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Hepatotoxicity

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https://www.readbyqxmd.com/read/28329820/hepatocellular-toxicity-of-imidazole-and-triazole-antimycotic-agents
#1
Patrizia Haegler, Lorenz Joerin, Stephan Krähenbühl, Jamal Bouitbir
Hepatotoxicity has been described for all antimycotic azoles currently marketed. A possible mechanism involving mitochondrial dysfunction has been postulated for ketoconazole, but not for the other azoles. The aim of the current investigations was to study the toxicity of different azoles in human cell models and to find out mechanisms of their toxicity. In HepG2 cells, posaconazole and ketoconazole were cytotoxic starting at 20 and 50 µM and decreased the cellular ATP content starting at 5 and 10 µM, respectively...
January 27, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28328020/detection-of-glutathione-conjugates-of-amiodarone-and-its-reactive-diquinone-metabolites-in-rat-bile-using-mass-spectrometry-tools
#2
Keyur R Parmar, Shalu Jhajra, Saranjit Singh
RATIONALE: Amiodarone is reported to cause hepato and pulmonary toxicity in humans, which has been envisaged to be due to formation of its reactive metabolites, essentially based on its structural similarity to benzbromarone, a drug withdrawn from the market due to reasons of similar hepatotoxicity. Therefore, the purpose of this study was to detect glutathione conjugates of amiodarone and its reactive diquinone metabolites in rat bile using mass spectrometry tools. METHODS: Wistar rats were dosed orally with an amiodarone suspension and bile was collected via bile duct cannulation followed by solid-phase extraction, protein precipitation and centrifugation...
May 30, 2016: Rapid Communications in Mass Spectrometry: RCM
https://www.readbyqxmd.com/read/28327789/prevalence-of-hepatitis-c-virus-and-human-immunodeficiency-virus-in-a-group-of-patients-newly-diagnosed-with-active-tuberculosis-in-porto-alegre-southern-brazil
#3
Cintia Costi, Tarciana Grandi, Maria Laura Halon, Márcia Susana Nunes Silva, Cláudia Maria Dornelles da Silva, Tatiana Schäffer Gregianini, Lia Gonçalves Possuelo, Carla Adriane Jarczewski, Christian Niel, Maria Lucia Rosa Rossetti
BACKGROUND: Porto Alegre is the Brazilian state capital with second highest incidence of tuberculosis (TB) and the highest proportion of people infected with human immunodeficiency virus (HIV) among patients with TB. Hepatitis C virus (HCV) infection increases the risk of anti-TB drug-induced hepatotoxicity, which may result in discontinuation of the therapy. OBJECTIVES: The aim of this study was (i) to estimate prevalence of HCV and HIV in a group of patients newly diagnosed with active TB in a public reference hospital in Porto Alegre and (ii) to compare demographic, behavioural, and clinical characteristics of patients in relation to their HCV infection status...
April 2017: Memórias do Instituto Oswaldo Cruz
https://www.readbyqxmd.com/read/28325735/rescue-preoperative-treatment-with-lugol-s-solution-in-uncontrolled-graves-disease
#4
Jan Calissendorff, Henrik Falhammar
BACKGROUND: Graves' disease is a common cause of hyperthyroidism. Three therapies have been used for decades: pharmacologic therapy, surgery and radioiodine. In case of adverse events, especially agranulocytosis or hepatotoxicity, pre-treatment with Lugol's solution containing iodine/potassium-iodide to induce euthyroidism before surgery could be advocated but has rarely been reported. METHOD: All patients hospitalised due to uncontrolled hyperthyroidism at the Karolinska University Hospital 2005-2015 and treated with Lugol's solution were included...
March 21, 2017: Endocrine Connections
https://www.readbyqxmd.com/read/28323125/minocycline-hepatotoxicity-clinical-characterization-and-identification-of-hla-b%C3%A2-35-02-as-a-risk-factor
#5
Thomas Jacob Urban, Paola Nicoletti, Naga Chalasani, Jose Serrano, Andrew Stolz, Ann Daly, Guruprasad Aithal, John Dillon, Victor Navarro, Joseph Odin, Huiman Barnhart, David Ostrov, Nanye Long, Elizabeth Theresa Cirulli, Paul Brent Watkins, Robert John Fontana
BACKGROUND & AIMS: Minocycline hepatotoxicity can present with prominent autoimmune features in previously healthy individuals. The aim of this study was to identify genetic determinants of minocycline DILI in a well-phenotyped cohort of patients. METHODS: Caucasian patients with minocycline DILI underwent genome-wide genotyping and were compared to unexposed population controls. Human leukocyte antigen (HLA) binding of minocycline was assessed using AutoDock Vina...
March 17, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28323103/cr-vi-induces-cytotoxicity-in-vitro-through-activation-of-ros-mediated-endoplasmic-reticulum-stress-and-mitochondrial-dysfunction-via-the-pi3k-akt-signaling-pathway
#6
Yujing Zhang, Fang Xiao, Xinmin Liu, Kaihua Liu, Xiaoxin Zhou, Caigao Zhong
The occupational and environmental toxicant hexavalent chromium [Cr(VI)] can cause severe damage to the liver; however, the exact mechanisms associated with its toxicity have not been thoroughly demonstrated. In the present study, the underlying mechanisms of Cr(VI)-induced hepatotoxicity were investigated. Our results showed that Cr(VI) inhibited the growth and proliferation of L-02 hepatocytes. Further study revealed that Cr(VI) significantly induced S-phase cell cycle arrest and apoptosis accompanying with the overproduction of reactive oxygen species (ROS)...
March 17, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28322066/hepatoprotective-effect-against-ccl4-induced-acute-liver-damage-in-mice-and-high-performance-liquid-chromatography-mass-spectrometric-method-for-analysis-of-the-constituents-of-extract-of-rubus-crataegifolius
#7
Yongjiao Sun, Lingyun Jia, Zhanbo Huang, Jing Wang, Jincai Lu, Jing Li
This study is an attempt to evaluate the hepatoprotective activity of Rubus Crataegifolius against carbon tetrachloride-induced liver injury in mice. 70% ethanolic, ethyl acetate and n-BuOH extract of R. crataegifolius were administered daily for 14 days in experimental animals before they were treated with CCl4. The hepatoprotective activity of the extracts in this study was compared with the reference drug silymarin. A high-performance liquid chromatography mass spectrometric (HPLC-EIS-MS/MS) method was developed for the determination of the constituents of the extracts...
March 21, 2017: Natural Product Research
https://www.readbyqxmd.com/read/28318525/psoriasis-and-nonalcoholic-fatty-liver-disease
#8
J M Carrascosa, C Bonanad, E Dauden, R Botella, A Olveira-Martín
Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver condition in the West. The prevalence and severity of NAFLD is higher and the prognosis worse in patients with psoriasis. The pathogenic link between psoriasis and NAFLD is chronic inflammation and peripheral insulin resistance, a common finding in diseases associated with psoriasis. NAFLD should therefore be ruled out during the initial evaluation of patients with psoriasis, in particular if they show signs of metabolic syndrome and require systemic treatment...
March 16, 2017: Actas Dermo-sifiliográficas
https://www.readbyqxmd.com/read/28317417/hepatoprotective-effect-of-stachys-pilifera-ethanol-extract-in-carbon-tetrachloride-induce-hepatotoxicity-in-rats
#9
Esmaeel Panahi Kokhdan, Kyomarth Ahmadi, Heibatollah Sadeghi, Hossein Sadeghi, Fahemeh Dadgary, Nazanin Danaei, Mahmoud Reza Aghamaali
CONTEXT: Stachys pilifera Benth (Lamiaceae) has long been used to treat infectious diseases, respiratory and rheumatoid disorders in Iranian folk medicine. Antitumor and antioxidant activity of the plant have been reported. OBJECTIVE: The study was designed to assess the hepatoprotective activity of ethanol extract of Stachys pilifera in carbon tetrachloride (CCl4)-induced hepatotoxicity in rats. MATERIALS AND METHODS: The rats were randomly divided into six equal groups (n = 7)...
December 2017: Pharmaceutical Biology
https://www.readbyqxmd.com/read/28317117/comparative-pharmacokinetic-evaluation-of-lopinavir-and-lopinavir-loaded-solid-lipid-nanoparticles-in-hepatic-impaired-rat-model
#10
Punna Rao Ravi, Rahul Vats
OBJECTIVE: Drug-induced hepatotoxicity is a major cause of concern in patients receiving HIV/TB co-treatment. Lopinavir (LPV), an anti-HIV drug, shows poor plasma exposure due to hepatic first-pass metabolism. In this study, we investigated the effect of hepatotoxicity on pharmacokinetics of free LPV and LPV-loaded solid lipid nanoparticles (LPV SLNs) in male Wistar rats. METHODS: Hepatic impairment model in rats was developed by injecting CCl4 (i.p., 2 ml/kg). Comparative pharmacokinetic (n = 5) and tissue distribution studies (n = 3) were conducted following oral administration (20 mg/kg) of free LPV and LPV SLNs in normal and hepatic impaired rats...
March 19, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/28315688/fullerenol-nanoparticles-prevents-doxorubicin-induced-acute-hepatotoxicity-in-rats
#11
Vesna Jacevic, Aleksandar Djordjevic, Branislava Srdjenovic, Vukosava Milic-Tores, Zoran Segrt, Viktorija Dragojevic-Simic, Kamil Kuca
Doxorubicin (DOX), commonly used antineoplastic agent, affects bone marrow, intestinal tract and heart, but it also has some hepatotoxic effects. Main mechanism of its toxicity is the production of free reactive oxygen species. Polyhidroxilated C60 fullerene derivatives, fullerenol nanoparticles (FNP), act as free radical scavengers in in vitro systems. The aim of the study was to investigate potential FNP protective role against DOX-induced hepatotoxicity in rats. Experiments were performed on adult male Wistar rats...
March 15, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/28315126/screening-for-main-components-associated-with-the-idiosyncratic-hepatotoxicity-of-a-tonic-herb-polygonum-multiflorum
#12
Chunyu Li, Ming Niu, Zhaofang Bai, Congen Zhang, Yanling Zhao, Ruiyu Li, Can Tu, Huifang Li, Jing Jing, Yakun Meng, Zhijie Ma, Wuwen Feng, Jinfa Tang, Yun Zhu, Jinjie Li, Xiaoya Shang, Zhengsheng Zou, Xiaohe Xiao, Jiabo Wang
The main constituents of a typical medicinal herb, Polygonum multiflorum (Heshouwu in Chinese), that induces idiosyncratic liver injury remain unclear. Our previous work has shown that cotreatment with a nontoxic dose of lipopolysaccharide (LPS) and therapeutic dose of Heshouwu can induce liver injury in rats, whereas the solo treatment cannot induce observable injury. In the present work, using the constituent "knock-out" and "knock-in" strategy, we found that the ethyl acetate (EA) extract of Heshouwu displayed comparable idiosyncratic hepatotoxicity to the whole extract in LPS-treated rats...
March 17, 2017: Frontiers of Medicine
https://www.readbyqxmd.com/read/28314361/hepatotoxicity-and-drug-chemical-interaction-toxicity-of-nanoclay-particles-in-mice
#13
Katsuhiro Isoda, Ryutaro Nagata, Tomoya Hasegawa, Yuichiro Taira, Ikuko Taira, Yoshimi Shimizu, Kazuo Isama, Tetsuji Nishimura, Isao Ishida
Nanomaterials are relatively new and unconventional materials with many useful properties, but their effects on biological systems are poorly understood. Nanoclay is a general term for layered mineral silicate nanoparticles that are ideally suited for use in clay-based nanocomposites. The potential biological hazards of nanoclays have not been addressed, however. Therefore, we investigated the in vivo effects and drug interactions of nanoclays. In mice, administration of nanoclay particles via the tail vein led to acute liver injury...
December 2017: Nanoscale Research Letters
https://www.readbyqxmd.com/read/28306135/how-common-are-pulmonary-and-hepatic-adverse-effects-in-older-adults-prescribed-nitrofurantoin
#14
Karin Claussen, Edward Stocks, Deepa Bhat, Jason Fish, Craig D Rubin
OBJECTIVES: To determine the frequency of serious pulmonary and hepatic adverse events (AEs) in persons aged 65 and older prescribed nitrofurantoin. DESIGN: Retrospective electronic health record (EHR) audit of nitrofurantoin prescriptions and associated AEs. SETTING: Urban academic medical center. PARTICIPANTS: All inpatients and outpatients aged 65 and older prescribed nitrofurantoin from January 1, 2010, to December 31, 2014...
March 17, 2017: Journal of the American Geriatrics Society
https://www.readbyqxmd.com/read/28303633/cobalt-chloride-exposure-dose-dependently-induced-hepatotoxicity-through-enhancement-of-cyclooxygenase-2-cox-2-b-cell-associated-protein-x-bax-signaling-and-genotoxicity-in-wistar-rats
#15
Omolola Victoria Awoyemi, Ufuoma Jowafe Okotie, Ademola Adetokunbo Oyagbemi, Temidayo Olutayo Omobowale, Ebunoluwa Racheal Asenuga, Olufunke Eunice Ola-Davies, Blessing Seun Ogunpolu
Cobalt chloride (CoCl2 ) is one of the many environmental contaminants, used in numerous industrial sectors. It is a pollutant with deadly toxicological consequences both in developing and developed countries. We investigated toxicological impact of CoCl2 on hepatic antioxidant status, apoptosis, and genotoxicity. Forty Wistar rats were divided into four groups, 10 rats per group: Group 1 served as control and received clean tap water orally; Group 2 received CoCl2 solution (150 mg/L); Group 3 received CoCl2 solution (300 mg/L); and Group 4 received CoCl2 (600 mg/L) in drinking water for 7 days, respectively...
March 17, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/28298149/methotrexate-induced-mitochondrial-injury-and-cytochrome-c-release-in-rat-liver-hepatocytes
#16
Abdullah Al Maruf, Peter J O'Brien, Parvaneh Naserzadeh, Rozhina Fathian, Ahmad Salimi, Jalal Pourahmad
Methotrexate (MTX) is a folic acid antagonist that is widely used to treat a variety of diseases. One of the most serious side effects of MTX therapy is hepatotoxicity. The potential molecular cytotoxic mechanisms of MTX toward isolated rat hepatocytes were investigated using Accelerated Cytotoxicity Mechanism Screening (ACMS) techniques. A concentration and time dependent increase in cytotoxicity and reactive oxygen species (ROS) formation and a decrease in mitochondrial membrane potential (MMP) were observed with MTX...
March 16, 2017: Drug and Chemical Toxicology
https://www.readbyqxmd.com/read/28296721/single-pemetrexed-is-noninferior-to-platinum-based-pemetrexed-doublet-as-first-line-treatment-on-elderly-chinese-patients-with-advanced-nonsquamous-nonsmall-cell-lung-cancer
#17
Xiaolin Pu, Wei Li, Binbin Lu, Zhaoxia Wang, Min Yang, Weifei Fan, Lijuan Meng, Zhigang Lv, Yuchun Xie, Jun Wang
BACKGROUND: To evaluate the clinical efficacy and toxicity of single pemetrexed treatment compared with platinum-based pemetrexed doublet pemetrexed-based as first-line treatment for advanced nonsquamous nonsmall cell lung cancer (NS-NSCLC) in elderly Chinese patients. METHODS: The study retrospectively reviewed 175 elderly Chinese patients with NS-NSCLC from June 2010 to September 2013: 90 patients received single pemetrexed treatment, 45 received pemetrexed plus oxaliplatin, and 40 received pemetrexed plus carboplatin...
March 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28295935/real-time-in%C3%A2-vivo-hepatotoxicity-monitoring-through-chromophore-conjugated-photon-upconverting-nanoprobes
#18
Juanjuan Peng, Animesh Samanta, Xiao Zeng, Sanyang Han, Lu Wang, Dongdong Su, Daniel Teh Boon Loong, Nam-Young Kang, Sung-Jin Park, Angelo Homayoun All, Wenxuan Jiang, Lin Yuan, Xiaogang Liu, Young-Tae Chang
Drug toxicity is a long-standing concern of modern medicine. A typical anti-pain/fever drug paracetamol often causes hepatotoxicity due to peroxynitrite ONOO(-) . Conventional blood tests fail to offer real-time unambiguous visualization of such hepatotoxicity in vivo. Here we report a luminescent approach to evaluate acute hepatotoxicity in vivo by chromophore-conjugated upconversion nanoparticles. Upon injection, these nanoprobes mainly accumulate in the liver and the luminescence of nanoparticles remains suppressed owing to energy transfer to the chromophore...
March 15, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28295449/hepatic-mtdna-tlr9-microrna-223-forms-a-negative-feedback-loop-to-limit-neutrophil-over-activation-and-acetaminophen-hepatotoxicity
#19
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/28294041/tacrine-based-multifunctional-agents-in-alzheimer-s-disease-an-old-story-in-continuous-development
#20
Andrea Milelli, Angela De Simone, Nicole Ticchi, Huan Huan Chen, Nibal Betari, Vincenza Andrisano, Vincenzo Tumiatti
Tacrine is no longer used for the treatment of Alzheimer's disease (AD) as oral acetylcholinesterase (AChE) inhibitor (AChEI) mainly due to its hepatotoxic effects. Notwithstanding, it is still one of the most famous drugs. Indeed, since the discovery of the "non-cholinergic" AChE's activities and the seminal paper from Pang and coworkers reporting the discovery of a tacrine-dimer, bis(7)-tacrine, tacrine has been used from legions of medicinal chemists as a starting point to develop new multi target ligands (MTLs), able to interfere with biochemical pathways and targets whose dysregulation seems to be involved in the development of AD...
March 9, 2017: Current Medicinal Chemistry
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