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acetaminophen and liver

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https://www.readbyqxmd.com/read/29136249/natural-polyphenol-chlorogenic-acid-protects-against-acetaminophen-induced-hepatotoxicity-by-activating-erk-nrf2-antioxidative-pathway
#1
Mengjuan Wei, Zhiyong Zheng, Liang Shi, Yao Jin, Lili Ji
Hepatotoxicity due to acetaminophen (APAP) overdose is a leading cause of drug-induced acute liver failure in clinic. Chlorogenic acid (CGA), a dietary polyphenol, was reported to prevent APAP-induced liver injury in our previous studies. This study aims to investigate the protection provided by CGA against APAP-induced hepatotoxicity via focusing on nuclear factor erythroid 2-related factor 2 (Nrf2) and extracellular regulated protein kinases (ERK)1/2. CGA prevented APAP-induced oxidative liver injury and enhanced Nrf2 activation in mice and in hepatocytes in vitro...
November 10, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29109520/a-perfusion-incubator-liver-chip-for-3d-cell-culture-with-application-on-chronic-hepatotoxicity-testing
#2
Fang Yu, Rensheng Deng, Wen Hao Tong, Li Huan, Ng Chan Way, Anik IslamBadhan, Ciprian Iliescu, Hanry Yu
Liver chips have been developed to recapitulate in vivo physiological conditions to enhance hepatocyte functions for assessing acute responses to drugs. To develop liver chips that can assess repeated dosing chronic hepatotoxicity, we need to ensure that hepatocyte functions be maintained at constant values over two weeks in stable culture conditions of sterility, temperature, pH, fluidic-flow of culture media and drugs. We have designed a perfusion-incubator-liver-chip (PIC) for 3D cell culture, that assures a tangential flow of the media over the spheroids culture...
November 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29109123/a-protective-function-of-il-22bp-in-ischemia-reperfusion-and-acetaminophen-induced-liver-injury
#3
Dörte Kleinschmidt, Anastasios D Giannou, Heather M McGee, Jan Kempski, Babett Steglich, Francis Jessica Huber, Thomas Michael Ernst, Ahmad Mustafa Shiri, Claudia Wegscheid, Elena Tasika, Peter Hübener, Philipp Huber, Tanja Bedke, Niklas Steffens, Theodora Agalioti, Tobias Fuchs, Jill Noll, Hannelore Lotter, Gisa Tiegs, Ansgar W Lohse, Jonathan H Axelrod, Eithan Galun, Richard A Flavell, Nicola Gagliani, Samuel Huber
Acute liver injury can be secondary to a variety of causes, including infections, intoxication, and ischemia. All of these insults induce hepatocyte death and subsequent inflammation, which can make acute liver injury a life-threatening event. IL-22 is a dual natured cytokine which has context-dependent protective and pathogenic properties during tissue damage. Accordingly, IL-22 was shown to promote liver regeneration upon acute liver damage. However, other studies suggest pathogenic properties of IL-22 during chronic liver injury...
November 6, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29107792/caffeine-and-acetaminophen-association-effects-on-mitochondrial-bioenergetics
#4
Débora F Gonçalves, Nelson R de Carvalho, Martim B Leite, Aline A Courtes, Diane D Hartmann, Sílvio T Stefanello, Ingrid K da Silva, Jéferson L Franco, Félix A A Soares, Cristiane L Dalla Corte
AIMS: Many studies have been demonstrating the role of mitochondrial function in acetaminophen (APAP) hepatotoxicity. Since APAP is commonly consumed with caffeine, this work evaluated the effects of the combination of APAP and caffeine on hepatic mitochondrial bioenergetic function in mice. MAIN METHODS: Mice were treated with caffeine (20mg/kg, intraperitoneal (i.p.)) or its vehicle and, after 30min, APAP (250mg/kg, i.p.) or its vehicle. Four hours later, livers were removed, and the parameters associated with mitochondrial function and oxidative stress were evaluated...
October 28, 2017: Life Sciences
https://www.readbyqxmd.com/read/29091898/protective-effect-of-dioscin-against-thioacetamide-induced-acute-liver-injury-via-fxr-ampk-signaling-pathway-in-vivo
#5
Lingli Zheng, Lianhong Yin, Lina Xu, Yan Qi, Hua Li, Youwei Xu, Xu Han, Kexin Liu, Jinyong Peng
Our previous works showed that dioscin, a natural product, could protect liver from acute liver damages induced by dimethylnitrosamine, ethanol, carbon tetrachloride and acetaminophen. However, the effect of dioscin on thioacetamide (TAA)-induced acute liver injury still remained unknown. The purpose of this study was to investigate whether dioscin confers a protective effect against TAA-induced acute liver injury in rats and mice. The results showed that dioscin decreased the serum levels of ALT, AST, and rehabilitated histopathological changes compared with the model groups...
October 28, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29088996/aggressive-treatment-of-life-threatening-hypophosphatemia-during-recovery-from-fulminant-hepatic-failure-a-case-report
#6
Brittany D Bissell, Jason E Davis, Alexander H Flannery, David A Adkins, Melissa L Thompson Bastin
Acute liver failure secondary to acetaminophen overdose can be a life-threatening condition, characterized by severe electrolyte derangements. Hepatocyte regeneration is associated with phosphorous utilization and is a known complication of liver recovery following injury. We report the case of profound, life-threatening hypophosphatemia following recovery from acute fulminant liver failure. As the liver enzymes normalized, serum phosphorous levels plummeted. Our patient required an aggressive, individualized phosphorus replacement regimen, which resulted in a continuous infusion of intravenous (IV) sodium phosphate, titrated to a maximum rate of 30 mmol/h or 0...
January 1, 2017: Journal of Intensive Care Medicine
https://www.readbyqxmd.com/read/29079404/knowledge-of-appropriate-acetaminophen-use-a-survey-of-college-age-women
#7
Janice L Stumpf, Allison C Liao, Stacy Nguyen, Amy J Skyles, Cesar Alaniz
OBJECTIVES: To evaluate college-age women's knowledge of appropriate doses and potential toxicities of acetaminophen, competency in interpreting Drug Facts label dosing information, and ability to recognize products containing acetaminophen. METHODS: In this cross-sectional prospective study, a 20-item written survey was provided to female college students at a University of Michigan fundraising event in March 2015. RESULTS: A total of 203 female college students, 18-24 years of age, participated in the study...
October 24, 2017: Journal of the American Pharmacists Association: JAPhA
https://www.readbyqxmd.com/read/29067470/multiple-micrornas-function-as-self-protective-modules-in-acetaminophen-induced-hepatotoxicity-in-humans
#8
Dianke Yu, Leihong Wu, Pritmohinder Gill, William H Tolleson, Si Chen, Jinchun Sun, Bridgett Knox, Yaqiong Jin, Wenming Xiao, Huixiao Hong, Yong Wang, Zhen Ren, Lei Guo, Nan Mei, Yongli Guo, Xi Yang, Leming Shi, Yinting Chen, Linjuan Zeng, Kostiantyn Dreval, Volodymyr Tryndyak, Igor Pogribny, Hong Fang, Tieliu Shi, Sandra McCullough, Sudeepa Bhattacharyya, Laura Schnackenberg, William Mattes, Richard D Beger, Laura James, Weida Tong, Baitang Ning
Acetaminophen (APAP) overdose is the leading cause of acute liver failure. Yet the mechanisms underlying adaptive tolerance toward APAP-induced liver injury are not fully understood. To better understand molecular mechanisms contributing to adaptive tolerance to APAP is an underpinning foundation for APAP-related precision medicine. In the current study, the mRNA and microRNA (miRNA) expression profiles derived from next generation sequencing data for APAP-treated (5 and 10 mM) HepaRG cells and controls were analyzed systematically...
October 24, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/29056914/acetaminophen-induced-liver-injury-alters-the-acyl-ethanolamine-based-anti-inflammatory-signaling-system-in-liver
#9
Patricia Rivera, Antoni Pastor, Sergio Arrabal, Juan Decara, Antonio Vargas, Laura Sánchez-Marín, Francisco J Pavón, Antonia Serrano, Dolores Bautista, Anna Boronat, Rafael de la Torre, Elena Baixeras, M Isabel Lucena, Fernando R de Fonseca, Juan Suárez
Protective mechanisms against drug-induced liver injury are actively being searched to identify new therapeutic targets. Among them, the anti-inflammatory N-acyl ethanolamide (NAE)-peroxisome proliferators activated receptor alpha (PPARα) system has gained much interest after the identification of its protective role in steatohepatitis and liver fibrosis. An overdose of paracetamol (APAP), a commonly used analgesic/antipyretic drug, causes hepatotoxicity, and it is being used as a liver model. In the present study, we have analyzed the impact of APAP on the liver NAE-PPARα system...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29054140/acetaminophen-toxicity-novel-insights-into-mechanisms-and-future-perspectives
#10
Anup Ramachandran, Hartmut Jaeschke
Acetaminophen (APAP) overdose is the most common cause of acute liver failure in the United States and decades of intense study of its pathogenesis resulted in development of the antidote Nacetylcysteine, which facilitates scavenging of the reactive metabolite and is the only treatment in clinical use. However, the narrow therapeutic window of this intervention necessitates a better understanding of the intricacies of APAP-induced liver injury for development of additional therapeutic approaches which can benefit late presenting patients...
October 20, 2017: Gene Expression
https://www.readbyqxmd.com/read/29053632/protective-effect-of-flavonoids-from-ziziphus-jujuba-cv-jinsixiaozao-against-acetaminophen-induced-liver-injury-by-inhibiting-oxidative-stress-and-inflammation-in-mice
#11
Weizhen Huang, Yongjie Wang, Xiaoyan Jiang, Yueyue Sun, Zhongxi Zhao, Siying Li
This study was aimed to investigate the chemical composition, antioxidant activities and hepatoprotective effect of flavonoids from Ziziphus jujuba cv. Jinsixiaozao (ZJF). The composition of ZJF was analyzed by high performance liquid chromatography (HPLC) and Liquid chromatography-mass spectrometry (LC-MS), and antioxidant properties were investigated by biological assays in vitro. The hepatoprotective activity of ZJF was evaluated in acetaminophen (APAP)-treated BALB/c mice. Results indicate that ZJF displayed significant antioxidant capacity...
October 20, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29050482/the-effect-of-sulforaphane-on-oxidative-stress-and-inflammation-in-rats-with-toxic-hepatitis-induced-by-acetaminophene
#12
E Dokumacioglu, H Iskender, M S Aktas, B Hanedan, A Dokumacioglu, T M Sen, A Musmul
OBJECTIVE: The aim of the present study was to reveal the possible effect of sulforaphane on oxidative stress and inflammation in rats liver with toxic hepatitis induced by acetaminophene. BACKGROUND: Sulforaphane is a compound with high antioxidant properties. Acetaminophen, which is a para-aminophenol derivative, can lead to fatal hepatic necrosis with direct hepatotoxic effects at high doses. METHODS: Thirty six male Sprague-Dawley rats were randomly divided into four groups...
2017: Bratislavské Lekárske Listy
https://www.readbyqxmd.com/read/29038465/nmi-and-ifp35-serve-as-proinflammatory-damps-during-cellular-infection-and-injury
#13
Zhikai Xiahou, Xiangli Wang, Juan Shen, Xiaoxiao Zhu, Feng Xu, Rong Hu, Deyin Guo, Henan Li, Yong Tian, Yingfang Liu, Huanhuan Liang
Damage-associated molecular patterns (DAMP) trigger innate immune response and exacerbate inflammation to combat infection and cellular damage. Identifying DAMPs and revealing their functions are thus of crucial importance. Here we report that two molecules, N-myc and STAT interactor (NMI) and interferon-induced protein 35 (IFP35) act as DAMPs and are released by activated macrophages during lipopolysaccharide-induced septic shock or acetaminophen-induced liver injury. We show that extracellular NMI and IFP35 activate macrophages to release proinflammatory cytokines by activating nuclear factor-κB through the Toll-like receptor 4 pathway...
October 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/29035890/biocharacterization-of-heat-shock-protein-90-in-acetaminophen-treated-livers-without-conspicuous-drug-induced-liver-injury
#14
Ka Wu, Chao Guo, Min Su, Xinmou Wu, Rong Li
BACKGROUND/AIMS: Acetaminophen (APAP) refers to a medication used to manage pain and fever symptoms. Heat shock protein 90 (Hsp90) is to be expressed during various stresses, such as wound healing and tissue remodeling. Recently, it is discovered that Hsp90 is a potential modifier of cytogenesis. In comparison to clinical references of liver damage, this study was designed to assess the potential bioeffect of Hsp90 in APAP-treated livers without conspicuous drug induced liver injury (DILI)...
October 16, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29032512/il-33-signalling-in-liver-immune-cells-enhances-drug-induced-liver-injury-and-inflammation
#15
Maísa Mota Antunes, Alan Moreira Araújo, Ariane Barros Diniz, Rafaela Vaz Sousa Pereira, Débora Moreira Alvarenga, Bruna Araújo David, Renata Monti Rocha, Maria Alice Freitas Lopes, Sarah Cozzer Marchesi, Brenda Naemi Nakagaki, Érika Carvalho, Pedro Elias Marques, Bernhard Ryffel, Valérie Quesniaux, Rodrigo Guabiraba Brito, José Carlos Alves Filho, Denise Carmona Cara, Rafael Machado Rezende, Gustavo Batista Menezes
OBJECTIVE AND DESIGN: The aim of this study was to investigate the contribution of IL-33/ST2 axis in the onset and progression of acute liver injury using a mice model of drug-induced liver injury (DILI). MATERIAL AND TREATMENTS: DILI was induced by overdose administration of acetaminophen (APAP) by oral gavage in wild-type BALB/c, ST2-deficient mice and in different bone marrow chimeras. Neutrophils were depleted by anti-Ly6G and macrophages with clodronate liposomes (CLL)...
October 14, 2017: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/29022574/osthole-prevents-acetaminophen-induced-liver-injury-in-mice
#16
Yun Cai, Wu Sun, Xin-Xin Zhang, Yan-Die Lin, Hao Chen, Hao Li
Acetaminophen (APAP) overdose leads to severe hepatotoxicity. Osthole, a natural coumarin found in traditional Chinese medicinal herbs, has therapeutic potential in the treatment of various diseases. In this study, we investigated the effects of osthole against APAP-induced hepatotoxicity in mice. Mice were administered osthole (100 mg·kg(-1)·d(-1), ip) for 3 d, then on the fourth day APAP (300 mg/kg, ip) was co-administered with osthole. The mice were euthanized post-APAP, their serum and livers were collected for analysis...
October 12, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28987363/extract-from-mulberry-morus-australis-leaf-decelerate-acetaminophen-induced-hepatic-inflammation-involving-downregulation-of-myeloid-differentiation-factor-88-myd88-signals
#17
Chi-Ting Horng, Zhi-Hong Liu, Yu-Ting Huang, Huei-Jane Lee, Chau-Jong Wang
Acetaminophen (APAP) induced inflammation and oxidative stress can cause cell death to induce liver damage. The antioxidative and anti-inflammatory effect of Mulberry (Morus australis) leaf extract (MLE) was shown in previous studies. In this study, we investigated the modulation of MLE on APAP induced inflammation and oxidative stress in rat liver injury or liver cancer cell (HepG2). Wistar rat was fed orally with MLE (0.5% or 1.0 %) for 1 week, and then, 900 mg/kg of APAP was injected intraperitoneally (i...
October 2017: Journal of Food and Drug Analysis
https://www.readbyqxmd.com/read/28986131/selenoprotein-msrb1-deficiency-exacerbates-acetaminophen-induced-hepatotoxicity-via-increased-oxidative-damage
#18
Ki Young Kim, Geun-Hee Kwak, Mahendra Pratap Singh, Vadim N Gladyshev, Hwa-Young Kim
Acetaminophen (APAP) overdose induces acute liver damage and failure via reactive oxygen species production and glutathione (GSH) depletion. Methionine sulfoxide reductase B1 (MsrB1) is an antioxidant selenoenzyme that specifically catalyzes the reduction of methionine R-sulfoxide residues. In this study, we used MsrB1 gene-knockout mice and primary hepatocytes to investigate the effect of MsrB1 on APAP-induced hepatotoxicity. Analyses of histological alterations and serum indicators of liver damage showed that MsrB1(-/-) mice were more susceptible to APAP-induced acute liver injury than wild-type (MsrB1(+/+)) mice...
October 3, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28984147/celastrol-ameliorates-acetaminophen-induced-oxidative-stress-and-cytotoxicity-in-hepg2-cells
#19
A T Jannuzzi, M Kara, B Alpertunga
Acetaminophen (APAP) is the most commonly used analgesic and antipyretic drug in the world. However, hepatotoxicity caused by APAP overdose is the most frequent cause of acute liver failure worldwide and oxidative stress involved in the pathogenesis of APAP hepatotoxicity. Celastrol is a natural triterpenoid derived from Tripterygium wilfordii Hook F. that exhibits antioxidant, anti-inflammatory, and antitumor activities. In this study, we aimed to investigate the potential ameliorative effects of celastrol against APAP-induced cytotoxicity and oxidative stress...
January 1, 2017: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/28983815/the-association-between-fabp7-serum-levels-with-survival-and-neurological-complications-in-acetaminophen-induced-acute-liver-failure-a-nested-case-control-study
#20
Constantine J Karvellas, Jaime L Speiser, Mélanie Tremblay, William M Lee, Christopher F Rose
BACKGROUND: Acetaminophen (APAP)-induced acute liver failure (ALF) is associated with significant mortality due to intracranial hypertension (ICH), a result of cerebral edema (CE) and astrocyte swelling. Brain-type fatty acid-binding protein (FABP7) is a small (15 kDa) cytoplasmic protein abundantly expressed in astrocytes. The aim of this study was to determine whether serum FABP7 levels early (day 1) or late (days 3-5) level were associated with 21-day mortality and/or the presence of ICH/CE in APAP-ALF patients...
October 5, 2017: Annals of Intensive Care
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