsu, Fumio Nakagawa, Sen Higashi, Tomoko Ohsumi, Shunji Shiiba, Seiji Watanabe, Hiroshi Takeuchi
BACKGROUND: N-acetyl-p-aminophenol (APAP, acetaminophen, paracetamol) is a widely used analgesic/antipyretic with weak inhibitory effects on cyclooxygenase (COX) compared to non-steroidal anti-inflammatory drugs (NSAIDs). The mechanism of action of APAP is mediated by its metabolite that activates transient receptor potential channels, including transient receptor potential vanilloid 1 (TRPV1) and TRP ankyrin 1 (TRPA1) or the cannabinoid receptor type 1 (CB1). However, the exact molecular mechanism and target underlying the cellular actions of APAP remain unclear...
July 15, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/29305717/influence-of-low-molecular-weight-excipients-on-the-phase-behavior-of-pvpva64-amorphous-solid-dispersions
#14
Kristin Lehmkemper, Samuel O Kyeremateng, Matthias Degenhardt, Gabriele Sadowski
PURPOSE: The oral bioavailability of poorly water-soluble active pharmaceutical ingredients (APIs) can be improved by the preparation of amorphous solid dispersions (ASDs) where the API is dissolved in polymeric excipients. Desired properties of such ASDs like storage stability, dissolution behavior, and processability can be optimized by additional excipients. In this work, the influence of so-called low-molecular-weight excipients (LMWEs) on the phase behavior of ASDs was investigated...
January 5, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/29302859/acetaminophen-poisoning-may-increase-coronary-artery-disease-risk-a-nationwide-cohort-study
#15
Yu-Ting Chung, Che-Yi Chou, Wen-Chen Tsai, Wei-Kung Chen, Cheng-Li Lin, Wei-Sheng Chung
The purpose of this nationwide cohort study was to investigate the incidence and risk of coronary artery disease (CAD) in patients with acetaminophen (APAP) poisoning. We identified the patients with APAP poisoning and randomly selected comparison patients according to a 1:4 ratio, matching them by age, sex, and the index year using data from the National Health Insurance Research Database from 2000 to 2010. We traced both cohorts until a diagnosis of CAD, loss to follow-up, or the end of 2011. In total, 2723 patients with APAP poisoning and 10,892 comparison patients have followed...
January 4, 2018: Cardiovascular Toxicology
https://www.readbyqxmd.com/read/29298664/the-prevention-of-delirium-in-elderly-with-obstructive-sleep-apnea-podesa-study-protocol-for-a-multi-centre-prospective-randomized-controlled-trial
#16
Jean Wong, David Lam, Stephen Choi, Mandeep Singh, Naveed Siddiqui, Sanjeev Sockalingam, Frances Chung
BACKGROUND: Delirium is a common problem that occurs in 5-50% of elderly individuals following surgery. Patients who develop delirium after surgery are at increased risk for serious complications. Recent studies suggest that patients with obstructive sleep apnea (OSA), a sleep disorder characterized by repeated episodes of complete or partial blockage of the upper airway - are at greater risk to develop delirium. OSA is more common in elderly individuals but is often undiagnosed. Identification and treatment of unrecognized OSA may reduce the incidence of postoperative delirium...
January 3, 2018: BMC Anesthesiology
https://www.readbyqxmd.com/read/29287080/serum-apolipoprotein-a1-and-haptoglobin-in-patients-with-suspected-drug-induced-liver-injury-dili-as-biomarkers-of-recovery
#17
Valentina Peta, Chantal Tse, Hugo Perazzo, Mona Munteanu, Yen Ngo, An Ngo, Nittia Ramanujam, Lea Verglas, Maxime Mallet, Vlad Ratziu, Dominique Thabut, Marika Rudler, Vincent Thibault, Ina Schuppe-Koistinen, Dominique Bonnefont-Rousselot, Bernard Hainque, Françoise Imbert-Bismut, Michael Merz, Gerd Kullak-Ublick, Raul Andrade, Florian van Boemmel, Eckart Schott, Thierry Poynard
BACKGROUND: There is a clear need for better biomarkers of drug-induced-liver-injury (DILI). AIMS: We aimed to evaluate the possible prognostic value of ActiTest and FibroTest proteins apoliprotein-A1, haptoglobin and alpha-2-macroglobulin, in patients with DILI. METHODS: We analyzed cases and controls included in the IMI-SAFE-T-DILI European project, from which serum samples had been stored in a dedicated biobank. The analyses of ActiTest and FibroTest had been prospectively scheduled...
2017: PloS One
https://www.readbyqxmd.com/read/29258884/drug-toxicity-profiling-of-a-saccharomyces-cerevisiae-deubiquitinase-deletion-panel-shows-that-acetaminophen-mimics-tyrosine
#18
Angelina Huseinovic, Marc van Dijk, Nico P E Vermeulen, Fred van Leeuwen, Jan M Kooter, J Chris Vos
Post-translational protein modification by addition or removal of the small polypeptide ubiquitin is involved in a range of critical cellular processes, like proteasomal protein degradation, DNA repair, gene expression, internalization of membrane proteins, and drug sensitivity. We recently identified genes important for acetaminophen (APAP) toxicity in a comprehensive screen and our findings suggested that a small set of yeast strains carrying deletions of ubiquitin-related genes can be informative for drug toxicity profiling...
December 16, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29243082/dihydroquercetin-ameliorated-acetaminophen-induced-hepatic-cytotoxicity-via-activating-jak2-stat3-pathway-and-autophagy
#19
Wenjing Zai, Wei Chen, Jingyun Luan, Jiajun Fan, Xuyao Zhang, Zimei Wu, Tao Ding, Dianwen Ju, Hongrui Liu
Acetaminophen (APAP) overdose is currently the leading cause of acute liver disease, but therapeutic treatment strategies are commonly limited. Although dihydroquercetin (DHQ) is an attractive botanical antioxidant, its protective potential for liver disease remains elusive. The present study investigated the protective effects of DHQ against APAP-induced hepatic cytotoxicity. Primary mouse hepatocytes were treated with different concentrations of DHQ followed by APAP administration. Our data showed that DHQ relieved APAP-induced growth inhibition and lactate dehydrogenase (LDH) release in a dose-dependent manner, as well as inhibited APAP-induced necrosis and extracellular signal regulated kinase-c-Jun-N-terminal kinase (ERK-JNK) stress...
December 14, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29233977/the-mitochondrial-negative-regulator-mcj-is-a-therapeutic-target-for-acetaminophen-induced-liver-injury
#20
Lucía Barbier-Torres, Paula Iruzubieta, David Fernández-Ramos, Teresa C Delgado, Daniel Taibo, Virginia Guitiérrez-de-Juan, Marta Varela-Rey, Mikel Azkargorta, Nicolas Navasa, Pablo Fernández-Tussy, Imanol Zubiete-Franco, Jorge Simon, Fernando Lopitz-Otsoa, Sofia Lachiondo-Ortega, Javier Crespo, Steven Masson, Misti Vanette McCain, Erica Villa, Helen Reeves, Felix Elortza, Maria Isabel Lucena, Maria Isabel Hernández-Alvarez, Antonio Zorzano, Raúl J Andrade, Shelly C Lu, José M Mato, Juan Anguita, Mercedes Rincón, María Luz Martínez-Chantar
Acetaminophen (APAP) is the active component of many medications used to treat pain and fever worldwide. Its overuse provokes liver injury and it is the second most common cause of liver failure. Mitochondrial dysfunction contributes to APAP-induced liver injury but the mechanism by which APAP causes hepatocyte toxicity is not completely understood. Therefore, we lack efficient therapeutic strategies to treat this pathology. Here we show that APAP interferes with the formation of mitochondrial respiratory supercomplexes via the mitochondrial negative regulator MCJ, and leads to decreased production of ATP and increased generation of ROS...
December 12, 2017: Nature Communications
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