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https://www.readbyqxmd.com/read/28295449/hepatic-mtdna-tlr9-microrna-223-forms-a-negative-feedback-loop-to-limit-neutrophil-over-activation-and-acetaminophen-hepatotoxicity
#1
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/28293265/iridoid-glycosides-fraction-isolated-from-veronica-ciliata-fisch-protects-against-acetaminophen-induced-liver-injury-in-mice
#2
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
#3
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
#4
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
#5
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/28278092/removal-of-acetaminophen-in-water-by-laccase-immobilized-in-barium-alginate
#6
Karnika Ratanapongleka, Supot Punbut
Acetaminophen (APAP) is a widely used analgesic drug. The quantities of acetaminophen excreted from human body via urine and feces are increasingly discharged into wastewaters from hospitals and household as well as found in wastewater from pharmaceutical production processes. This research has focused on the optimization of immobilized laccase condition and utilization in degradation of acetaminophen contaminated in aqueous. Laccase from Lentinus polychrous was immobilized in barium alginate. The effects of laccase immobilization such as sodium alginate concentration, barium chloride concentration and gelation time were studied...
March 1, 2017: Environmental Technology
https://www.readbyqxmd.com/read/28276273/comparative-analysis-of-length-of-stay-hospitalization-costs-opioid-use-and-discharge-status-among-spine-surgery-patients-with-postoperative-pain-management-including-intravenous-versus-oral-acetaminophen
#7
Ryan N Hansen, An T Pham, Elaine A Böing, Belinda Lovelace, George J Wan, Timothy E Miller
BACKGROUND: Recovery from spine surgery is oriented toward restoring functional health outcomes while reducing resource use. Optimal pain management is a key to reaching these objectives. We compared outcomes of spine surgery patients who received standard pain management including intravenous (IV) acetaminophen (APAP) vs. oral APAP. METHODS: We performed a retrospective analysis of the Premier database (January 2012 to September 2015) comparing spine surgery patients who received pain management with IV APAP to those who received oral APAP, with no exclusions based on additional pain management...
March 9, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28272341/liver-effects-of-clinical-drugs-differentiated-in-human-liver-slices
#8
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/28262248/hepatoprotective-hemiterpene-glycosides-from-the-rhizome-of-cibotium-barometz-l-j-sm
#9
Mei-Ping Xie, Lan Li, Hua Sun, An-Qi Lu, Bo Zhang, Jian-Gong Shi, Dan Zhang, Su-Juan Wang
Five previously undescribed hemiterpene glycosides, cibotiumbarosides E-I, and two known hemiterpene glucosides, were isolated from the rhizome of Cibotium barometz (L.) J. Sm. The structures of cibotiumbarosides E-I were established by 1D and 2D NMR spectroscopic analyses and HRMS. The absolute configuration of the aglycone of cibotiumbaroside E was assigned by calculated ECD with the TDDFT method. Cibotiumbarosides F and I both exhibited remarkable hepatoprotective activity against APAP-induced acute liver damage in vitro, which were more effective than the positive control, bicyclol...
March 2, 2017: Phytochemistry
https://www.readbyqxmd.com/read/28246450/protective-effect-of-rutin-in-comparison-to-silymarin-against-induced-hepatotoxicity-in-rats
#10
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/28236354/synthetic-biomarker-design-using-analyte-responsive-acetaminophen
#11
Tatsuya Nishihara, Joe Inoue, Sho Tabata, Shinnosuke Murakami, Takamasa Ishikawa, Natsumi Saito, Shinji Fukuda, Masaru Tomita, Tomoyoshi Soga
The use of synthetic biomarkers is an emerging technique to improve disease diagnosis. Here, we report a novel design strategy using analyte-responsive acetaminophen (APAP) to expand the catalog of analytes available for synthetic biomarker development. As a proof-of-concept, we designed hydrogen peroxide (H₂O₂)-responsive APAP (HR-APAP) and succeeded in H₂O₂ detection with cellular and animal experiments. In fact, using blood samples following HR-APAP injection, we demonstrated that the plasma concentration ratio of [APAP + APAP conjugates]/[HR-APAP] could accurately represent differences of in vivo H₂O₂ levels...
February 25, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28225807/increased-liver-specific-proteins-in-circulating-extracellular-vesicles-as-potential-biomarkers-for-drug-and-alcohol-induced-liver-injury
#12
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/28216953/therapeutic-potential-of-alpha-ketoglutarate-against-acetaminophen-induced-hepatotoxicity-in-rats
#13
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
https://www.readbyqxmd.com/read/28210203/wnt-%C3%AE-catenin-signaling-drives-thioacetamide-mediated-heteroprotection-against-acetaminophen-induced-lethal-liver-injury
#14
Vivekkumar P Dadhania, Bharat Bhushan, Udayan Apte, Harihara M Mehendale
Preplacement of compensatory tissue repair (CTR) by exposure to a nonlethal dose of a toxicant protects animals against a lethal dose of another toxicant. Although CTR is known to heteroprotect, the underlying molecular mechanisms are not completely known. Here, we investigated the mechanisms of heteroprotection using thioacetamide (TA): acetaminophen (APAP) heteroprotection model. Male Swiss Webster mice received a low dose of TA or distilled water (DW) vehicle 24 hours prior to a lethal dose of APAP. Liver injury, tissue repair, and promitogenic signaling were studied over a time course of 24 hours after APAP overdose to the TA- and DW-primed mice (TA + APAP and DW + APAP, respectively)...
January 2017: Dose-response: a Publication of International Hormesis Society
https://www.readbyqxmd.com/read/28209544/sestrin2-protects-against-acetaminophen-induced-liver-injury
#15
Seung Jung Kim, Kyu Min Kim, Ji Hye Yang, Sam Seok Cho, Sang Kyu Lee, Sae Kwang Ku, Il Je Cho, Sung Hwan Ki
Acetaminophen (APAP) overdose accounts for half of the cases of acute liver failure worldwide. We previously reported that that Sestrin2 (Sesn2) protects against d-galactosamine/lipopolysaccharide-induced acute fulminant liver failure. In this study, we demonstrated that Sesn2 protects APAP-induced liver injury in mice, using a recombinant adenovirus encoding Sesn2 (Ad-Sesn2). First, we found that treatment of mice with toxic levels of APAP significantly reduced Sesn2 expression. Tail-vein injection with Ad-Sesn2 inhibited APAP-induced serum alanine aminotransferase and aspartate aminotransferase levels and markedly reduced hepatocyte degeneration and inflammatory cell infiltration...
February 13, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28208250/simultaneous-voltammetric-determination-of-acetaminophen-and-isoniazid-hepatotoxicity-related-drugs-utilizing-bismuth-oxide-nanorod-modified-screen-printed-electrochemical-sensing-platforms
#16
Bahaa G Mahmoud, Mohamed Khairy, Farouk A Rashwan, Craig E Banks
To overcome the recent outbreaks of hepatotoxicity-related drugs, a new analytical tool for the continuously determination of these drugs in human fluids is required. Electrochemical-based analytical methods offer an effective, rapid, and simple tool for on-site determination of various organic and inorganic species. However, the design of a sensitive, selective, stable, and reproducible sensor is still a major challenge. In the present manuscript, a facile, one-pot hydrothermal synthesis of bismuth oxide (Bi2O2...
February 7, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28205631/immature-mice-are-more-susceptible-than-adult-mice-to-acetaminophen-induced-acute-liver-injury
#17
Yan Lu, Cheng Zhang, Yuan-Hua Chen, Hua Wang, Zhi-Hui Zhang, Xi Chen, De-Xiang Xu
Acetaminophen (APAP) overdose induces acute liver injury. The aim of the present study was to analyze the difference of susceptibility between immature and adult mice to APAP-induced acute liver injury. Weanling immature and adult mice were injected with APAP (300 mg/kg). As expected, immature mice were more susceptible than adult mice to APAP-induced acute liver injury. APAP-evoked hepatic c-Jun N-terminal kinase phosphorylation was stronger in immature mice than in adult mice. Hepatic receptor-interacting protein (RIP)1 was obviously activated at APAP-exposed immature and adult mice...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28197107/augmentation-of-psychotherapy-through-alternative-preconscious-priming-a-case-series-exploring-effects-on-residual-symptoms
#18
Melha Zidani, Jean-Sébastien Audet, François Borgeat, Frederick Aardema, Kieron Philip O'Connor, Yasser Khazaal
The current paper describes a case series using a new strategy for facilitating change based on Augmentation of Psychotherapy through Alternative Preconscious Priming (APAP) (1) in the treatment of eight treatment-resistant patients suffering from social phobia or generalized anxiety disorder. The patients had previously only shown a partial response to cognitive behavioral therapy (CBT) despite good treatment adherence. The patients completed APAP using a computerized program, which consisted of three steps during which alternative, more functional thoughts and beliefs relevant to the idiosyncratic difficulties experienced by the patients were formulated...
2017: Frontiers in Psychiatry
https://www.readbyqxmd.com/read/28196650/protective-role-of-p53-in-acetaminophen-hepatotoxicity
#19
Yazhen Huo, Shutao Yin, Mingzhu Yan, Sanda Win, Tin Aung Than, Mariam Aghajan, Hongbo Hu, Neil Kaplowitz
p53 is a tumor suppressor with a pro-death role in many conditions. However, in some contexts, evidence supports a pro-survival function. p53 has been shown to be activated in acetaminophen (APAP) toxicity but the impact of this on toxicity is uncertain. In the present study, we have found that p53 plays a protective role in APAP-induced liver injury. We inhibited p53 using three different approaches in mice, pifithrin-α (PFTα), knockdown of p53 expression with antisense oligonucleotide, and p53 knockout...
February 11, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28194962/high-speed-quantitative-uplc-ms-analysis-of-multiple-amines-in-human-plasma-and-serum-via-precolumn-derivatization-with-6-aminoquinolyl-n-hydroxysuccinimidyl-carbamate-application-to-acetaminophen-induced-liver-failure
#20
Nicola Gray, Rabiya Zia, Adam King, Vishal C Patel, Julia Wendon, Mark J W McPhail, Muireann Coen, Robert S Plumb, Ian D Wilson, Jeremy K Nicholson
A targeted reversed-phase gradient UPLC-MS/MS assay has been developed for the quantification /monitoring of 66 amino acids and amino-containing compounds in human plasma and serum using precolumn derivatization with 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AccQTag Ultra). Derivatization of the target amines required minimal sample preparation and resulted in analytes with excellent chromatographic and mass spectrometric detection properties. The resulting method, which requires only 10 μL of sample, provides the reproducible and robust separation of 66 analytes in 7...
February 7, 2017: Analytical Chemistry
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