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https://www.readbyqxmd.com/read/29761172/loss-of-hypoxia-inducible-factor-1%C3%AE-aggravates-%C3%AE-%C3%AE-t-cell-mediated-inflammation-during-acetaminophen-induced-liver-injury
#1
Tomohiro Suzuki, Shoko Minagawa, Takashi Yamazaki, Takatomo Arai, Mai Kanai, Satoko Shinjo, Nobuhito Goda
Acetaminophen (APAP)-induced liver injury is closely associated with acute hepatic inflammation. Hypoxia-inducible factor-1 (HIF-1) is activated during immunological processes and regulates gene expressions in various types of immune cells. Although HIF-1 controls the differentiation and functions of conventional T cells in chronic inflammation, the pathological importance of HIF-1 in innate-like T cells during acute inflammation remains unknown. Here, we investigated the role of HIF-1 in innate-like γδ T cells during APAP-induced acute liver injury...
May 2018: Hepatology Communications
https://www.readbyqxmd.com/read/29756216/bioavailability-of-suppository-acetaminophen-in-healthy-and-hospitalized-ill-dogs
#2
E R Sikina, J F Bach, Z Lin, R Gehring, B KuKanich
To determine the plasma pharmacokinetics of suppository acetaminophen (APAP) in healthy dogs and clinically ill dogs. This prospective study used six healthy client-owned and 20 clinically ill hospitalized dogs. The healthy dogs were randomized by coin flip to receive APAP orally or as a suppository in crossover study design. Blood samples were collected up to 10 hr after APAP dosing. The hospitalized dogs were administered APAP as a suppository, and blood collected at 2 and 6 hr after dosing. Plasma samples were analyzed by ultra-performance liquid chromatography with triple quadrupole mass spectrometry...
May 13, 2018: Journal of Veterinary Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29753208/mechanisms-of-acetaminophen-induced-liver-injury-and-its-implications-for-therapeutic-interventions
#3
REVIEW
Mingzhu Yan, Yazhen Huo, Shutao Yin, Hongbo Hu
Acetaminophen (APAP) overdose is the leading cause of drug-induced acute liver failure in many developed countries. Mitochondrial oxidative stress is considered to be the predominant cellular event in APAP-induced liver injury. Accordingly, N-acetyl cysteine, a known scavenger of reactive oxygen species (ROS), is recommended as an effective clinical antidote against APAP-induced acute liver injury (AILI) when it is given at an early phase; however, the narrow therapeutic window limits its use. Hence, the development of novel therapeutic approaches that can offer broadly protective effects against AILI is clearly needed...
April 22, 2018: Redox Biology
https://www.readbyqxmd.com/read/29748533/p53-attenuates-acetaminophen-induced-hepatotoxicity-by-regulating-drug-metabolizing-enzymes-and-transporter-expression
#4
Jiahong Sun, Yajie Wen, Yanying Zhou, Yiming Jiang, Yixin Chen, Huizheng Zhang, Lihuan Guan, Xinpeng Yao, Min Huang, Huichang Bi
Acetaminophen (APAP) overdose is the most frequent cause of drug-induced acute liver failure. Inhibition of APAP metabolic activation and promotion in APAP disposition are important to protect against APAP-induced liver injury. Tumor suppressor p53 is traditionally recognized as a surveillance molecule to preserve genome integrity. Recent studies have emerged on discovering its functions in metabolic regulation. Our previous study reported that p53 promoted bile acid disposition and alleviated cholestastic syndrome...
May 10, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29739258/4-methylpyrazole-protects-against-acetaminophen-hepatotoxicity-in-mice-and-in-primary-human-hepatocytes
#5
J Y Akakpo, A Ramachandran, S E Kandel, H M Ni, S C Kumer, B H Rumack, H Jaeschke
Liver injury due to acetaminophen (APAP) overdose is the major cause of acute liver failure in the United States. While treatment with N-acetylcysteine is the current standard of care for APAP overdose, anecdotal evidence suggests that administration of 4-methylpyrazole (4MP) may be beneficial in the clinic. The objective of the current study was to examine the protective effect of 4MP and its mechanism of action. Male C57BL/6J mice were co-treated with 300 mg/kg of APAP and 50 mg/kg of 4MP. The severe liver injury induced by APAP at 6 h as indicated by elevated plasma alanine aminotransferase activities, centrilobular necrosis, and nuclear DNA fragmentation was almost completely eliminated by 4MP...
January 1, 2018: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/29735980/metabolic-modulation-of-acetaminophen-induced-hepatotoxicity-by-osteopontin
#6
Yankai Wen, Chenchen Wang, Jinyang Gu, Chang Yu, Kaixia Wang, Xuehua Sun, Yun Sun, Hailong Wu, Ying Tong, Qiang Xia, Xiaoni Kong
Induction of osteopontin (OPN), a well-known pro-inflammatory molecule, has been observed in acetaminophen (APAP)-induced hepatotoxicity. However, the precise cell source for OPN induction and its role during APAP-induced hepatotoxicity has not been fully explored. By employing a hepatotoxic mouse model induced by APAP overdose, we demonstrate that both serum and hepatic OPN levels were significantly elevated in response to APAP treatment. Our in vivo and in vitro studies clearly indicated that the induced expression of hepatic OPN was mainly located in necrosis areas and produced by dying or dead hepatocytes...
May 7, 2018: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/29734456/intravenous-acetaminophen-may-be-associated-with-reduced-odds-of-30-day-readmission-after-total-knee-arthroplasty
#7
Michael A Mont, Belinda Lovelace, An T Pham, Ryan N Hansen, Morad Chughtai, Chukwuweike U Gwam, Anton Khlopas, John W Barrington
The purpose of this study was (1) to evaluate 30-day readmission rates in total knee arthroplasty (TKA) patients who either received intravenous (IV) or oral (PO) acetaminophen (APAP) perioperatively and (2) to extrapolate the potential annual cost savings on the national level. This was a review of 190,691 TKA recipients between the years 2012 and 2015 who received either IV ( n  = 56,475) or PO APAP ( n  = 134,216). All-cause readmissions that occurred between patient discharge and 30 days postdischarge were recorded...
May 7, 2018: Journal of Knee Surgery
https://www.readbyqxmd.com/read/29730296/fgf21-mediates-the-protective-effect-of-fenofibrate-against-acetaminophen-induced-hepatotoxicity-via-activating-autophagy-in-mice
#8
Yi Zhang, Yingying Pan, Rongrong Xiong, Jujia Zheng, Qianyao Li, Saisai Zhang, Xiaokun Li, Xuebo Pan, Shulin Yang
Overdose of acetaminophen (APAP) induces acute liver injury due in part to destruction of mitochondria and resulted oxidative stress. Recently, FGF21 has been demonstrated to be an endocrine factor to protect liver from oxidative stress. The aim of present study is to explore the role of fibroblast growth factor 21 (FGF21) in the protective effect of fenofibrate, an agonist of peroxisome proliferator-activated receptor alpha (PPARα), against acetaminophen (APAP)-induced liver injury. Mice and primary cultured hepatocytes were used to test the potential hepatoprotective effect of fenofibrate against APAP-induced hepatotoxicity...
May 3, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29729197/excessive-plasmin-compromises-hepatic-sinusoidal-vascular-integrity-after-acetaminophen-overdose
#9
Siqi Gao, Robert Silasi-Mansat, Mandi Behar, Florea Lupu, Courtney T Griffin
The serine protease plasmin degrades extracellular matrix (ECM) components both directly and indirectly through activation of matrix metalloproteinases. Excessive plasmin activity and subsequent ECM degradation causes hepatic sinusoidal fragility and hemorrhage in developing embryos. We report here that excessive plasmin activity in a murine acetaminophen (APAP) overdose model likewise compromises hepatic sinusoidal vascular integrity in adult animals. We found that hepatic plasmin activity is upregulated significantly at 6 hr after APAP overdose...
May 5, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29719809/autoimmune-pulmonary-alveolar-proteinosis-in-an-adolescent-successfully-treated-with-inhaled-rhgm-csf-molgramostim
#10
Marta E Gajewska, Sajitha S Sritharan, Eric Santoni-Rugiu, Elisabeth M Bendstrup
Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare parenchymal lung disease characterized by accumulation of surfactant in the airways with high levels of granulocyte-macrophage colony stimulating factor (GM-CSF) antibodies in blood. Disease leads to hypoxemic respiratory failure. Whole lung lavage (WLL) is considered the first line therapy, but procedure can be quite demanding, specifically for children. Recently alternative treatment options with inhaled GM-CSF have been described but no consensus about the standard treatment exists...
2018: Respiratory Medicine Case Reports
https://www.readbyqxmd.com/read/29719159/cuscuta-arvensis-beyr-dodder-in-vivo-hepatoprotective-effects-against-acetaminophen-induced-hepatotoxicity-in-rats
#11
Ufuk Koca-Caliskan, Ismet Yilmaz, Asli Taslidere, Funda N Yalcin, Ceylan Aka, Nazim Sekeroglu
Cuscuta arvensis Beyr. is a parasitic plant, and commonly known as "dodder" in Europe, in the United States, and "tu si zi shu" in China. It is one of the preferred spices used in sweet and savory dishes. Also, it is used as a folk medicine for the treatment particularly of liver problems, knee pains, and physiological hepatitis, which occur notably in newborns and their mothers in the southeastern part of Turkey. The purpose of this study was to investigate the hepatoprotective effects and antioxidant activities of aqueous and methanolic extracts of C...
May 2, 2018: Journal of Medicinal Food
https://www.readbyqxmd.com/read/29713191/endoscopic-comparison-of-gastroduodenal-injury-with-over-the-counter-doses-of-new-fast-dissolving-ibuprofen-and-paracetamol-formulations-a-randomized-placebo-controlled-4-way-crossover-clinical-trial
#12
Frank L Lanza, Agron Collaku, Dongzhou J Liu
Background: While gastrointestinal (GI) effects of standard ibuprofen and N-acetyl-p-aminophenol (APAP) have been reported, upper GI injury following treatment with fast-dissolving (FD) formulations of these analgesics has not been investigated. We evaluated upper GI effects of over-the-counter doses of 2 FD ibuprofen products and 1 FD-APAP product. Methods: In a randomized, placebo-controlled, endoscopist-blinded, 4-way crossover study, 28 healthy subjects received FD ibuprofen 2×200 mg liquid capsules 3 times daily (TID), ibuprofen 2×200 mg tablets TID, FD-APAP 2×500 mg tablets 4 times daily (QID), and placebo 2×500 mg tablets QID for 7 days...
2018: Clinical and Experimental Gastroenterology
https://www.readbyqxmd.com/read/29707092/improved-outcomes-associated-with-the-use-of-intravenous-acetaminophen-for-management-of-acute-post-surgical-pain-in-cesarean-sections-and-hysterectomies
#13
Richard D Urman, Elaine A Boing, An T Pham, Victor Khangulov, Randi Fain, Brian H Nathanson, Xuan Zhang, George J Wan, Belinda Lovelace, Jessica Cirillo
Background: Post-surgical pain impacts many patient outcomes. Effective pain management increasingly relies on multimodal analgesia regimens in which acetaminophen (APAP) is a key component. The aim of our study was to examine the impact of oral APAP versus intravenous (IV) APAP as a component of post-surgical pain management after Cesarean sections and hysterectomies. Methods: A retrospective analysis of the Cerner HealthFacts® database (from January, 2011 to December, 2015) was conducted to compare outcomes of Cesarean section and hysterectomy surgery patients who received oral APAP to those who received IV APAP post-surgically...
June 2018: Journal of Clinical Medicine Research
https://www.readbyqxmd.com/read/29705271/effects-of-human-sult1a3-sult1a4-genetic-polymorphisms-on-the-sulfation-of-acetaminophen-and-opioid-drugs-by-the-cytosolic-sulfotransferase-sult1a3
#14
Ahsan F Bairam, Mohammed I Rasool, Fatemah A Alherz, Maryam S Abunnaja, Amal A El Daibani, Katsuhisa Kurogi, Ming-Cheh Liu
Sulfoconjugation has been shown to be critically involved in the metabolism of acetaminophen (APAP), morphine, tapentadol and O-desmethyl tramadol (O-DMT). The objective of this study was to investigate the effects of single nucleotide polymorphisms (SNPs) of human SULT1A3 and SULT1A4 genes on the sulfating activity of SULT1A3 allozymes toward these analgesic compounds. Twelve non-synonymous coding SNPs (cSNPs) of SULT1A3/SULT1A4 were investigated, and the corresponding cDNAs were generated by site-directed mutagenesis...
April 26, 2018: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29703389/association-of-antioxidant-nutraceuticals-and-acetaminophen-paracetamol-friend-or-foe
#15
REVIEW
Mohamed Abdel-Daim, Abdelrahman Ibrahim Abushouk, Raffaella Reggi, Nagendra Sastry Yarla, Maura Palmery, Ilaria Peluso
Acetaminophen (paracetamol or APAP) is an analgesic and antipyretic drug that can induce oxidative stress-mediated hepatotoxicity at high doses. Several studies reported that antioxidant nutraceuticals, in particular phenolic phytochemicals from dietary food, spices, herbs and algae have hepatoprotective effects. Others, however, suggested that they may negatively impact the metabolism, efficacy and toxicity of APAP. The aim of this review is to discuss the pros and cons of the association of antioxidant nutraceuticals and APAP by reviewing the in vivo evidence, with particular reference to APAP pharmacokinetics and hepatotoxicity...
April 2018: Journal of Food and Drug Analysis
https://www.readbyqxmd.com/read/29698721/fixed-but-not-autoadjusting-positive-airway-pressure-attenuates-the-time-dependent-decline-in-glomerular-filtration-rate-in-patients-with-obstructive-sleep-apnea
#16
Oreste Marrone, Fabio Cibella, Jean-Louis Pépin, Ludger Grote, Johan Verbraecken, Tarja Saaresranta, John A Kvamme, Ozen K Basoglu, Carolina Lombardi, Walter T McNicholas, Jan Hedner, Maria R Bonsignore
BACKGROUND: The impact of treating obstructive sleep apnea (OSA) on renal function decline is controversial. Previous studies usually included small samples and did not consider specific effects of different continuous positive airway pressure (CPAP) modalities. The aim of this study was to evaluate the respective influence of fixed and auto-adjusting CPAP modes on estimated glomerular filtration rate (eGFR) in a large sample of patients derived from the prospective European Sleep Apnea Database (ESADA) cohort...
April 23, 2018: Chest
https://www.readbyqxmd.com/read/29696019/high-mobility-group-box-1-induced-complement-activation-causes-sterile-inflammation
#17
Sook Young Kim, Myoungsun Son, Sang Eun Lee, In Ho Park, Man Sup Kwak, Myeonggil Han, Hyun Sook Lee, Eun Sook Kim, Jae-Young Kim, Jong Eun Lee, Ji Eun Choi, Betty Diamond, Jeon-Soo Shin
High-mobility group box 1 (HMGB1), a well-known danger-associated molecular pattern molecule, acts as a pro-inflammatory molecule when secreted by activated immune cells or released after necrotic cell damage. HMGB1 binds to immunogenic bacterial components and augments septic inflammation. In this study, we show how HMGB1 mediates complement activation, promoting sterile inflammation. We show that HMGB1 activates the classical pathway of complement system in an antibody-independent manner after binding to C1q...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29695229/rituximab-for-auto-immune-alveolar-proteinosis-a-real-life-cohort-study
#18
Berenice Soyez, Raphael Borie, Cedric Menard, Jacques Cadranel, Leonidas Chavez, Vincent Cottin, Emmanuel Gomez, Sylvain Marchand-Adam, Sylvie Leroy, Jean-Marc Naccache, Hilario Nunes, Martine Reynaud-Gaubert, Laurent Savale, Abdellatif Tazi, Lidwine Wemeau-Stervinou, Marie-Pierre Debray, Bruno Crestani
BACKGROUND: Whole lung lavage is the current standard therapy for pulmonary alveolar proteinosis (PAP) that is characterized by the alveolar accumulation of surfactant. Rituximab showed promising results in auto-immune PAP (aPAP) related to anti-GM-CSF antibody. METHODS: We aimed to assess efficacy of rituximab in aPAP in real life and all patients with aPAP in France that received rituximab were retrospectively analyzed. RESULTS: Thirteen patients were included...
April 25, 2018: Respiratory Research
https://www.readbyqxmd.com/read/29689524/influence-of-dom-components-salinity-ph-nitrate-and-bicarbonate-on-the-indirect-photodegradation-of-acetaminophen-in-simulated-coastal-waters
#19
Ying Bai, Zhengguo Cui, Rongguo Su, Keming Qu
The indirect photodegradation behaviors of acetaminophen (APAP) were investigated in the presence of four kinds of dissolved organic matter (DOM) and were also assessed in the presence of seawater components and conditions such as salinity, pH, nitrate and bicarbonate. The results showed three important findings: firstly, in the indirect photolysis of APAP, the contributions of 3 DOM*, ·OH and 1 O2 were >85.0%, 2.3-9.9% and 0.8-2.6% at pH 8.0. Secondly, DOM was divided into four terrestrial humic-like components by Excitation-emission matrix spectroscopy (EEMs) combined with parallel factor analysis (PARAFAC)...
April 18, 2018: Chemosphere
https://www.readbyqxmd.com/read/29689376/il-17-deficiency-attenuates-acetaminophen-induced-hepatotoxicity-in-mice
#20
Hung-Chen Lee, Chia-Chih Liao, Yuan-Ji Day, Jiin-Tarng Liou, Allen H Li, Fu-Chao Liu
Acetaminophen (APAP) overdose results in the production of reactive oxygen species (ROS), hepatocyte necrosis, and cell death, and leads to acute liver failure. Interleukin-17 (IL-17), a pro-inflammatory cytokine, plays a key role in the recruitment of neutrophils into sites of inflammation and subsequent damage after liver ischemia-reperfusion injury. In this study, we employed IL-17 knockout (KO) mice to investigate the role of IL-17 in APAP-induced hepatotoxicity. IL-17 wide type (WT) and IL-17 KO mice received an intraperitoneal injection of APAP (300 mg/kg)...
April 21, 2018: Toxicology Letters
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