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acetaminophen and liver

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https://www.readbyqxmd.com/read/28330995/hepatic-fcrn-regulates-albumin-homeostasis-and-susceptibility-to-liver-injury
#1
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...
March 22, 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
#2
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/28321158/porcine-model-characterizing-various-parameters-assessing-the-outcome-after-acetaminophen-intoxication-induced-acute-liver-failure
#3
Karolin Thiel, Wilfried Klingert, Kathrin Klingert, Matthias H Morgalla, Martin U Schuhmann, Pamela Leckie, Yalda Sharifi, Nathan A Davies, Rajiv Jalan, Andreas Peter, Christian Grasshoff, Alfred Königsrainer, Martin Schenk, Christian Thiel
AIM: To investigate the changes of hemodynamic and laboratory parameters during the course of acute liver failure following acetaminophen overdose. METHODS: Eight pigs underwent a midline laparotomy following jejunal catheter placement for further acetaminophen intoxication and positioning of a portal vein Doppler flow-probe. Acute liver failure was realized by intrajejunal acetaminophen administration in six animals, two animals were sham operated. All animals were invasively monitored and received standardized intensive care support throughout the study...
March 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28295449/hepatic-mtdna-tlr9-microrna-223-forms-a-negative-feedback-loop-to-limit-neutrophil-over-activation-and-acetaminophen-hepatotoxicity
#4
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
https://www.readbyqxmd.com/read/28294319/grpr-antagonist-protects-from-drug-induced-liver-injury-by-impairing-neutrophil-chemotaxis-and-motility
#5
Rafael S Czepielewski, Natália Jaeger, Pedro E Marques, Maísa M Antunes, Maurício M Rigo, Débora M Alvarenga, Rafaela V Pereira, Rodrigo D da Silva, Tiago G Lopes, Vinícius D da Silva, Bárbara N Porto, Gustavo B Menezes, Cristina Bonorino
Drug-induced liver injury (DILI) is a major cause of acute liver failure (ALF), where hepatocyte necrotic products trigger liver inflammation, release of CXCR2 ligands (IL-8) and other neutrophil chemotactic molecules. Liver infiltration by neutrophils is a major cause of the life threatening tissue damage that ensues. A GRPR (gastrin-releasing peptide receptor) antagonist impairs IL-8-induced neutrophil chemotaxis in vitro. We investigated its potential to reduce acetaminophen-induced ALF, neutrophil migration and mechanisms underlying this phenomenon...
March 10, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28293919/-extracorporeal-liver-support-of-liver-failure
#6
Hans Ulrich Gerth, Michele Pohlen, Hermann Pavenstädt, Hartmut Schmidt
Extracorporeal liver support can be classified into cell-free, artificial methods (artificial liver support, ALS) and cell-based bioartificial methods (bioartificial liver support, BLS). ALS improves biochemical parameters of liver failure by the simultaneous removal of protein-bound and water-soluble substances. Here, the MARS therapy belongs to the most studied methods with a proved beneficial effect on hepatic encephalopathy (HE), hepatorenal syndrome (HRS) or hyperbilirubinemia. However, a general survival advantage of any liver support for liver failure has not been shown yet and is restricted to meta-analyses or patient subgroups...
March 14, 2017: Zeitschrift Für Gastroenterologie
https://www.readbyqxmd.com/read/28293265/iridoid-glycosides-fraction-isolated-from-veronica-ciliata-fisch-protects-against-acetaminophen-induced-liver-injury-in-mice
#7
Shancai Tan, Qiuxia Lu, Yueyue Shu, Yiran Sun, Fang Chen, Lin Tang
Veronica ciliata Fisch. has traditionally been used in Tibetan medicine for the treatment of hepatitis, cholecystitis, rheumatism, and urticaria. We analyzed the chemical composition of the iridoid glycosides fraction (IGF) isolated from V. ciliata and evaluated the antioxidant and hepatoprotective properties. The IGF was separated by high-speed countercurrent chromatography (HSCCC) and the main compounds were identified by ultra-performance liquid chromatography coupled to a photodiode array. We determined the in vitro antioxidant ability of the IGF through radical scavenging assays and assessed the in vivo hepatoprotective potential in an acetaminophen- (APAP-) induced acute liver injury murine model...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28291796/the-effect-of-acetaminophen-on-ubiquitin-homeostasis-in-saccharomyces-cerevisiae
#8
Angelina Huseinovic, Jolanda S van Leeuwen, Tibor van Welsem, Iris Stulemeijer, Fred van Leeuwen, Nico P E Vermeulen, Jan M Kooter, J Chris Vos
Acetaminophen (APAP), although considered a safe drug, is one of the major causes of acute liver failure by overdose, and therapeutic chronic use can cause serious health problems. Although the reactive APAP metabolite N-acetyl-p-benzoquinoneimine (NAPQI) is clearly linked to liver toxicity, toxicity of APAP is also found without drug metabolism of APAP to NAPQI. To get more insight into mechanisms of APAP toxicity, a genome-wide screen in Saccharomyces cerevisiae for APAP-resistant deletion strains was performed...
2017: PloS One
https://www.readbyqxmd.com/read/28286920/blockade-of-notch-signaling-promotes-acetaminophen-induced-liver-injury
#9
Longfeng Jiang, Michael Ke, Shi Yue, Wen Xiao, Youde Yan, Xiaozhao Deng, Qi-Long Ying, Jun Li, Bibo Ke
Liver injury after experimental acetaminophen treatment is mediated both by direct hepatocyte injury through a P450-generated toxic metabolite and indirectly by activated liver Kupffer cells and neutrophils. This study was designed to investigate the role of Notch signaling in the regulation of innate immune responses in acetaminophen (APAP)-induced liver injury. Using a mouse model of APAP-induced liver injury, wild-type (WT) and toll-like receptor 4 knockout (TLR4 KO) mice were injected intraperitoneally with APAP or PBS...
March 13, 2017: Immunologic Research
https://www.readbyqxmd.com/read/28286204/long-term-acetaminophen-treatment-induced-liver-fibrosis-in-mice-and-the-involvement-of-egr-1
#10
Qingyun Bai, Hongyu Yan, Yuchen Sheng, Yao Jin, Liang Shi, Lili Ji, Zhengtao Wang
Acetaminophen (APAP)-induced acute liver injury has already been well studied. However, whether long-term administration of APAP will cause liver fibrosis is still not very clear. This study aims to investigate the liver fibrosis in mice induced by long-term APAP treatment and the involvement of early growth response 1 (Egr-1). C57BL/6 mice were orally given with APAP (200, 300mg/kg) for 2, 6 or 10 weeks, respectively. Liver hydroxyproline content, collagen deposition and inflammatory cells infiltration were increased in mice treated with APAP (200, 300mg/kg) for 6 or 10 weeks...
March 9, 2017: Toxicology
https://www.readbyqxmd.com/read/28272341/liver-effects-of-clinical-drugs-differentiated-in-human-liver-slices
#11
Alison E M Vickers, Anatoly V Ulyanov, Robyn L Fisher
Drugs with clinical adverse effects are compared in an ex vivo 3-dimensional multi-cellular human liver slice model. Functional markers of oxidative stress and mitochondrial function, glutathione GSH and ATP levels, were affected by acetaminophen (APAP, 1 mM), diclofenac (DCF, 1 mM) and etomoxir (ETM, 100 μM). Drugs targeting mitochondria more than GSH were dantrolene (DTL, 10 μM) and cyclosporin A (CSA, 10 μM), while GSH was affected more than ATP by methimazole (MMI, 500 μM), terbinafine (TBF, 100 μM), and carbamazepine (CBZ 100 μM)...
March 7, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28272093/elevated-procalcitonin-is-associated-with-bacterial-infection-during-acute-liver-failure-only-when-unrelated-to-acetaminophen-intoxication
#12
Maxime Mallet, Maela Haq, Simona Tripon, Maguy Bernard, Hedi Benosman, Dominique Thabut, Marika Rudler
AIM: The aim of this study was to evaluate the accuracy of procalcitonin (PCT) in predicting bacterial infection and survival without transplantation upon admission in the ICU for acute liver failure (ALF). PATIENTS AND METHODS: From January 2009 until October 2015, all cases of ALF patients admitted in our ICU were retrospectively reviewed and included in the study if the PCT level upon admission was available. Patients with pre-existing liver pathology or ALF in a context of already advanced multiorgan failure were excluded...
March 7, 2017: European Journal of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28255555/procalcitonin-impairs-liver-cell-viability-and-function-in-vitro-a-potential-new-mechanism-of-liver-dysfunction-and-failure-during-sepsis
#13
Martin Sauer, Sandra Doß, Johannes Ehler, Thomas Mencke, Nana-Maria Wagner
Purpose. Liver dysfunction and failure are severe complications of sepsis and result in poor outcome and increased mortality. The underlying pathologic mechanisms of hepatocyte dysfunction and necrosis during sepsis are only incompletely understood. Here, we investigated whether procalcitonin, a biomarker of sepsis, modulates liver cell function and viability. Materials and Methods. Employing a previously characterized and patented biosensor system evaluating hepatocyte toxicity in vitro, human hepatocellular carcinoma cells (HepG2/C3A) were exposed to 0...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28253482/aav-nrf2-promotes-protection-and-recovery-in-animal-models-of-oxidative-stress
#14
Katharine J Liang, Kenton T Woodard, Mark A Weaver, John Paul Gaylor, Ellen R Weiss, R Jude Samulski
NRF2 is a transcription factor that drives antioxidant gene expression in multiple organ systems. We hypothesized that Nrf2 overexpression could be therapeutically applied toward diseases in which redox homeostasis is disrupted. In this study, adeno-associated virus (AAV)-Nrf2 was tested in a mouse model of acute acetaminophen-induced liver toxicity and successfully conferred protection from hepatotoxicity, validating the vector design and early onset of NRF2-mediated protection. Furthermore, therapeutic potential of AAV-Nrf2 in chronic disease also was tested in a light-induced mouse model of age-related macular degeneration...
March 1, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28246565/diphenhydramine-as-a-cause-of-drug-induced-liver-injury
#15
Yunseok Namn, Yecheskel Schneider, Isabelle H Cui, Arun Jesudian
Drug-induced liver injury (DILI) is the most common cause of acute liver failure in the Unites States and accounts for 10% of acute hepatitis cases. We report the only known case of diphenhydramine-induced acute liver injury in the absence of concomitant medications. A 28-year-old man with history of 13/14-chromosomal translocation presented with fevers, vomiting, and jaundice. Aspartate-aminotransferase and alanine-aminotransferase levels peaked above 20,000 IU/L and 5,000 IU/L, respectively. He developed coagulopathy but without altered mental status...
2017: Case Reports in Hepatology
https://www.readbyqxmd.com/read/28246450/protective-effect-of-rutin-in-comparison-to-silymarin-against-induced-hepatotoxicity-in-rats
#16
M Kasi Reddy, A Gopala Reddy, B Kala Kumar, D Madhuri, G Boobalan, M Anudeep Reddy
AIM: The aim of this study is to evaluate the hepatoprotective effect of rutin (RTN) in comparison to silymarin (SLM) against acetaminophen (APAP)-induced hepatotoxicity in rats. MATERIALS AND METHODS: Male Wistar albino rats (n=24) of 3 months age were equally divided into four groups. Group 1 served as normal control. Hepatotoxicity was induced in the remaining three groups with administration of 500 mg/kg po APAP from day 1-3. Groups 2, 3, and 4 were subsequently administered orally with distilled water, 25 mg/kg of SLM, and 20 mg/kg of RTN, respectively, for 11 days...
January 2017: Veterinary World
https://www.readbyqxmd.com/read/28225807/increased-liver-specific-proteins-in-circulating-extracellular-vesicles-as-potential-biomarkers-for-drug-and-alcohol-induced-liver-injury
#17
Young-Eun Cho, Eun-Ju Im, Pyong-Gon Moon, Esteban Mezey, Byoung-Joon Song, Moon-Chang Baek
Drug- and alcohol-induced liver injury are a leading cause of liver failure and transplantation. Emerging evidence suggests that extracellular vesicles (EVs) are a source of biomarkers because they contain unique proteins reflecting the identity and tissue-specific origin of the EV proteins. This study aimed to determine whether potentially hepatotoxic agents, such as acetaminophen (APAP) and binge alcohol, can increase the amounts of circulating EVs and evaluate liver-specific EV proteins as potential biomarkers for liver injury...
2017: PloS One
https://www.readbyqxmd.com/read/28219698/protective-effects-of-diallyl-disulfide-against-acetaminophen-induced-nephrotoxicity-a-possible-role-of-cyp2e1-and-nf-%C3%AE%C2%BAb
#18
Je-Won Ko, Jin-Young Shin, Jeong-Won Kim, Sung-Hyeuk Park, Na-Rae Shin, In-Chul Lee, In-Sik Shin, Changjong Moon, Sung-Ho Kim, Sung-Hwan Kim, Jong-Choon Kim
Diallyl disulfide (DADS) is a degradation product of allicin which is contained in garlic. This study investigated the protective effects of DADS against acetaminophen (AAP)-induced nephrotoxicity and the molecular mechanisms of nephroprotective effects in rats. AAP caused severe nephrotoxicity as evidenced by significant increases in renal tubular cell apoptosis, mitochondria-mediated apoptosis, and up-regulation of nuclear transcription factor kappa-B (NF-κB), cyclooxygenase-2 (Cox-2), and tumor necrosis factor-α (TNF-α) in the kidney with histopathological alterations...
February 17, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28219592/urgent-liver-transplantation-for-dietary-supplements-an-under-recognized-problem
#19
L L Wong, L Lacar, M Roytman, S L Orloff
BACKGROUND: The recent outbreak of acute liver failure caused by herbal/dietary supplements (HDS) in Hawaii prompted evaluation of those patients who underwent emergency liver transplantation (LT) for HDS in the United States. METHODS: We queried the Scientific Registry of Transplant Recipients (2003-2015) to identify patients who underwent urgent LT for acute hepatic necrosis (AHN) and identified those with HDS use. This group of patients was then characterized...
March 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28216953/therapeutic-potential-of-alpha-ketoglutarate-against-acetaminophen-induced-hepatotoxicity-in-rats
#20
Lalita Mehra, Yasha Hasija, Gaurav Mittal
OBJECTIVE: Alpha-ketoglutarate (α-KG) is a cellular intermediary metabolite of Krebs cycle, involved in energy metabolism, amino acid synthesis, and nitrogen transport. It is available over-the-counter and marketed as a nutritional supplement. There is a growing body of evidence to suggest that dietary α-KG has the potential to maintain cellular redox status and thus can protect various oxidative stress induced disease states. The aim of the present study was to investigate the hepatoprotective role of α-KG in acetaminophen (APAP) induced toxicity in rats...
October 2016: Journal of Pharmacy & Bioallied Sciences
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