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https://www.readbyqxmd.com/read/28442342/methionine-sulfoxide-reductase-a-protects-hepatocytes-against-acetaminophen-induced-toxicity-via-regulation-of-thioredoxin-reductase-1-expression
#1
Mahendra Pratap Singh, Geun-Hee Kwak, Ki Young Kim, Hwa-Young Kim
Thioredoxin reductase 1 (TXNRD1) is associated with susceptibility to acetaminophen (APAP)-induced liver damage. Methionine sulfoxide reductase A (MsrA) is an antioxidant and protein repair enzyme that specifically catalyzes the reduction of methionine S-sulfoxide residues. We have previously shown that MsrA deficiency exacerbates acute liver injury induced by APAP. In this study, we used primary hepatocytes to investigate the underlying mechanism of the protective effect of MsrA against APAP-induced hepatotoxicity...
April 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28440304/the-natural-history-of-severe-acute-liver-injury
#2
David G Koch, J L Speiser, V Durkalski, R J Fontana, T Davern, B McGuire, R T Stravitz, A M Larson, I Liou, O Fix, M L Schilsky, T McCashland, J E Hay, N Murray, O S Shaikh, D Ganger, A Zaman, S B Han, R T Chung, R S Brown, S Munoz, K R Reddy, L Rossaro, R Satyanarayana, A J Hanje, J Olson, R M Subramanian, C Karvellas, B Hameed, A H Sherker, W M Lee, A Reuben
OBJECTIVES: Acute liver failure (ALF) is classically defined by coagulopathy and hepatic encephalopathy (HE); however, acute liver injury (ALI), i.e., severe acute hepatocyte necrosis without HE, has not been carefully defined nor studied. Our aim is to describe the clinical course of specifically defined ALI, including the risk and clinical predictors of poor outcomes, namely progression to ALF, the need for liver transplantation (LT) and death. METHODS: 386 subjects prospectively enrolled in the Acute Liver Failure Study Group registry between 1 September 2008 through 25 October 2013, met criteria for ALI: International Normalized Ratio (INR)≥2...
April 25, 2017: American Journal of Gastroenterology
https://www.readbyqxmd.com/read/28435131/repression-of-acetaminophen-induced-hepatotoxicity-by-a-combination-of-celastrol-and-brilliant-blue-g
#3
Heba A Abdelaziz, Mohamed E Shaker, Mohamed F Hamed, Nariman M Gameil
The sterile inflammatory response is an eminent contributor to acetaminophen (APAP)-hepatotoxicity in humans. Recent advances unraveled an axial role of the NLRP3-inflammasome in APAP-post injury inflammation. Nevertheless, the role of signaling events preceded the NLRP3-inflammasome activation, like the transcription factor NF-κB and the purinergic receptor P2×7, is still unclear and needs further elucidation. Here, we investigated the pharmacological inhibition of these upstream signaling molecules by celastrol and brilliant blue G (BBG) (separately or simultaneously) in APAP-hepatotoxicity in mice...
April 20, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28430162/ameliorative-effects-and-possible-molecular-mechanism-of-action-of-black-ginseng-panax-ginseng-on-acetaminophen-mediated-liver-injury
#4
Jun-Nan Hu, Zhi Liu, Zi Wang, Xin-Dian Li, Lian-Xue Zhang, Wei Li, Ying-Ping Wang
Background: Frequent overdosing of acetaminophen (APAP) has become the major cause of acute liver injury (ALI). The present study aimed to evaluate the potential hepatoprotective effects of black ginseng (BG) on APAP-induced mice liver injuries and the underlying mechanisms of action were further investigated for the first time. Methods: Mice were treated with BG (300, 600 mg/kg) by oral gavage once a day for seven days. On the 7th day, all mice were treated with 250 mg/kg APAP which caused severe liver injury after 24 h and hepatotoxicity was assessed...
April 21, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28429935/saponins-ginsenosides-from-the-leaves-of-panax-quinquefolius-ameliorated-acetaminophen-induced-hepatotoxicity-in-mice
#5
Xing-Yue Xu, Jun-Nan Hu, Zhi Liu, Rui Zhang, Yu-Fang He, Wei Hou, Zhi-Qing Wang, Ge Yang, Wei Li
Acetaminophen (APAP) overdose is one of the most common inducements of drug-induced liver injury (DILI) in the world. The main purpose of this paper was to investigate the liver protection activity of saponins (ginsenosides) from the leaves of Panax quinquefolius (PQS) against APAP-induced hepatotoxicity, and the involved mechanisms were demonstrated for the first time. Mice were pretreated with PQS (150 and 300 mg/kg) by oral gavage for 7 days before being treated with 250 mg/kg APAP. Severe liver injury was exerted at 24 h post-APAP, and hepatotoxicity was assessed...
April 25, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28428777/lactobacillus-fermentum-postbiotic-induced-autophagy-as-potential-approach-for-treatment-of-acetaminophen-hepatotoxicity
#6
Miroslav Dinić, Jovanka Lukić, Jelena Djokić, Marina Milenković, Ivana Strahinić, Nataša Golić, Jelena Begović
The aim of this study was to investigate the potential of postbiotics originated from Lactobacillus fermentum BGHV110 strain (HV110) to counteract acetaminophen (APAP)-induced hepatotoxicity in HepG2 cells. This strain was selected according to its autophagy inducing potential, based on previous studies reporting protective role of autophagy in APAP caused cellular damage. Cell viability was assessed using MTT and LDH assays, while autophagy was monitored by qPCR analysis of BECN1, Atg5, p62/SQSTM1, and PINK1 mRNA expression and by Western blot analysis of p62/SQSTM1 and lipidated LC3 accumulation...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28421844/accuracy-of-the-paracetamol-aminotransferase-multiplication-product-to-predict-hepatotoxicity-in-modified-release-paracetamol-overdose
#7
Anselm Wong, Marco L A Sivilotti, Andis Graudins
CONTEXT: The paracetamol-aminotransferase multiplication product (APAP × ALT) is a risk predictor of hepatotoxicity that is somewhat independent of time and type of ingestion. However, its accuracy following ingestion of modified-release formulations is not known, as the product has been derived and validated after immediate-release paracetamol overdoses. OBJECTIVE: The aim of this retrospective cohort study was to evaluate the accuracy of the multiplication product to predict hepatotoxicity in a cohort of patients with modified-release paracetamol overdose...
June 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28421817/sequential-gm-csf-inhalation-after-whole-lung-lavage-for-pulmonary-alveolar-proteinosis-a-report-of-five-intractable-cases
#8
Shinya Ohkouchi, Keiichi Akasaka, Toshio Ichiwata, Shu Hisata, Hideya Iijima, Toshinori Takada, Hiroki Tsukada, Hideaki Nakayama, Jun-Ichi Machiya, Toshiya Irokawa, Hiromasa Ogawa, Yoko Shibata, Masakazu Ichinose, Masahito Ebina, Toshihiro Nukiwa, Hajime Kurosawa, Koh Nakata, Ryushi Tazawa
Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare disease characterized by the excessive accumulation of surfactant proteins within the alveolar spaces and by higher titers of autoantibodies to granulocyte/macrophage colony stimulating factor (GM-CSF) in the serum and bronchoalveolar lavage fluid (BALF). The antibodies inhibit the maturation and phagocytosis of alveolar macrophages (AMs). Although the standard therapy for aPAP has been whole-lung lavage (WLL), this procedure is invasive and needs to be repeated for several years...
April 19, 2017: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/28416868/a-synergistic-effect-of-cremophor-and-beta-glucosylceramide-to-exert-liver-and-sugar-protection
#9
Yehudit Shabat, Yaron Ilan
Many commonly used drugs carry the potential to induce hepatotoxicity, and a large number of foods and beverages induce an increase in blood sugar levels. A change in lifestyle by omitting these compounds is not applicable in many circumstances. β-Glucosylceramide (GC) is a naturally occurring glycosphingolipid that exerts an effect on the immune system. Cremophor EL (CrEL) is a synthetic, nonionic surfactant that is used as a vehicle for the administration of water-insoluble compounds. The aim of the present study was to determine the synergistic effect of oral administration of the combination of GC and CrEL (GCC) when added to potential toxic substrates or to sugar-enriched compounds...
April 2017: Journal of Food Science and Technology
https://www.readbyqxmd.com/read/28412881/glutathione-s-transferase-a1-gsta1-as-a-marker-of-acetaminophen-induced-hepatocyte-injury-in-vitro
#10
Rui Li, Fangping Liu, Yicong Chang, Xin Ma, Minmin Li, Changwen Li, Chenxi Shi, Jingshan He, Ying Li, Zhi Li, Yuexia Lin, Qing Han, Yulin Zhao, Dening Wang
Acetaminophen (APAP) overdose causes serious hepatocyte injury, and new markers are needed to predict APAP-induced hepatic injury. Glutathione S-transferase A1 (GSTA1) plays a significant role in the metabolism of APAP. Primary mouse hepatocytes were isolated by a two-step perfusion in situ. An APAP-induced hepatocyte injury model was used to characterize GSTA1 in APAP treated cells and determine whether GSTA1 could be a prognostic marker in vitro. A significant increase (p<0.05) in GSTA1 in cell culture supernatant was detected at 6 h after APAP treatment, while alanine aminotransferase (ALT), aspartate aminotransferase (AST), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) showed marked differences (p<0...
April 16, 2017: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/28412025/the-influence-of-chronic-il-6-exposure-in-vivo-on-rat-achilles-tendon-extracellular-matrix
#11
Mark S Katsma, Shivam H Patel, Erica Eldon, Kathryn A Corbell, Kevin L Shimkus, James D Fluckey, Chad C Carroll
When compared to placebo, acetaminophen (APAP) reduces tendon stiffness and collagen cross-linking. APAP also enhances the exercise-induced increase in peritendinous levels of IL-6. Elevated levels of IL-6 are associated with tendinopathy, thus we hypothesized that chronic, elevated peritendinous IL-6 would alter tendon extracellular matrix (ECM). IL-6 (∼3000pgml(-1)) was injected (3dwk(-1) for 8-wks) into the Achilles peritendinous region of male Wistar rats (n=16) with the opposite leg serving as a sham...
April 13, 2017: Cytokine
https://www.readbyqxmd.com/read/28406975/positional-therapy-in-sleep-apnoea-one-fits-all-what-determines-success-in-positional-therapy-in-sleep-apnoea-syndrome
#12
Natascha Troester, Michael Palfner, Markus Dominco, Christoph Wohlkoenig, Erich Schmidberger, Martin Trinker, Alexander Avian
INTRODUCTION: Positional therapy is a simple means of therapy in sleep apnoea syndrome, but due to controversial or lacking evidence, it is not widely accepted as appropriate treatment. In this study, we analysed data to positional therapy with regard to successful reduction of AHI and predictors of success. METHODS: All consecutive patients undergoing polysomnography between 2007 and 2011 were analysed. We used a strict definition of positional sleep apnoea syndrome (supine-exclusive sleep apnoea syndrome) and of therapy used...
2017: PloS One
https://www.readbyqxmd.com/read/28394582/multiplex-paper-based-colorimetric-dna-sensor-using-pyrrolidinyl-peptide-nucleic-acid-induced-agnps-aggregation-for-detecting-mers-cov-mtb-and-hpv-oligonucleotides
#13
Prinjaporn Tee-Ngam, Weena Siangproh, Adisorn Tuantranont, Tirayut Vilaivan, Orawon Chailapakul, Charles S Henry
The development of simple fluorescent and colorimetric assays that enable point-of-care DNA and RNA detection has been a topic of significant research because of the utility of such assays in resource limited settings. The most common motifs utilize hybridization to a complementary detection strand coupled with a sensitive reporter molecule. Here, apaper-based colorimetric assay for DNA detection based on pyrrolidinyl peptide nucleic acid (acpcPNA)-induced nanoparticle aggregationis reported as an alternative to traditional colorimetric approaches...
April 10, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28376392/multi-targeted-protection-of-acetaminophen-induced-hepatotoxicity-in-mice-by-tannic-acid
#14
Jianping Zhang, Qiongtao Song, Xue Han, Yuanyuan Zhang, Ying Zhang, Xuan Zhang, Xi Chu, Fenghua Zhang, Li Chu
Tannic acid (TA) is the polyphenol that has beneficial health effects against oxidative stress. However, the hepatoprotective effects of TA are still relatively unknown. In the present study, we evaluated the effects of TA on an acetaminophen (APAP)-induced hepatotoxicity model, which was established by administration of 400mg/kg of APAP. The levels of alanine transferase (ALT), aspartate transferase (AST), dendothelin-1 (ET-1), nitric oxide (NO) and malondialdehyde (MDA) in the APAP-induced hepatotoxicity mice were significantly increased (up to ~200%), while their levels were reduced by pretreatment with TA (25 and 50mg/kg) (P<0...
April 1, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28359199/protective-effect-of-cymbopogon-citratus-essential-oil-in-experimental-model-of-acetaminophen-induced-liver-injury
#15
Nancy Sayuri Uchida, Saulo Euclides Silva-Filho, Rafael Pazinatto Aguiar, Luiz Alexandre Marques Wiirzler, Gabriel Fernando Esteves Cardia, Heitor Augusto Otaviano Cavalcante, Francielli Maria de Souza Silva-Comar, Tânia Cristina Alexandrino Becker, Expedito Leite Silva, Ciomar Aparecida Bersani-Amado, Roberto Kenji Nakamura Cuman
To investigate the hepatoprotective effect of Cymbopogon citratus or lemongrass essential oil (LGO), it was used in an animal model of acute liver injury induced by acetaminophen (APAP). Swiss mice were pretreated with LGO (125, 250 and 500[Formula: see text]mg/kg) and SLM (standard drug, 200[Formula: see text]mg/kg) for a duration of seven days, followed by the induction of hepatotoxicity of APAP (single dose, 250[Formula: see text]mg/kg). The liver function markers alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and gamma-glutamyl transferase were determined to evaluate the hepatoprotective effects of the LGO...
March 30, 2017: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/28341123/acetaminophen-analog-n-acetyl-m-aminophenol-but-not-its-reactive-metabolite-n-acetyl-p-benzoquinone-imine-induces-cyp3a-activity-via-inhibition-of-protein-degradation
#16
Masataka Santoh, Seigo Sanoh, Yuya Ohtsuki, Yoko Ejiri, Yaichiro Kotake, Shigeru Ohta
Cytochrome P450 (CYP) 3A subfamily members are known to metabolize various types of drugs, highlighting the importance of understanding drug-drug interactions (DDI) depending on CYP3A induction or inhibition. While transcriptional regulation of CYP3A members is widely understood, post-translational regulation needs to be elucidated. We previously reported that acetaminophen (APAP) induces CYP3A activity via inhibition of protein degradation and proposed a novel DDI concept. N-Acetyl-p-benzoquinone imine (NAPQI), the reactive metabolite of APAP formed by CYP, is known to cause adverse events related to depletion of intracellular reduced glutathione (GSH)...
March 21, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28337667/self-assembled-polyelectrolyte-complexes-films-as-efficient-compression-coating-layers-for-controlled-releasing-tablets
#17
Wenyan Li, Mengmeng Huo, Arka Sen Chaudhuri, Chen Yang, Dazhong Cao, Zhenghong Wu, Xiaole Qi
Currently, polysaccharide-based hydrogels are widely studied macromolecular networks to modify drug dissolution from controlled-releasing matrix tablets. Among them, polyelectrolyte complexes (PEC) films consisted of chitosan (CS) and sodium alginate (SA) could be obtained via spontaneously assembling under physiological gastrointestinal environment. Here, we utilized these self-assembled PEC films as an efficient coating materials to develop controlled-released matrix tablets through compression coating process, with paracetamol (APAP) as model drug...
May 2017: Journal of Materials Science. Materials in Medicine
https://www.readbyqxmd.com/read/28330995/hepatic-fcrn-regulates-albumin-homeostasis-and-susceptibility-to-liver-injury
#18
Michal Pyzik, Timo Rath, Timothy T Kuo, Sanda Win, Kristi Baker, Jonathan J Hubbard, Rosa Grenha, Amit Gandhi, Thomas D Krämer, Adam R Mezo, Zachary S Taylor, Kevin McDonnell, Vicki Nienaber, Jan Terje Andersen, Atsushi Mizoguchi, Laurence Blumberg, Shalaka Purohit, Susan D Jones, Greg Christianson, Wayne I Lencer, Inger Sandlie, Neil Kaplowitz, Derry C Roopenian, Richard S Blumberg
The neonatal crystallizable fragment receptor (FcRn) is responsible for maintaining the long half-life and high levels of the two most abundant circulating proteins, albumin and IgG. In the latter case, the protective mechanism derives from FcRn binding to IgG in the weakly acidic environment contained within endosomes of hematopoietic and parenchymal cells, whereupon IgG is diverted from degradation in lysosomes and is recycled. The cellular location and mechanism by which FcRn protects albumin are partially understood...
April 4, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28330786/investigating-acetaminophen-hepatotoxicity-in-multi-cellular-organotypic-liver-models
#19
Sophia M Orbach, Margaret E Cassin, Marion F Ehrich, Padmavathy Rajagopalan
In vivo studies clearly demonstrate the participation and subsequent death of non-parenchymal liver cells (NPCs) with corresponding hepatocyte effects. This results in a critical need to investigate how major liver cell types function cohesively during hepatotoxicity. However, virtually no studies replicate these phenomena in vitro. We report the design of multi-cellular three-dimensional (3D) organotypic liver models of primary rat hepatocytes, liver sinusoidal endothelial cells (LSECs) and Kupffer cells (KCs)...
March 19, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28295449/hepatic-mtdna-tlr9-microrna-223-forms-a-negative-feedback-loop-to-limit-neutrophil-over-activation-and-acetaminophen-hepatotoxicity
#20
Yong He, Dechun Feng, Man Li, Yanhang Gao, Teresa Ramirez, Haixia Cao, Seung-Jin Kim, Yang Yang, Yan Cai, Cynthia Ju, Hua Wang, Jun Li, Bin Gao
Acetaminophen (APAP) overdose is a leading cause of acute liver failure worldwide, in which mitochondrial DNA (mtDNA) released by damaged hepatocytes activates neutrophils via the binding of TLR9, further aggravating liver injury. Here, we demonstrated that mtDNA/TLR9 also activates a negative feedback pathway via the induction of microRNA-223 (miR-223) to limit neutrophil over-activation and liver injury. After injection of APAP in mice, levels of miR-223, the most abundant miRNAs in neutrophils, were highly elevated in neutrophils...
March 13, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
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