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acetaminophen and liver

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https://www.readbyqxmd.com/read/29342206/silymarin-prevents-acetaminophen-induced-hepatotoxicity-in-mice
#1
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/29338970/baicalein-and-baicalin-alleviate-acetaminophen-induced-liver-injury-by-activating-nrf2-antioxidative-pathway-the-involvement-of-erk1-2-and-pkc
#2
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/29331651/activation-of-p62-keap1-nrf2-antioxidant-pathway-in-the-early-stage-of-acetaminophen-induced-acute-liver-injury-in-mice
#3
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/29331340/hsp72-protects-from-liver-injury-via-attenuation-of-hepatocellular-death-oxidative-stress-and-jnk-signaling
#4
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/29325178/modulation-of-o-glcnac-levels-in-the-liver-impacts-acetaminophen-induced-liver-injury-by-affecting-protein-adduct-formation-and-glutathione-synthesis
#5
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/29318967/inter-individual-variability-in-activity-of-the-major-drug-metabolizing-enzymes-in-liver-homogenates-of-20-individuals
#6
J Chris Vos, Shalenie P den Braver-Sewradj, Michiel W den Braver, Marc van Dijk, Yongjie Zhang, Stefan J Dekker, Lukas Wijaya, Nico P E Vermeulen, Lysiane Richert, Jan N M Commandeur
BACKGROUND: Inter-individual variability in hepatic drug metabolizing enzyme (DME) activity is a major contributor to heterogeneity in drug clearance and safety. Accurate data on expression levels and activities of DMEs is an important prerequisite for in vitro-in vivo extrapolation and in silico based predictions. Characterization and assessment of inter-correlations of the major DMEs cytochrome P450s (CYPs) and UDP-glucuronosyltransferases (UGTs) have been extensively documented, but simultaneous quantification including other major DMEs has been lacking...
January 8, 2018: Current Drug Metabolism
https://www.readbyqxmd.com/read/29317122/directly-injected-native-bone-marrow-stem-cells-cannot-incorporate-into-acetaminophen-induced-liver-injury
#7
Azadeh Babaei, Azam Katoonizadeh, Azam Ranjbar, Mahmood Naderi, Naser Ahmadbeigi
The paucity of liver donation highlights the use of cell-based strategies for end-stage liver failure. We recently showed that bone marrow-derived aggregates (BMDAs) can completely restore the hematopoietic system in gamma-irradiated mice. These aggregates are stem and progenitor cells in the bone marrow (BM), composed of both hematopoietic and non-hematopoietic lineages. Furthermore, reports showed that resident BM cells migrate to the liver and integrate themselves into the tissue in small numbers. Hence, we hypothesized that direct delivery of BMDAs to the damaged liver might enhance the integration of BM cells in the liver because of its stemness property, intact BM architecture, the physical proximity of these niche-like structures to the damaged sites and the existence of liver paracrine factors...
January 6, 2018: Biologicals: Journal of the International Association of Biological Standardization
https://www.readbyqxmd.com/read/29301418/hypoglycemia-and-lactic-acidosis-outperform-king-s-college-criteria-for-predicting-death-or-transplant-in-acetaminophen-toxic-patients
#8
Michael Levine, Samuel J Stellpflug, Anthony F Pizon, David A Peak, Janna Villano, Timothy Wiegand, Christian Dib, Stephen H Thomas
IMPORTANCE: Acetaminophen toxicity is common and is characterized by hepatic failure. In cases that are not improving with standard medical therapy with N-acetylcysteine, some patients may require hepatic transplant. While there are various criteria to predict patients who might benefit from transplant, the King's College criteria remain one of the most widely used. However, the King's College criteria have several limitations and do not incorporate glucose, an important marker of hepatic function...
January 5, 2018: Clinical Toxicology
https://www.readbyqxmd.com/read/29281794/reduction-and-scavenging-of-chemically-reactive-drug-metabolites-by-nad-p-h-quinone-oxidoreductase-1-and-nrh-quinone-oxidoreductase-2-and-variability-in-hepatic-concentrations
#9
Shalenie P den Braver-Sewradj, Michiel W den Braver, Robin M Toorneman, Stephanie van Leeuwen, Yongjie Zhang, Stefan J Dekker, Nico P E Vermeulen, Jan N M Commandeur, J Chris Vos
Detoxicating enzymes NAD(P)H:quinone oxidoreductase 1 (NQO1) and NRH:quinone oxidoreductase 2 (NQO2) catalyze the two-electron reduction of quinone-like compounds. The protective role of the polymorphic NQO1 and NQO2 enzymes is especially of interest in the liver as the major site of drug bioactivation to chemically reactive drug metabolites. In the current study, we quantified the concentrations of NQO1 and NQO2 in 20 human liver donors and NQO1 and NQO2 activities with quinone-like drug metabolites. Hepatic NQO1 concentrations ranged from 8 to 213 nM...
December 27, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/29274831/preoperative-cesarean-section-intravenous-acetaminophen-treatment-for-postoperative-pain-control-a-randomized-double-blinded-placebo-control-trial
#10
Craig V Towers, Sarah Shelton, Jaclyn van Nes, Emily Gregory, Emily Liske, Arion Smalley, Edward Mobley, Barbara Faircloth, Kim B Fortner
BACKGROUND: The United States currently has an opioid use disorder epidemic and research evaluating ways to minimize the use of opioids post-surgery are needed. One of these options is intravenous (IV) acetaminophen. If the use of preoperative IV acetaminophen was found to be effective for cesarean delivery, this would be beneficial for both the mother and breastfeeding neonate. OBJECTIVE: The primary study objective was to see if maternal opioid use was significantly less in the postoperative period for the study group that received 1 gram of IV acetaminophen preoperatively compared with a control group that received placebo...
December 21, 2017: American Journal of Obstetrics and Gynecology
https://www.readbyqxmd.com/read/29246445/protective-effect-of-genetic-deletion-of-pannexin1-in-experimental-mouse-models-of-acute-and-chronic-liver-disease
#11
Joost Willebrords, Michaël Maes, Isabel Veloso Alves Pereira, Tereza Cristina da Silva, Veronica Mollica Govoni, Valéria Veras Lopes, Sara Crespo Yanguas, Valery I Shestopalov, Marina Sayuri Nogueira, Inar Alves de Castro, Anwar Farhood, Inge Mannaerts, Leo van Grunsven, Jephte Akakpo, Margitta Lebofsky, Hartmut Jaeschke, Bruno Cogliati, Mathieu Vinken
Pannexins are transmembrane proteins that form communication channels connecting the cytosol of an individual cell with its extracellular environment. A number of studies have documented the presence of pannexin1 in liver as well as its involvement in inflammatory responses. In this study, it was investigated whether pannexin1 plays a role in acute liver failure and non-alcoholic steatohepatitis, being prototypical acute and chronic liver pathologies, respectively, both featured by liver damage, oxidative stress and inflammation...
December 12, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29243082/dihydroquercetin-ameliorated-acetaminophen-induced-hepatic-cytotoxicity-via-activating-jak2-stat3-pathway-and-autophagy
#12
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/29235390/mir-122-and-other-micrornas-as-potential-circulating-biomarkers-of-drug-induced-liver-injury
#13
Lawrence S Howell, Lucy Ireland, B Kevin Park, Christopher E Goldring
Drug-induced liver injury (DILI) is a severe adverse drug reaction which is of major concern to patients, clinicians and the pharmaceutical industry. Accurate and rapid detection of DILI is important for patient stratification and treatment in the clinic and benefits preclinical drug design and risk assessment. MicroRNAs (miRNAs) offer a potential new and improved class of circulating biomarkers of DILI over the current gold standard biomarkers. Areas covered: This review highlights the shortcomings of the currently used panel of biomarkers and how miRNAs, primarily miR-122, show an improved level of specificity and sensitivity in the prediction of DILI...
December 15, 2017: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/29233977/the-mitochondrial-negative-regulator-mcj-is-a-therapeutic-target-for-acetaminophen-induced-liver-injury
#14
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
https://www.readbyqxmd.com/read/29231843/the-lipid-lowering-and-cardioprotective-effects-of-vernonia-calvoana-ethanol-extract-in-acetaminophen-treated-rats
#15
Godwin Eneji Egbung, Item Justin Atangwho, Ochuole Diana Odey, Victor Ndubuisi Ndiodimma
Background: Paracetamol overdose/abuse as a result of self-medication is a common occurrence amongst people living in low/middle income countries. The present study was designed to investigate the hypolipidemic and cardioprotective potentials of Vernonia calvoana (VC) ethanol extract in acetaminophen (paracetamol)-treated rats. Methods: Thirty-five Wistar rats weighing 100-150 g were randomly assigned into five groups of seven rats each. Groups 2-5 received high doses of paracetamol to induce liver damage, while group 1 was used as normal control...
December 12, 2017: Medicines (Basel, Switzerland)
https://www.readbyqxmd.com/read/29222960/drug-induced-acute-liver-failure-in-children-and-adults-results-of-a-single-center-study-of-128-patients
#16
Harshad Devarbhavi, Mallikarjun Patil, Vishnu Vardhan Reddy, Rajvir Singh, Tarun Joseph, Deepak Ganga
BACKGROUND AND AIMS: Drugs producing acute liver failure (ALF) are uncommon and vary geographically. Here we review the implicated drugs, clinical features, laboratory characteristics and outcome of patients with drug-induced ALF (DIALF). We analyzed the predictors of mortality and their relationship with MELD, Kings College criteria (KCC) and ALFSG prognostic index. METHODS: We identified DIALF patients from our drug-induced liver injury (DILI) registry (1997-2017)...
December 9, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/29217823/lysophosphatidic-acid-protects-against-acetaminophen-induced-acute-liver-injury
#17
Geon Ho Bae, Sung Kyun Lee, Hyung Sik Kim, Mingyu Lee, Ha Young Lee, Yoe-Sik Bae
We investigated the effect of lysophosphatidic acid (LPA) in experimental acetaminophen (APAP)-induced acute liver injury. LPA administration significantly reduced APAP-challenged acute liver injury, showing attenuated liver damage, liver cell death and aspartate aminotransferase and alanine aminotransferase levels. APAP overdose-induced mortality was also significantly decreased by LPA administration. Regarding the mechanism involved in LPA-induced protection against acute liver injury, LPA administration significantly increased the glutathione level, which was markedly decreased in APAP challenge-induced acute liver injury...
December 8, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29206839/development-of-an-organ-failure-score-in-acute-liver-failure-for-transplant-selection-and-identification-of-patients-at-high-risk-of-futility
#18
Francesco Figorilli, Antonella Putignano, Olivier Roux, Pauline Houssel-Debry, Claire Francoz, Catherine Paugam-Burtz, Olivier Soubrane, Banwari Agarwal, François Durand, Rajiv Jalan
INTRODUCTION: King's College Hospital criteria are currently used to select liver transplant candidates in acetaminophen-related acute liver failure (ALF). Although widely accepted, they show a poor sensitivity in predicting pre-transplant mortality and cannot predict the outcome after surgery. In this study we aimed to develop a new prognostic score that can allow patient selection for liver transplantation more appropriately and identify patients at high risk of futile transplantation...
2017: PloS One
https://www.readbyqxmd.com/read/29203962/sake-lees-hydrolysate-protects-against-acetaminophen-induced-hepatotoxicity-via-activation-of-the-nrf2-antioxidant-pathway
#19
Kayoko Kawakami, Chie Moritani, Misugi Uraji, Akiko Fujita, Koji Kawakami, Tadashi Hatanaka, Etsuko Suzaki, Seiji Tsuboi
Acetaminophen is a commonly used analgesic. However, an overdose of acetaminophen causes severe hepatotoxicity via depletion of hepatic glutathione. Here, we investigated the protective effects of sake lees hydrolysate against acetaminophen-induced hepatotoxicity in mice. Sake lees hydrolysate was administered orally to ICR mice for seven days. Six hours after acetaminophen treatment, the mice were sacrificed, and blood and liver samples were collected for analysis. Treatment with acetaminophen markedly increased the levels of serum alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, and alkaline phosphatase...
November 2017: Journal of Clinical Biochemistry and Nutrition
https://www.readbyqxmd.com/read/29199145/acetaminophen-induced-acute-liver-failure-is-more-common-and-more-severe-in-women
#20
Jessica B Rubin, Bilal Hameed, Michelle Gottfried, William M Lee, Monika Sarkar
BACKGROUND & AIMS: Acetaminophen overdose is the leading cause of acute liver injury (ALI) and acute liver failure (ALF) in the developed world. Sex differences in acetaminophen-induced hepatotoxicity have not been described. METHODS: We collected data from the Acute Liver Failure Study Group cohort, a national registry of 32 academic medical centers in North America of adults with ALI or ALF, including 1162 patients with acetaminophen-induced ALI (n=250) or acetaminophen-induced ALF (n=912) from January 2000 through September 2016...
November 30, 2017: Clinical Gastroenterology and Hepatology
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