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https://www.readbyqxmd.com/read/28109286/acetaminophen-attenuates-lipopolysaccharide-induced-cognitive-impairment-through-antioxidant-activity
#1
Wei-Xing Zhao, Jun-Han Zhang, Jiang-Bei Cao, Wei Wang, Dong-Xin Wang, Xiao-Ying Zhang, Jun Yu, Yong-Yi Zhang, You-Zhi Zhang, Wei-Dong Mi
BACKGROUND: Considerable evidence has shown that neuroinflammation and oxidative stress play an important role in the pathophysiology of postoperative cognitive dysfunction (POCD) and other progressive neurodegenerative disorders. Increasing evidence suggests that acetaminophen (APAP) has unappreciated antioxidant and anti-inflammatory properties. However, the impact of APAP on the cognitive sequelae of inflammatory and oxidative stress is unknown. The objective of this study is to explore whether APAP could have neuroprotective effects on lipopolysaccharide (LPS)-induced cognitive impairment in mice...
January 21, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28106809/new-phenylpropanoid-and-coumarin-glycosides-from-the-stems-of-hydrangea-paniculata-sieb
#2
Jie Ma, Chuang-Jun Li, Jing-Zhi Yang, Hua Sun, Dong-Ming Zhang
A new phenylpropanoid glycoside (1), and two new coumarin glycosides (2, 3), together with two known compounds (4, 5), have been isolated from the stems of Hydrangea paniculata Sieb. Their structures have been determined by spectroscopic and chemical methods. Furthermore, compound 1 (50 μM) exhibited significant hepatoprotective activity against N-acetyl-p-aminophenol (APAP)-induced HepG2 cell damage in vitro assays.
January 18, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28104395/methionine-sulfoxide-reductase-a-deficiency-exacerbates-acute-liver-injury-induced-by-acetaminophen
#3
Mahendra Pratap Singh, Ki Young Kim, Hwa-Young Kim
Acetaminophen (APAP) overdose induces acute liver injury via enhanced oxidative stress and glutathione (GSH) depletion. Methionine sulfoxide reductase A (MsrA) acts as a reactive oxygen species scavenger by catalyzing the cyclic reduction of methionine-S-sulfoxide. Herein, we investigated the protective role of MsrA against APAP-induced liver damage using MsrA gene-deleted mice (MsrA(-/-)). We found that MsrA(-/-) mice were more susceptible to APAP-induced acute liver injury than wild-type mice (MsrA(+/+))...
January 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28088388/activation-of-gr-but-not-pxr-by-dexamethasone-attenuated-acetaminophen-hepatotoxicities-via-fgf21-induction
#4
Saurabh G Vispute, Pengli Bu, Yuan Le, Xingguo Cheng
Glucocorticoid receptor (GR) signaling is indispensable for cell growth and development, and plays important roles in drug metabolism. Fibroblast growth factor (Fgf) 21, an important regulator of glucose, lipid, and energy metabolism, plays a cytoprotective role by attenuating toxicities induced by chemicals such as dioxins, acetaminophen (APAP), and alcohols. The present study investigates the impact of dexamethasone (DEX)-activated GR on Fgf21 expression and how it affects the progression of APAP-induced hepatotoxicity...
January 11, 2017: Toxicology
https://www.readbyqxmd.com/read/28086854/in-vitro-assessment-of-hepatoprotective-agents-against-damage-induced-by-acetaminophen-and-ccl4
#5
Liliana Torres González, Noemí Waksman Minsky, Linda Elsa Muñoz Espinosa, Ricardo Salazar Aranda, Jonathan Pérez Meseguer, Paula Cordero Pérez
BACKGROUND: In vitro bioassays are important in the evaluation of plants with possible hepatoprotective effects. The aims of this study were to evaluate the pretreatment of HepG2 cells with hepatoprotective agents against the damage induced by carbon tetrachloride (CCl4) and paracetamol (APAP). METHODS: Antioxidative activity was measured using an assay to measure 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging. The in vitro hepatotoxicity of CCl4 and APAP, and the cytotoxic and hepatoprotective properties of silymarin (SLM), silybinin (SLB), and silyphos (SLP) were evaluated by measuring cell viability; activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH); total antioxidant capacity (TAOxC); and reduced glutathione (GSH), superoxide dismutase (SOD), and lipid peroxidation (malondialdehyde (MDA) levels)...
January 13, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28070111/a-monkey-model-of-acetaminophen-induced-hepatotoxicity-phenotypic-similarity-to-human
#6
Satoshi Tamai, Takuma Iguchi, Noriyo Niino, Kei Mikamoto, Ken Sakurai, Ayako Sayama, Hitomi Shimoda, Wataru Takasaki, Kazuhiko Mori
Species-specific differences in the hepatotoxicity of acetaminophen (APAP) have been shown. To establish a monkey model of APAP-induced hepatotoxicity, which has not been previously reported, APAP at doses up to 2,000 mg/kg was administered orally to fasting male and female cynomolgus monkeys (n = 3-5/group) pretreated intravenously with or without 300 mg/kg of the glutathione biosynthesis inhibitor, L-buthionine-(S,R)-sulfoximine (BSO). In all the animals, APAP at 2,000 mg/kg with BSO but not without BSO induced hepatotoxicity, which was characterized histopathologically by centrilobular necrosis and vacuolation of hepatocytes...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28068511/inhibition-of-glycogen-synthase-kinase-3-accelerated-liver-regeneration-after-acetaminophen-induced-hepatotoxicity-in-mice
#7
Bharat Bhushan, Samikshya Poudel, Michael W Manley, Nairita Roy, Udayan Apte
Overdose of acetaminophen (APAP) is the leading cause of acute liver failure (ALF) in the United States. Timely initiation of compensatory liver regeneration after APAP hepatotoxicity is critical for final recovery, but the mechanisms of liver regeneration after APAP-induced ALF have not been extensively explored yet. Previous studies from our laboratory have demonstrated that activation of β-catenin signaling after APAP overdose is associated with timely liver regeneration. Herein, we investigated the role of glycogen synthase kinase 3 (GSK3) in liver regeneration after APAP hepatotoxicity using a pharmacological inhibition strategy in mice...
January 6, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28045783/quantitative-method-for-simultaneous-analysis-of-acetaminophen-and-six-metabolites
#8
Laureen A Lammers, Roos Achterbergh, Marcel C M Pistorius, Johannes A Romijn, Ron A A Mathôt
BACKGROUND: Hepatotoxicity after ingestion of high-dose acetaminophen (N-acetyl-para-aminophenol, APAP) is caused by the metabolites of the drug. To gain more insight in factors influencing susceptibility to APAP hepatotoxicity, quantification of APAP and metabolites is important. A few methods have been developed to simultaneously quantify APAP and its most important metabolites. However, these methods require a comprehensive sample preparation and long run times. The aim of this study was to develop and validate a simplified, but sensitive, method for the simultaneous quantification of acetaminophen, the main metabolites acetaminophen-glucuronide and acetaminophen-sulfate, and four Cytochrome P450-mediated metabolites by using liquid chromatography with mass spectrometric detection (LC-MS/MS)...
December 30, 2016: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28045449/assignment-of-absolute-configuration-of-a-new-hepatoprotective-schiartane-type-nortriterpenoid-using-x-ray-diffraction
#9
Xiaojuan Wang, Frank R Fronczek, Jiabao Chen, Jiabao Liu, Daneel Ferreira, Shuai Li, Mark T Hamann
A new schiartane-type nortriterpenoid, micrandilactone H was isolated from Kadsuralongipedunculata Finet et Gagnep. Its 2D (two dimension) structure was elucidated by NMR spectroscopic analysis, and it is similar to that of Kadnanolactones H and the absolute configuration was established through X-ray diffraction and ECD data analysis. This represents the first complete assignment of the absolute configuration of a schiartane-type nortriterpenoid by X-ray diffraction and the ECD method. Micrandilactone H showed moderate hepatoprotective activity against N-acetyl-p-aminophenol (APAP)-induced toxicity in HepG2 cells with cell survival rates of 56...
January 2, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28031524/adenosine-5-monophosphate-blocks-acetaminophen-toxicity-by-increasing-ubiquitination-mediated-ask1-degradation
#10
Xiao Yang, Yibei Zhan, Qi Sun, Xi Xu, Yi Kong, Jianfa Zhang
Acetaminophen (APAP) overdose is the most frequent cause of drug-induced liver failure in the world. Hepatic c-jun NH2-terminal protein kinase (JNK) activation is thought to be a consequence of oxidative stress produced during APAP metabolism. Activation of JNK signals causes hepatocellular damage with necrotic and apoptotic cell death. Here we found that APAP caused a feedback increase in plasma adenosine 5'-monophsphate (5'-AMP). We demonstrated that co-administration of APAP and 5'-AMP significantly ameliorated APAP-induced hepatotoxicity in mice, without influences on APAP metabolism and its analgesic function...
December 21, 2016: Oncotarget
https://www.readbyqxmd.com/read/28031152/lycopene-pretreatment-improves-hepatotoxicity-induced-by-acetaminophen-in-c57bl-6-mice
#11
Ana Carla Balthar Bandeira, Rafaella Cecília da Silva, Joamyr Victor Rossoni, Vivian Paulino Figueiredo, André Talvani, Silvia Dantas Cangussú, Frank Silva Bezerra, Daniela Caldeira Costa
Acetaminophen (APAP) is an antipyretic and analgesic drug that, in high doses, leads to severe liver injury and potentially death. Oxidative stress is an important event in APAP overdose. Researchers are looking for natural antioxidants with the potential to mitigate the harmful effects of reactive oxygen species in different models. Lycopene has been widely studied for its antioxidant properties. The aim of this study was to evaluate the antioxidant potential of lycopene pretreatment in APAP-induced liver injury in C57BL/6 mice...
December 18, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28011956/repeated-cures-with-paracetamol-worsen-sarcopenia-in-old-rats-with-suboptimal-food-intake
#12
C Mast, I Savary-Auzeloux, D Remond, C Pouyet, D Centeno, G Voyard, L Combaret, D Dardevet, I Papet
The availability of all amino acids is of prime importance to prevent the ageing-associated decrease in skeletal muscle mass i.e. sarcopenia. Cysteine is the precursor of sulfate and glutathione that are both utilized in the liver to detoxify paracetamol (APAP). Cysteine availability could become limiting under repeated cures with APAP, especially when food intake is suboptimal. The aim of the study was to determine whether repeated cures with APAP could worsen sarcopenia. Twenty-two-month-old male Wistar rats received 3 two-week-long cures of APAP (1% of the diet) intercalated with washout periods of two weeks (APAP group)...
October 2016: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28011363/significant-changes-in-the-photo-reactivity-of-tio2-in-the-presence-of-a-capped-natural-dissolved-organic-matter-layer
#13
Hong Peng, Yuan Chen, Lu Mao, Xu Zhang
Natural dissolved organic matter (NDOM) in surface waters has a high sorption affinity for TiO2 during long contact. An attached NDOM layer can act as a conduction band electron and/or valance band hole acceptor, and NDOM can also decrease the concentration of hydroxyl radicals (OH) in the bulk phase. Therefore, the degradation kinetics and mechanism for degradation of acetaminophen on NDOM capped TiO2 (NDOM-TiO2) are significantly different from those on raw TiO2. Quantum calculation results suggest that hydroxylation to the ortho position in relation to the acetamide group is more favorable...
December 18, 2016: Water Research
https://www.readbyqxmd.com/read/28006746/acetaminophen-induced-hepatotoxicity-preventive-effect-of-trans-anethole
#14
Bruno Ambrósio da Rocha, Alessandra M Versuti Ritter, Franciele Queiroz Ames, Odinei Hess Gonçalves, Fernanda Vitória Leimann, Lívia Bracht, Maria Raquel Marçal Natali, Roberto Kenji Nakamura Cuman, Ciomar Ap Bersani-Amado
The hepatotoxicity induced by APAP is caused by the excessive production of N-acetyl-para-benzoquinone imine (NAPQI), which, when reacting with hepatic proteins proved to cause irreversible lesions. Associated with this process, an intense inflammatory process is also evidenced, characterized by the increased cell influx and production/release of inflammatory mediators. Trans anethole, an aromatic compounds has been showed anti-inflammatory efficacy by inhibit the cellular recruitment and synthesis/releases of many proinflammatory mediators such as prostaglandin (PGE2), cytokines (TNF, IL-1) and nitrico oxide (NO)...
December 19, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27998381/who-needs-oxygen-with-positive-airway-pressure-therapy
#15
Susmita Chowdhuri, Abdulghani Sankari, James A Rowley
The diagnosis and management of obstructive sleep apnea (OSA) are increasingly being performed in the home. In the home management pathway, patients with high pretest probability for OSA are first tested using home sleep apnea testing and if positive for OSA, are treated with automatic positive airway pressure (APAP). The home management pathway has been validated by multiple investigators1-3 and is considered an alternative pathway in guidelines for the evaluation and management of OSA.4 However, there are limitations to the routine use of this pathway...
December 16, 2016: Journal of Clinical Sleep Medicine: JCSM: Official Publication of the American Academy of Sleep Medicine
https://www.readbyqxmd.com/read/27991908/early-activated-hepatic-stellate-cell-derived-paracrine-molecules-modulate-acute-liver-injury-and-regeneration
#16
Wenju Chang, Lujun Song, Xiujuan Chang, Meiling Ji, Hongshan Wang, Xinyu Qin, Weixin Niu
The effects of paracrine action from early activated hepatic stellate cells (HSCs) on resident liver epithelium cells are not clear. Here, we investigated whether a systemic infusion of early activated HSC-derived paracrine factors (HSC-CM) would evoke an enhanced liver protective response in acetaminophen (APAP)-induced acute liver injury (ALI) in mice and explored the possible underlying mechanisms. The survival rate, liver injury, and liver regeneration were analyzed in mice with or without HSC-CM treatment in vivo...
December 19, 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/27989599/lycopene-inhibits-reactive-oxygen-species-production-in-sk-hep-1%C3%A2-cells-and-attenuates-acetaminophen-induced-liver-injury-in-c57bl-6-mice
#17
Ana Carla Balthar Bandeira, Talita Prato da Silva, Glaucy Rodrigues de Araujo, Carolina Morais Araujo, Rafaella Cecília da Silva, Wanderson Geraldo Lima, Frank Silva Bezerra, Daniela Caldeira Costa
Our aim was to investigate the antioxidant potential of lycopene in different experimental liver models: in vitro, to evaluate the influence of lycopene on reactive oxygen species (ROS) production mediated by the PKC pathway and in vivo, to evaluate the protective effects of lycopene in an experimental model of hepatotoxicity. The in vitro study assessed the lycopene antioxidant potential by the quantification of ROS production in SK-Hep-1 cells unstimulated or stimulated by an activator of the PKC pathway...
December 15, 2016: Chemico-biological Interactions
https://www.readbyqxmd.com/read/27978773/a-longitudinal-assessment-of-mir-122-and-gldh-as-biomarkers-of-drug-induced-liver-injury-in-the-rat
#18
Petra Thulin, Robert J Hornby, Mariona Auli, Gunnar Nordahl, Daniel J Antoine, Philip Starkey Lewis, Christopher E Goldring, B Kevin Park, Neus Prats, Björn Glinghammar, Ina Schuppe-Koistinen
CONTEXT: There is an ongoing search for specific and translational biomarkers of drug-induced liver injury (DILI). MicroRNA-122 (miR-122) has previously shown potential as a sensitive, specific, and translational biomarker of DILI in both rodent, and human studies. OBJECTIVE: To build on previous work within the field, we examined biomarker kinetics in a rat model of acetaminophen (APAP)-induced liver injury to confirm the sensitivity, and specificity of miR-122 and glutamate dehydrogenase (GLDH)...
December 15, 2016: Biomarkers: Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals
https://www.readbyqxmd.com/read/27965156/fibri-nogen-drives-repair-after-acetaminophen-induced-liver-injury-via-leukocyte-%C3%AE-m%C3%AE-2-integrin-dependent-upregulation-of-mmp12
#19
Anna K Kopec, Nikita Joshi, Holly Cline-Fedewa, Anna V Wojcicki, Jessica L Ray, Bradley P Sullivan, John E Froehlich, Brendan F Johnson, Matthew J Flick, James P Luyendyk
BACKGROUND & AIMS: Acetaminophen (APAP)-induced liver injury is coupled to activation of the blood coagulation cascade and fibrin(ogen) accumulation within APAP-injured livers of experimental mice. We sought to define the precise role of fibrin(ogen) deposition in APAP-induced liver injury and repair METHODS: Fasted mice were injected with 300 mg/kg APAP i.p. and evaluated various times later RESULTS: In wild-type mice APAP overdose increased intrahepatic levels of high molecular weight cross-linked fibrin(ogen)...
December 10, 2016: Journal of Hepatology
https://www.readbyqxmd.com/read/27960556/acetaminophen-toxicity-in-rat-and-mouse-hepatocytes-in-vitro
#20
Otto Kučera, René Endlicher, David Rychtrmoc, Halka Lotková, Ondřej Sobotka, Zuzana Červinková
CONTEXT: Acetaminophen (APAP) hepatotoxicity is often studied in primary cultures of hepatocytes of various species, but there are only few works comparing interspecies differences in susceptibility of hepatocytes to APAP in vitro. OBJECTIVES: The aim of our work was to compare hepatotoxicity of APAP in rat and mouse hepatocytes in primary cultures. MATERIALS AND METHODS: Hepatocytes isolated from male Wistar rats and C57Bl/6J mice were exposed to APAP for up to 24 h...
December 14, 2016: Drug and Chemical Toxicology
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