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https://www.readbyqxmd.com/read/27931808/evaluation-of-a-single-dose-pigret-assay-for-acetaminophen-in-rats-compared-with-the-rbc-pig-a-assay
#1
Yuta Suzuki, Ken Goto, Yoshihiro Nakayama, Masatoshi Saratani, Takuya Takata, Takezo Okamoto, Shuzo Okazaki
As a part of a collaborative study of the Pig-a assay by the Mammalian Mutagenicity Study Group of the Japanese Environmental Mutagen Society, a genotoxicity study on acetaminophen (APAP) was performed using the red blood cell (RBC) Pig-a and PIGRET assays. The dose levels were set at 0 (vehicle, 0.5% methylcellulose solution), 500, 1000, and 2000mg/kg, and APAP was administered once by oral gavage to male Sprague Dawley rats. For the positive control group, N-nitroso-N-ethylurea (ENU, 40mg/kg) was administered in the same way...
November 15, 2016: Mutation Research
https://www.readbyqxmd.com/read/27929709/safety-of-buprenorphine-transdermal-system-in-the-management-of-pain-in-older-adults
#2
Joseph V Pergolizzi, Robert B Raffa, Zachary Marcum, Salvatore Colucci, Steven R Ripa
OBJECTIVES: To evaluate whether buprenorphine transdermal system (BTDS; Butrans®) is an option for the treatment of chronic pain in older adults. METHODS: This retrospective analysis of 16 placebo- and active-controlled and uncontrolled studies (N=6566) evaluated the safety and tolerability profile in patients exposed to BTDS and compared the safety profiles associated with BTDS treatment in older patients ≥ 65 years of age (65 to 98 years) and younger patients < 65 years of age (18 to 64 years)...
December 8, 2016: Postgraduate Medicine
https://www.readbyqxmd.com/read/27900802/therapeutic-potential-of-carfilzomib-an-irreversible-proteasome-inhibitor-against-acetaminophen-induced-hepatotoxicity-in-mice
#3
Abdulrazaq Alanazi, Saleh G Algfeley, Khaled A Al-Hosaini, Hesham M Korashy, Faisal Imam, Mahmoud N Nagi
Overdose of acetaminophen (APAP) is often associated with hepatotoxicity. Carfilzomib (CFZ) shows multiple pharmacological activities including anti-inflammatory potential. Therefore, this study was undertaken to evaluate the possible therapeutic effects of CFZ against APAP-induced hepatotoxicity. Hepatotoxicity was induced by administration of APAP (350 mg/kg, intraperitoneal). Mice were given CFZ (0.125, 0.25, or 0.5 mg/kg, intraperitoneal) 1.5 h after APAP administration. Animals were sacrificed on 6 h and blood and liver tissue samples were collected for analysis...
November 30, 2016: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/27891510/tropisetron-protects-against-acetaminophen-induced-liver-injury-via-suppressing-hepatic-oxidative-stress-and-modulating-the-activation-of-jnk-erk-mapk-pathways
#4
Fu-Chao Liu, Hung-Chen Lee, Chia-Chih Liao, Allen H Li, Huang-Ping Yu
Objectives. To investigate the protective effects of tropisetron on acetaminophen- (APAP-) induced liver injury in a mice model. Methods. C57BL/6 male mice were given tropisetron (0.3 to 10 mg/kg) 30 minutes before a hepatotoxic dose of acetaminophen (300 mg/kg) intraperitoneally. Twenty hours after APAP intoxication, sera alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, hepatic myeloperoxidase (MPO), malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) activities, and liver histopathological changes were examined...
2016: BioMed Research International
https://www.readbyqxmd.com/read/27886581/a-multi-omic-approach-to-elucidate-low-dose-effects-of-xenobiotics-in-zebrafish-danio-rerio-larvae
#5
Susie S Y Huang, Jonathan P Benskin, Nik Veldhoen, Bharat Chandramouli, Heather Butler, Caren C Helbing, John R Cosgrove
Regulatory-approved toxicity assays such as the OECD Fish Embryo Toxicity Assay (TG236) allow correlation of chemical exposure to adverse morphological phenotypes. However, these assays are ineffective in assessing sub-lethal (i.e. low-dose) effects, or differentiating between similar phenotypes induced by different chemicals. Inclusion of multi-omic analyses in studies investigating xenobiotic action provides improved characterization of biological response, thereby enhancing prediction of toxicological outcomes in whole animals in the absence of morphological effects...
November 18, 2016: Aquatic Toxicology
https://www.readbyqxmd.com/read/27872357/antipyretic-efficacy-and-safety-of-ibuprofen-versus-acetaminophen-suspension-in-febrile-children-results-of-2-randomized-double-blind-single-dose-studies
#6
Shyamalie Jayawardena, David Kellstein
Two blinded single-dose studies randomized children 6 months to 11 years old with fever to receive ibuprofen (IBU) pediatric suspension 7.5 mg/kg or acetaminophen (APAP) suspension 10 to 15 mg/kg. The primary efficacy parameter was time-weighted sum of temperature differences (TWSTD) from baseline through 8 hours for each study. Secondary end points included TWSTD from baseline through 6 hours, time to onset and duration of temperature control, and proportion with temperature control. Studies were pooled for post hoc analyses of efficacy and adverse event end points...
November 20, 2016: Clinical Pediatrics
https://www.readbyqxmd.com/read/27866976/protective-effect-of-rosiglitazone-against-acetaminophen-induced-acute-liver-injury-is-associated-with-down-regulation-of-hepatic-nadph-oxidases
#7
Jun-Xian Wang, Cheng Zhang, Lin Fu, Da-Gang Zhang, Bi-Wei Wang, Zhi-Hui Zhang, Yuan-Hua Chen, Yan Lu, Xi Chen, De-Xiang Xu
The peroxisome proliferator-activated receptor gamma (PPAR-γ) is a ligand-activated nuclear receptor that regulates glucose and lipid metabolism. The aim of the present study was to investigate the effects of rosiglitazone (RSG), a synthetic PPAR-γ agonist, on acetaminophen (APAP)-induced acute liver injury. Male CD-1 mice were injected with APAP (300mg/kg). Some mice were pretreated with RSG (20mg/kg) 48, 24 and 1h before APAP injection. As expected, RSG pretreatment alleviated APAP-induced acute liver injury...
November 17, 2016: Toxicology Letters
https://www.readbyqxmd.com/read/27863795/decomposition-of-acetaminophen-in-water-by-a-gas-phase-dielectric-barrier-discharge-plasma-combined-with-tio2-rgo-nanocomposite-mechanism-and-degradation-pathway
#8
Guyu Zhang, Yabing Sun, Chunxiao Zhang, Zhongqing Yu
Acetaminophen (APAP) served as the model pollutant to evaluate the feasibility of pollutant removal by gas phase dielectric barrier discharge plasma combined with the titanium dioxide-reduced Graphene Oxide (TiO2-rGO) nanocomposite. TiO2-rGO nanocomposite was prepared using the modified hydrothermal method and characterized by TEM and XPS before and after plasma process. The results indicated that the APAP degradation efficiency was significantly improved to 92% after 18min of discharge plasma treatment coupling 0...
February 5, 2017: Journal of Hazardous Materials
https://www.readbyqxmd.com/read/27862262/different-effects-of-selective-%C3%AE-1-adrenoceptor-antagonists-nebivolol-or-atenolol-in-acetaminophen-induced-heptatotoxicity-of-rats
#9
Remon R Rofaeil, Maha Yehia Kamel, Walaa Yehia Abdelzaher
Acetaminophen (APAP) overdose is a common cause of acute liver failure and beta blockers are commonly used drugs in clinical practice. This study aims to evaluate the effect of two different beta blockers agents as nebivolol and atenolol against APAP-induced hepatotoxicity. Male wistar rats were treated with APAP (2 g/kg/day, p.o.) to induce hepatotoxicity. Our results showed that nebivolol and atenolol reduced heart rate and blood pressure. Nebivolol (5 mg/kg /day, p.o.) for 14 days has a hepatoprotective effect shown by significant decrease in hepatic injury parameters (serum AST and ALT) with significant suppression of hepatic malondialdehyde (MDA) and nitric oxide (NO) which were elevated with APAP administration...
November 14, 2016: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/27862231/early-stage-functions-of-mitochondrial-autophagy-and-oxidative-stress-in-acetaminophen-induced-liver-injury
#10
Yan Gao, Shifeng Chu, Zhao Zhang, Wei Zuo, Congyuan Xia, Qidi Ai, Piao Luo, Peng Cao, Naihong Chen
Mitochondria go through frequent cycles of fusion and fission, a process required for mitochondrial quality control by eliminating ROS-damaged mitochondria through mitochondrial autophagy. Acetaminophen (APAP) overdose can cause liver injury in animals and human beings by inducing mitochondrial damage, which need to be further evaluated. The aim of the current study is to assess the changes between oxidative damage and mitophagy in vivo and in vitro, which mimics APAP-induced liver injury (AILI) in humans. Liver damage was monitored by measuring the levels of biochemical indexes...
November 9, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27859489/elevated-fabp1-serum-levels-are-associated-with-poorer-survival-in-acetaminophen-induced-acute-liver-failure
#11
Constantine J Karvellas, Jaime L Speiser, Mélanie Tremblay, William M Lee, Christopher F Rose
BACKGROUND/AIM: Acetaminophen (APAP)-induced Acute Liver Failure (ALF) is associated with significant mortality. Traditional prognostic scores lack sensitivity. HYPOTHESIS: Serum Liver-type Fatty Acid Binding Protein (FABP1) early (day 1) or late (day 3-5) levels are associated with 21-day mortality in the absence of liver transplant. METHODS: Serum samples from 198 APAP-ALF patients (nested case control study with 99 survivors, 99 non-survivors) were analyzed by ELISA methods and assessed with clinical data from the US Acute Liver Failure Study Group (ALFSG) Registry (1998-2014)...
November 18, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27855209/baicalin-attenuates-il-17-mediated-acetaminophen-induced-liver-injury-in-a-mouse-model
#12
Chia-Chih Liao, Yuan-Ji Day, Hung-Chen Lee, Jiin-Tarng Liou, An-Hsun Chou, Fu-Chao Liu
BACKGROUND: IL-17 has been shown to be involved in liver inflammatory disorders in both mice and humans. Baicalin (BA), a major compound extracted from traditional herb medicine (Scutellariae radix), has potent hepatoprotective properties. Previous study showed that BA inhibits IL-17-mediated lymphocyte adhesion and downregulates joint inflammation. The aim of this study is to investigate the role of IL-17 in the hepatoprotective effects of BA in an acetaminophen (APAP)-induced liver injury mouse model...
2016: PloS One
https://www.readbyqxmd.com/read/27846064/serum-acetaminophen-protein-adduct-concentrations-in-pediatric-emergency-department-patients
#13
Kennon Heard, Victoria Anderson, Richard C Dart, Deidre Kile, Eric Lavonas, Jody L Green
: Acetaminophen toxicity is a common cause of pediatric liver failure. The diagnosis may be limited by the short window of detection of acetaminophen in serum. Recently acetaminophen protein adducts (APAP-CYS) have been used as a biomarker with a longer duration of detection. The objective of this study was to describe the serum concentrations of APAP-CYS in pediatric patients with and without reported therapeutic acetaminophen exposure. METHODS: A cross sectional study of children age 1 to <12 years presenting to a pediatric emergency department...
November 14, 2016: Journal of Pediatric Gastroenterology and Nutrition
https://www.readbyqxmd.com/read/27836781/nrf2-mediated-liver-protection-by-esculentoside-a-against-acetaminophen-toxicity-through-the-ampk-akt-gsk3%C3%AE-pathway
#14
Lidong Wang, Songling Zhang, Hang Cheng, Hongming Lv, Genhong Cheng, Xinxin Ci
Acetaminophen (APAP) overdose accounts for the majority of acute liver failure cases, and oxidative stress plays a key role in its toxic effects. Esculentoside A (EsA) has anti-oxidant activities, but its therapeutic potential for APAP hepatotoxicity remains unknown. This study aimed to assess the protective effects and mechanism of EsA against APAP-induced hepatotoxicity in vitro and in vivo. In vitro, EsA treatment inhibited APAP- or H2O2-induced cytotoxicity, H2O2 and O2(-) production, glutathione (GSH) depletion and apoptosis dependent on nuclear factor erythroid-2-related factor 2 (Nrf2) activation in HepG2 cells...
November 9, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27830448/estimating-the-effect-of-intravenous-acetaminophen-for-postoperative-pain-management-on-length-of-stay-and-inpatient-hospital-costs
#15
E Eve Shaffer, An Pham, Robert L Woldman, Andrew Spiegelman, Scott A Strassels, George J Wan, Thomas Zimmerman
INTRODUCTION: The provision of safe, effective, cost-efficient perioperative inpatient acute pain management is an important concern among clinicians and administrators within healthcare institutions. Overreliance on opioid monotherapy in this setting continues to present health risks for patients and increase healthcare costs resulting from preventable adverse events. The goal of this study was to model length of stay (LOS), potential opioid-related complications, and costs for patients reducing opioid use and adding intravenous acetaminophen (IV APAP) for management of postoperative pain...
November 9, 2016: Advances in Therapy
https://www.readbyqxmd.com/read/27830028/characterization-of-acetaminophen-induced-cytotoxicity-in-target-tissues
#16
Chao Guo, Guojie Xie, Min Su, Xinmou Wu, Xiuli Lu, Ka Wu, Chaohe Wei
Acetaminophen (APAP), commonly used in clinical prescription, has time- and dose-dependent side effects. Thus, further animal study warrants to be investigated to assess possible adverse effect of APAP application. Here, we conducted pre-clinical research to elucidate the molecular mechanism regarding APAP-mediated toxicological action. Our data showed that serous/urinary and hepatic/renal APAP concentrations were significantly increased when compared with normal control, which the liver tissue showed the highest level...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27830004/ferulic-acid-attenuated-acetaminophen-induced-hepatotoxicity-though-down-regulating-the-cytochrome-p-2e1-and-inhibiting-toll-like-receptor-4-signaling-mediated-inflammation-in-mice
#17
Junhui Yuan, Kuang Ge, Junhuan Mu, Jiang Rong, Li Zhang, Bin Wang, Jingyuan Wan, Gong Xia
Ferulic acid (FA), a phenolic acid which is abundant in vegetables and fruits, has been reported to exert anti-oxidative and anti-inflammatory activities. In the present study, the pharmacological effects and the underlying mechanisms of FA in mice with acetaminophen-induced hepatotoxicity were investigated. Our results revealed that FA pretreatment inhibited the augments of serum aminotransferases in a dose-dependent manner and attenuated the hepatic histopathological abnormalities and hepatocellular apoptosis in acetaminophen (APAP) exposed mice...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27818923/two-new-phenylpropanoid-glycosides-from-the-aerial-parts-of-lespedeza-cuneata
#18
Chuangfeng Zhang, Jian Zhou, Jingzhi Yang, Chuangjun Li, Jie Ma, Dan Zhang, Dongming Zhang
Two new phenylpropanoid glycosides named cuneataside E (1) and cuneataside F (2), were isolated from the aerial parts of Lespedeza cuneata (Dum. Cours.) G. Don, whose structures were E and Z isomer, respectively. Their structures were elucidated on the basis of comprehensive spectroscopic analysis (UV, IR, HR-ESI-MS, 1D and 2D NMR). In in vitro bioassays at 10 μmol/L, compound 1 showed moderate hepatoprotective activity against N-acetyl-p-aminophenol (APAP)-induced toxicity in HeG2 cells.
November 2016: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/27812602/a-non-hepatotropic-parasite-infection-increases-mortality-in-the-acetaminophen-induced-acute-liver-failure-murine-model-possible-roles-for-il-5-and-il-6
#19
Marco A De León-Nava, Carolina Álvarez-Delgado, Luis Donis-Maturano, Joselin Hernández-Ruiz, Aaron N Manjarrez-Reyna, Edgar Cruz-Avilés, Sonia Leon-Cabrera, Jorge Morales-Montor, José M Fragoso, Galileo Escobedo
We evaluated the effects of a non-hepatotropic parasite infection (Taenia crassiceps) on the outcome of acetaminophen-induced acute liver failure in mice. Uninfected and T. crassiceps infected mice orally received either 300 mg/kg acetaminophen or water as vehicle (n = 5 per group). Survival analysis, hepatocyte necrosis, alanine aminotransferase (ALT) levels, CYP2E1 protein, interleukin (IL-) 5, and IL-6 were assessed for all groups. All infected mice died within 16 h after exposure to acetaminophen (Tc+APAP group), whereas only one-third of uninfected animals exposed to acetaminophen (APAP group) died...
October 31, 2016: Memórias do Instituto Oswaldo Cruz
https://www.readbyqxmd.com/read/27792836/randomized-controlled-multicenter-clinical-trial-of-the-antipyretic-effect-of-intravenous-paracetamol-in-patients-admitted-to-hospital-with-infection
#20
Thomas Tsaganos, Ioulia K Tseti, Nikolaos Tziolos, Georgios-Stefanos Soumelas, Marina Koupetori, Athina Pyrpasopoulou, Karolina Akinosoglou, Charalambos Gogos, Nikolaos Tsokos, Asterios Karagiannis, Styliani Sympardi, Evangelos J Giamarellos-Bourboulis
AIM: No randomized study has been conducted for intravenous paracetamol (acetaminophen, APAP) for fever management due to infection. This is a study for a new ready-made infusion of paracetamol. METHODS: 80 patients with body temperature onset the last 24 hours greater than or equal to 38.5 °C due to infection were randomized to single administration of placebo (n = 39) or 1 g paracetamol (n = 41); temperature was recorded at standard intervals. Rescue medication with 1 g paracetamol was allowed...
October 28, 2016: British Journal of Clinical Pharmacology
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