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https://www.readbyqxmd.com/read/29136249/natural-polyphenol-chlorogenic-acid-protects-against-acetaminophen-induced-hepatotoxicity-by-activating-erk-nrf2-antioxidative-pathway
#1
Mengjuan Wei, Zhiyong Zheng, Liang Shi, Yao Jin, Lili Ji
Hepatotoxicity due to acetaminophen (APAP) overdose is a leading cause of drug-induced acute liver failure in clinic. Chlorogenic acid (CGA), a dietary polyphenol, was reported to prevent APAP-induced liver injury in our previous studies. This study aims to investigate the protection provided by CGA against APAP-induced hepatotoxicity via focusing on nuclear factor erythroid 2-related factor 2 (Nrf2) and extracellular regulated protein kinases (ERK)1/2. CGA prevented APAP-induced oxidative liver injury and enhanced Nrf2 activation in mice and in hepatocytes in vitro...
November 10, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29132223/comparison-of-the-relative-stability-of-pharmaceutical-cocrystals-consisting-of-paracetamol-and-dicarboxylic-acids
#2
Naoto Suzuki, Masatoshi Kawahata, Kentaro Yamaguchi, Toyofumi Suzuki, Kazuo Tomono, Toshiro Fukami
OBJECTIVE: The aim of this study is to evaluated evaluated the relative stability of pharmaceutical cocrystals consisting of paracetamol (APAP) and oxalic acid (OXA) or maleic acid (MLA). SIGNIFICANCE: These observations of cocrystal stability under various conditions are useful coformer criteria when cocrystals are selected as the API in drug development. METHOD: The relative stability was determined from the preferentially formed cocrystals under various conditions...
November 13, 2017: Drug Development and Industrial Pharmacy
https://www.readbyqxmd.com/read/29125562/a-new-nortriterpenoid-a-sesquiterpene-and-hepatoprotective-lignans-isolated-from-the-fruit-of-schisandra-chinensis
#3
Fenghua Li, Ting Zhang, Hua Sun, Haifeng Gu, Hongqing Wang, Xianming Su, Changkang Li, Baoming Li, Ruoyun Chen, Jie Kang
A new nortriterpenoid, 19(R)-hydroxyl-wuweizidilactone H (1), and a sesquiterpene, (6R)-β-chamigrenic acid (2), together with one known nortriterpenoid, wuweizidilactone H (3), and three known hepatoprotective lignans, micrantherin A (4), gomisin M₂ (5) and schizandrin (6) were isolated from the fruit of Schisandra chinensis. Their structures were elucidated by UV, IR, HRESIMS, NMR spectra and X-ray analysis. Among them, the absolute configuration of 2 was confirmed for the first time. In vitro assays, compounds 4-6 (10 μM) exhibited hepatoprotective activities (survival rate: 44%, 43% and 44%) against damage induced by N-acetyl-p-aminophenol (APAP) in human liver carcinoma (HepG2) cells...
November 10, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29120676/glutamine-protection-in-an-experimental-model-of-acetaminophen-nephrotoxicity
#4
Marco Brovedan, Sara María Molinas, Gerardo Pisani, Liliana Alicia Monasterolo, Laura Trumper
Acetaminophen (APAP) is a widely prescribed analgesic - antipyretic drug. In the present work we studied the effects of glutamine (Gln) in an "in vivo" model of APAP-induced nephrotoxicity in male Wistar rats. Renal function, histological characteristics and Na+, K+ ATPase cortical abundance and distribution were analyzed. The appearance of HSP70 and actin in urine were also evaluated. Mieloperoxidase activity in cortical tissue was measured as an index of the inflammatory response. Gln administration 30 min before APAP protected from the renal functional and histological damage promoted by APAP...
November 9, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/29108608/treatment-of-obstructive-sleep-apnea-choosing-the-best-positive-airway-pressure-device
#5
REVIEW
Neil Freedman
Positive airway pressure (PAP) remains primary therapy for most patients with obstructive sleep apnea (OSA). CPAP, APAP, and BPAP are all reasonable therapies that can be used for patients with uncomplicated OSA across the spectrum of disease severity. BPAP should be considered for patients who are nonadherent to CPAP or APAP therapy because of pressure intolerance. Several additional factors should be considered when choosing the type of PAP device for a given patient, including associated symptoms and comorbid medical problems, cost, access to online data management and patient portals, and the portability for the device for patients who travel frequently...
December 2017: Sleep Medicine Clinics
https://www.readbyqxmd.com/read/29107792/caffeine-and-acetaminophen-association-effects-on-mitochondrial-bioenergetics
#6
Débora F Gonçalves, Nelson R de Carvalho, Martim B Leite, Aline A Courtes, Diane D Hartmann, Sílvio T Stefanello, Ingrid K da Silva, Jéferson L Franco, Félix A A Soares, Cristiane L Dalla Corte
AIMS: Many studies have been demonstrating the role of mitochondrial function in acetaminophen (APAP) hepatotoxicity. Since APAP is commonly consumed with caffeine, this work evaluated the effects of the combination of APAP and caffeine on hepatic mitochondrial bioenergetic function in mice. MAIN METHODS: Mice were treated with caffeine (20mg/kg, intraperitoneal (i.p.)) or its vehicle and, after 30min, APAP (250mg/kg, i.p.) or its vehicle. Four hours later, livers were removed, and the parameters associated with mitochondrial function and oxidative stress were evaluated...
October 28, 2017: Life Sciences
https://www.readbyqxmd.com/read/29078257/therapeutic-dose-of-green-tea-extract-provokes-liver-damage-and-exacerbates-paracetamol-induced-hepatotoxicity-in-rats-through-oxidative-stress-and-caspase-3-dependent-apoptosis
#7
Hanan A El-Bakry, G El-Sherif, Rehab M Rostom
Green tea extract (GTE) is considered to be endowed with countless healthful properties. Nevertheless, data concerning the hepatoprotective activities of GTE and its utilization as a therapeutic intervention for paracetamol (APAP) overdose are conflicting and intriguing. The present study was undertaken to address the effect of therapeutic dose of GTE on the liver, evaluate the potential hepatoprotection of GTE against APAP-induced hepatotoxicity, asses the regenerative capacity of the liver after discontinuation of treatments, and explore the mechanisms underlying these effects...
October 17, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29067470/multiple-micrornas-function-as-self-protective-modules-in-acetaminophen-induced-hepatotoxicity-in-humans
#8
Dianke Yu, Leihong Wu, Pritmohinder Gill, William H Tolleson, Si Chen, Jinchun Sun, Bridgett Knox, Yaqiong Jin, Wenming Xiao, Huixiao Hong, Yong Wang, Zhen Ren, Lei Guo, Nan Mei, Yongli Guo, Xi Yang, Leming Shi, Yinting Chen, Linjuan Zeng, Kostiantyn Dreval, Volodymyr Tryndyak, Igor Pogribny, Hong Fang, Tieliu Shi, Sandra McCullough, Sudeepa Bhattacharyya, Laura Schnackenberg, William Mattes, Richard D Beger, Laura James, Weida Tong, Baitang Ning
Acetaminophen (APAP) overdose is the leading cause of acute liver failure. Yet the mechanisms underlying adaptive tolerance toward APAP-induced liver injury are not fully understood. To better understand molecular mechanisms contributing to adaptive tolerance to APAP is an underpinning foundation for APAP-related precision medicine. In the current study, the mRNA and microRNA (miRNA) expression profiles derived from next generation sequencing data for APAP-treated (5 and 10 mM) HepaRG cells and controls were analyzed systematically...
October 24, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/29056914/acetaminophen-induced-liver-injury-alters-the-acyl-ethanolamine-based-anti-inflammatory-signaling-system-in-liver
#9
Patricia Rivera, Antoni Pastor, Sergio Arrabal, Juan Decara, Antonio Vargas, Laura Sánchez-Marín, Francisco J Pavón, Antonia Serrano, Dolores Bautista, Anna Boronat, Rafael de la Torre, Elena Baixeras, M Isabel Lucena, Fernando R de Fonseca, Juan Suárez
Protective mechanisms against drug-induced liver injury are actively being searched to identify new therapeutic targets. Among them, the anti-inflammatory N-acyl ethanolamide (NAE)-peroxisome proliferators activated receptor alpha (PPARα) system has gained much interest after the identification of its protective role in steatohepatitis and liver fibrosis. An overdose of paracetamol (APAP), a commonly used analgesic/antipyretic drug, causes hepatotoxicity, and it is being used as a liver model. In the present study, we have analyzed the impact of APAP on the liver NAE-PPARα system...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29054140/acetaminophen-toxicity-novel-insights-into-mechanisms-and-future-perspectives
#10
Anup Ramachandran, Hartmut Jaeschke
Acetaminophen (APAP) overdose is the most common cause of acute liver failure in the United States and decades of intense study of its pathogenesis resulted in development of the antidote Nacetylcysteine, which facilitates scavenging of the reactive metabolite and is the only treatment in clinical use. However, the narrow therapeutic window of this intervention necessitates a better understanding of the intricacies of APAP-induced liver injury for development of additional therapeutic approaches which can benefit late presenting patients...
October 20, 2017: Gene Expression
https://www.readbyqxmd.com/read/29053632/protective-effect-of-flavonoids-from-ziziphus-jujuba-cv-jinsixiaozao-against-acetaminophen-induced-liver-injury-by-inhibiting-oxidative-stress-and-inflammation-in-mice
#11
Weizhen Huang, Yongjie Wang, Xiaoyan Jiang, Yueyue Sun, Zhongxi Zhao, Siying Li
This study was aimed to investigate the chemical composition, antioxidant activities and hepatoprotective effect of flavonoids from Ziziphus jujuba cv. Jinsixiaozao (ZJF). The composition of ZJF was analyzed by high performance liquid chromatography (HPLC) and Liquid chromatography-mass spectrometry (LC-MS), and antioxidant properties were investigated by biological assays in vitro. The hepatoprotective activity of ZJF was evaluated in acetaminophen (APAP)-treated BALB/c mice. Results indicate that ZJF displayed significant antioxidant capacity...
October 20, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29050482/the-effect-of-sulforaphane-on-oxidative-stress-and-inflammation-in-rats-with-toxic-hepatitis-induced-by-acetaminophene
#12
E Dokumacioglu, H Iskender, M S Aktas, B Hanedan, A Dokumacioglu, T M Sen, A Musmul
OBJECTIVE: The aim of the present study was to reveal the possible effect of sulforaphane on oxidative stress and inflammation in rats liver with toxic hepatitis induced by acetaminophene. BACKGROUND: Sulforaphane is a compound with high antioxidant properties. Acetaminophen, which is a para-aminophenol derivative, can lead to fatal hepatic necrosis with direct hepatotoxic effects at high doses. METHODS: Thirty six male Sprague-Dawley rats were randomly divided into four groups...
2017: Bratislavské Lekárske Listy
https://www.readbyqxmd.com/read/29050468/impact-of-polymer-type-and-relative-humidity-on-the-long-term-physical-stability-of-amorphous-solid-dispersions
#13
Kristin Lehmkemper, Samuel O Kyeremateng, Oliver Heinzerling, Matthias Degenhardt, Gabriele Sadowski
The purpose of this work is to compare the long-term physical stability of amorphous solid dispersion (ASD) formulations based on three different commercially used excipients, namely, poly(vinylpyrrolidone) K25 (PVP), poly(vinylpyrrolidone-co-vinyl acetate) (PVPVA64), and hydroxypropyl methylcellulose acetate succinate 126G (HPMCAS), at standardized ICH storage conditions, 25 °C/0% relative humidity (RH), 25 °C/60% RH, and 40 °C/75% RH. Acetaminophen (APAP) and naproxen (NAP) were used as active pharmaceutical ingredients (APIs)...
November 7, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29042982/expression-of-glutathione-s-transferase-a1-a-phase-ii-drug-metabolizing-enzyme-in-acute-hepatic-injury-on-mice
#14
Xin Ma, Fangping Liu, Minmin Li, Zhi Li, Yuexia Lin, Rui Li, Changwen Li, Yicong Chang, Changwei Zhao, Qing Han, Qiong Zhou, Yulin Zhao, Dening Wang, Jingli Liu
In the present study, three models of acute liver injury in mice were induced via the administration of CCl4 (35 mg/kg, 24 h), acetyl-para-aminophenol (APAP; 200 mg/kg, 12 h) and ethanol (14 ml/kg, 8 h) to study the effect of glutathione S-transferase A1 (GSTA1) on acute liver injury. The serum levels of alanine transaminase, aspartate transaminase and liver homogenate indicators (superoxide dismutase, glutathione and glutathione peroxidase) were significantly lower in model groups compared with the control group (P<0...
October 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29035890/biocharacterization-of-heat-shock-protein-90-in-acetaminophen-treated-livers-without-conspicuous-drug-induced-liver-injury
#15
Ka Wu, Chao Guo, Min Su, Xinmou Wu, Rong Li
BACKGROUND/AIMS: Acetaminophen (APAP) refers to a medication used to manage pain and fever symptoms. Heat shock protein 90 (Hsp90) is to be expressed during various stresses, such as wound healing and tissue remodeling. Recently, it is discovered that Hsp90 is a potential modifier of cytogenesis. In comparison to clinical references of liver damage, this study was designed to assess the potential bioeffect of Hsp90 in APAP-treated livers without conspicuous drug induced liver injury (DILI)...
October 16, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29032512/il-33-signalling-in-liver-immune-cells-enhances-drug-induced-liver-injury-and-inflammation
#16
Maísa Mota Antunes, Alan Moreira Araújo, Ariane Barros Diniz, Rafaela Vaz Sousa Pereira, Débora Moreira Alvarenga, Bruna Araújo David, Renata Monti Rocha, Maria Alice Freitas Lopes, Sarah Cozzer Marchesi, Brenda Naemi Nakagaki, Érika Carvalho, Pedro Elias Marques, Bernhard Ryffel, Valérie Quesniaux, Rodrigo Guabiraba Brito, José Carlos Alves Filho, Denise Carmona Cara, Rafael Machado Rezende, Gustavo Batista Menezes
OBJECTIVE AND DESIGN: The aim of this study was to investigate the contribution of IL-33/ST2 axis in the onset and progression of acute liver injury using a mice model of drug-induced liver injury (DILI). MATERIAL AND TREATMENTS: DILI was induced by overdose administration of acetaminophen (APAP) by oral gavage in wild-type BALB/c, ST2-deficient mice and in different bone marrow chimeras. Neutrophils were depleted by anti-Ly6G and macrophages with clodronate liposomes (CLL)...
October 14, 2017: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/29025138/relative-bioavailability-intranasal-abuse-potential-and-safety-of-benzhydrocodone-acetaminophen-compared-with-hydrocodone-bitartrate-acetaminophen-in-recreational-drug-abusers
#17
Sven M Guenther, Travis C Mickle, Andrew C Barrett, Kathryn Ann Roupe, Jing Zhou, Vincent Lam
Objectives: Benzhydrocodone is a hydrocodone prodrug that has been combined with acetaminophen (APAP) in a novel immediate-release analgesic. This study evaluated the relative bioavailability, intranasal abuse potential, and safety of benzhydrocodone/APAP compared with commercially available hydrocodone bitartrate (HB)/APAP. Design: Single-center, randomized, double-blind, double-dummy, two-part study comprising a Dose Selection (Part A) phase and a Main Study (Part B) phase...
August 25, 2017: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
https://www.readbyqxmd.com/read/29025005/correlation-of-pain-reduction-with-fmri-bold-response-in-osteoarthritis-patients-treated-with-paracetamol-randomized-double-blind-crossover-clinical-efficacy-study
#18
Yong Yue, Agron Collaku
Objective: To assess the relationship between the analgesic efficacy of extended-release paracetamol (ER-APAP) and brain blood oxygen level-dependent (BOLD) signal activation in response to painful stimulation measured by functional magnetic resonance imaging (fMRI) in patients with osteoarthritis of the knee. Methods: This placebo-controlled, double-blind, crossover, randomized trial (N = 25) comprised three treatment periods in which patients received four doses of an eight-hour ER-APAP caplet (2 x 665 mg), four doses of matched placebo, and no treatment...
August 29, 2017: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
https://www.readbyqxmd.com/read/29022574/osthole-prevents-acetaminophen-induced-liver-injury-in-mice
#19
Yun Cai, Wu Sun, Xin-Xin Zhang, Yan-Die Lin, Hao Chen, Hao Li
Acetaminophen (APAP) overdose leads to severe hepatotoxicity. Osthole, a natural coumarin found in traditional Chinese medicinal herbs, has therapeutic potential in the treatment of various diseases. In this study, we investigated the effects of osthole against APAP-induced hepatotoxicity in mice. Mice were administered osthole (100 mg·kg(-1)·d(-1), ip) for 3 d, then on the fourth day APAP (300 mg/kg, ip) was co-administered with osthole. The mice were euthanized post-APAP, their serum and livers were collected for analysis...
October 12, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28988613/amelioration-of-panadol-induced-nephrotoxicity-via-down-regulation-of-bax-bcl2-ratio-with-some-antioxidants
#20
Nouf Al-Rasheed, Laila M Faddah, Iman H Hasan, Hanaa M Ali, Nawal Al-Rasheed, Nagla F El Oraby, Mahmoud H Mohamed
BACKGROUND: Overdoses of Panadol (APAP) result in hepatic and renal toxicity. Up till now, there is no effective drug for APAP-enhanced nephrotoxicity. This work aims to explore the protective effects of N-acetylcysteine, Thymoquinone (THQ), Curcumin (CUR) and α-Lipoic acid (LA) either alone or in combination against APAP nephrotoxicity, focused on modulation of Bax/Bcl2 pathway. METHODS: APAP was administrated at a single dose then treated with the fore mentioned antioxidants...
May 6, 2017: Pharmacological Reports: PR
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