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acetaminophen and liver

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https://www.readbyqxmd.com/read/28440304/the-natural-history-of-severe-acute-liver-injury
#1
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/28438567/a-systematic-evaluation-of-micrornas-in-regulating-human-hepatic-cyp2e1
#2
Yong Wang, Dianke Yu, William H Tolleson, Li-Rong Yu, Bridgett Green, Linjuan Zeng, Yinting Chen, Si Chen, Zhen Ren, Lei Guo, Weida Tong, Huaijin Guan, Baitang Ning
Cytochrome P450 2E1 (CYP2E1) is an important drug metabolizing enzyme for processing numerous xenobiotics in the liver, including acetaminophen and ethanol. Previous studies have shown that microRNAs (miRNAs) can suppress CYP2E1 expression by binding to the 3'-untranslated region (3'-UTR) of its transcript. However, a systematic analysis of CYP2E1 regulation by miRNAs has not been described. Here, we applied in silico, in vivo, and in vitro approaches to investigate miRNAs involved in the regulation of CYP2E1...
April 21, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28436611/co-ingestion-of-willow-bark-tea-and-acetaminophen-associated-with-fatal-infantile-fulminant-liver-failure
#3
Deepak Dinakaran, Erin Bristow, Hanan Armanious, Daniel Garros, Jason Yap, Michelle Noga, Consolato Sergi
No abstract text is available yet for this article.
April 24, 2017: Pediatrics International: Official Journal of the Japan Pediatric Society
https://www.readbyqxmd.com/read/28435131/repression-of-acetaminophen-induced-hepatotoxicity-by-a-combination-of-celastrol-and-brilliant-blue-g
#4
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
#5
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
#6
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/28416868/a-synergistic-effect-of-cremophor-and-beta-glucosylceramide-to-exert-liver-and-sugar-protection
#7
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
#8
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/28410455/diallyl-polysulfides-from-allium-sativum-as-immunomodulators-hepatoprotectors-and-antimycobacterial-agents
#9
Carel Oosthuizen, Miriam Arbach, Debra Meyer, Chris Hamilton, Namrita Lall
Mycobacterium tuberculosis remains one of the world's deadliest killers, with an annual death rate of ∼1.5 million. The medicinal effects of garlic have been well documented, and natural products have been shown to have antimycobacterial activity. The current study evaluated the efficacy of six Allium sativum L. polysulfide mixtures as antimycobacterial agents together with their cytotoxic, immunomodulatory, and hepatoprotective activities. The microtitre PrestoBlue assay was used to determine the minimum inhibitory concentrations (MIC)...
April 14, 2017: Journal of Medicinal Food
https://www.readbyqxmd.com/read/28409533/control-of-oxygen-tension-recapitulates-zone-specific-functions-in-human-liver-microphysiology-systems
#10
Felipe T Lee-Montiel, Subin M George, Albert H Gough, Anup D Sharma, Juanfang Wu, Richard DeBiasio, Lawrence A Vernetti, D Lansing Taylor
This article describes our next generation human Liver Acinus MicroPhysiology System (LAMPS). The key demonstration of this study was that Zone 1 and Zone 3 microenvironments can be established by controlling the oxygen tension in individual devices over the range of ca. 3 to 13%. The oxygen tension was computationally modeled using input on the microfluidic device dimensions, numbers of cells, oxygen consumption rates of hepatocytes, the diffusion coefficients of oxygen in different materials and the flow rate of media in the MicroPhysiology System (MPS)...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28386382/protective-effects-of-an-ethanol-extract-of-angelica-keiskei-against-acetaminophen-induced-hepatotoxicity-in-hepg2-and-heparg-cells
#11
Yoon-Hee Choi, Hyun Sook Lee, Cha-Kwon Chung, Eun Ji Kim, Il-Jun Kang
BACKGROUND/OBJECTIVE: Although Angelica keiskei (AK) has widely been utilized for the purpose of general health improvement among Asian, its functionality and mechanism of action. The aim of this study was to determine the protective effect of ethanol extract of AK (AK-Ex) on acute hepatotoxicity induced by acetaminophen (AAP) in HepG2 human hepatocellular liver carcinoma cells and HepaRG human hepatic progenitor cells. MATERIALS/METHODS: AK-Ex was prepared HepG2 and HepaRG cells were cultured with various concentrations and 30 mM AAP...
April 2017: Nutrition Research and Practice
https://www.readbyqxmd.com/read/28379590/hepatotoxicity-of-paracetamol-and-related-fatalities
#12
R Tittarelli, M Pellegrini, M G Scarpellini, E Marinelli, V Bruti, N M di Luca, F P Busardò, S Zaami
Paracetamol, also known as acetaminophen, is the most commonly used antipyretic and pain reliever and since 1955 it is available over-the-counter as a single formulation or in combination with other substances and, as indicated by the World Health Organization, it can be used in all the three steps of pain intensity. Paracetamol toxicity is one of the most common causes of poisoning worldwide. While paracetamol is described as relatively nontoxic when administered in therapeutic doses, it is known to cause toxicity when taken in a single or repeated high dose, or after chronic ingestion...
March 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28376392/multi-targeted-protection-of-acetaminophen-induced-hepatotoxicity-in-mice-by-tannic-acid
#13
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/28373282/metformin-directly-binds-the-alarmin-hmgb1-and-inhibits-its-proinflammatory-activity
#14
Takahiro Horiuchi, Natsumi Sakata, Yoshihiro Narumi, Tomohiro Kimura, Takashi Hayashi, Keisuke Nagano, Keyue Liu, Masahiro Nishibori, Sohei Tsukita, Tetsuya Yamada, Hideki Katagiri, Ryutaro Shirakawa, Hisanori Horiuchi
Metformin is the first-line drug in the treatment of type 2 diabetes. In addition to its hypoglycemic effect, metformin has an anti-inflammatory function, but the precise mechanism promoting this activity remains unclear. High mobility group box 1 (HMGB1) is an alarmin that is released from necrotic cells and induces inflammatory responses by its cytokine-like activity and is therefore a target of anti-inflammatory therapies. Here we identified HMGB1 as a novel metformin binding protein by affinity purification using a biotinylated metformin analogue...
April 3, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28366990/hepatoprotective-effects-of-rice-derived-peptides-against-acetaminophen-induced-damage-in-mice
#15
Kayoko Kawakami, Chie Moritani, Misugi Uraji, Akiko Fujita, Koji Kawakami, Tadashi Hatanaka, Etsuko Suzaki, Seiji Tsuboi
Glutathione, the most abundant intracellular antioxidant, protects cells against reactive oxygen species induced oxidative stress and regulates intracellular redox status. We found that rice peptides increased intracellular glutathione levels in human hepatoblastoma HepG2 cells. 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 rice peptides on acetaminophen-induced hepatotoxicity in mice...
March 2017: Journal of Clinical Biochemistry and Nutrition
https://www.readbyqxmd.com/read/28363639/increased-expression-of-ctla4-by-t-cells-induced-by-b7-in-sera-reduces-adaptive-immunity-in-patients-with-acute-liver-failure
#16
Wafa Khamri, Robin D Abeles, Tie Zheng Hou, Amy E Anderson, Ahmed El-Masry, Evangelos Triantafyllou, Christine Bernsmeier, Fin S Larsen, Arjuna Singanayagam, Nobuaki Kudo, Lucia A Possamai, Fanny Lebosse, Georg Auzinger, William Bernal, Christopher Willars, Christopher J Weston, Giovanna Lombardi, Julia Wendon, Mark Thursz, Charalambos G Antoniades
BACKGROUND & AIMS: Patients with acute liver failure (ALF) have defects in innate immune responses to microbes (immuneparesis) and are susceptible to sepsis. Cytotoxic T-lymphocyte associated protein 4 (CTLA4), which interacts with the membrane receptor B7 (also called CD80 and CD86), is a negative regulator of T-cell activation. We collected T cells from patients with ALF and investigated whether inhibitory signals downregulate adaptive immune responses in patients with ALF. METHODS: We collected peripheral blood mononuclear cells from patients with ALF and controls from September 2013 through September 2015 (45 patients with ALF, 20 patients with acute-on-chronic liver failure, 15 patients with cirrhosis with no evidence of acute decompensation, 20 patients with septic shock but no cirrhosis or liver disease, and 20 healthy individuals)...
March 28, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28359650/corrigendum-to-differential-susceptibility-to-acetaminophen-induced-liver-injury-in-sub-strains-of-c57bl-6-mice-6n-versus-6j-food-and-chem-toxicol-98-part-b-2016-107-118
#17
Luqi Duan, John S Davis, Benjamin L Woolbright, Kuo Du, Mala Cahkraborty, James Weemhoff, Hartmut Jaeschke, Mohammed Bourdi
No abstract text is available yet for this article.
March 27, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28359199/protective-effect-of-cymbopogon-citratus-essential-oil-in-experimental-model-of-acetaminophen-induced-liver-injury
#18
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/28336158/-acetaminophen-knowledge-use-and-overdose-risk-in-urban-patients-consulting-their-general-practitioner-a-prospective-descriptive-and-transversal-study
#19
Lauriane Cipolat, Ouriel Loeb, Clotilde Latarche, Elise Pape, Pierre Gillet, Nadine Petitpain
INTRODUCTION: Acetaminophen is the most involved active substance in both unintentional and intentional drug poisoning. However, its availability outside community pharmacies is being debated in France. METHODS: We made, via a self-administered questionnaire, a prospective assessment of knowledge, use and acetaminophen overdose risk in patients consulting their general practitioner, in the Metz Métropole urban area, between May 2015 and February 2016. We estimated the prevalence of potential unintentional overdosage by capture-recapture method...
February 20, 2017: Thérapie
https://www.readbyqxmd.com/read/28336157/-prescription-of-acetaminophen-in-five-french-hospitals-what-are-the-practices
#20
Jean-Baptiste Pace, Viviane Nave, Mélanie Moulis, Magali Bourdelin, Sandra Coursier, Élodie Jean-Bart, Bertrand Leroy, Jean-Louis Bonnefous, Hervé Bontemps, Jérôme Coutet, Carine Eyssette, Emmanuelle Pont
AIM: Acetaminophen is widely used in hospital settings and often considered as nontoxic. We conducted a multicentric study in order to evaluate its proper use. METHOD: Prescriptions from five general hospitals were analyzed, according to dose adjustments required in renal or liver failure, weight or chronic alcoholism, determined using a literature review. Other criteria have been assessed: indication for parenteral access, accuracy of administration time and pain assessment...
February 22, 2017: Thérapie
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