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Drug-induced 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/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
#2
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
#3
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
#4
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/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
#5
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/28317117/comparative-pharmacokinetic-evaluation-of-lopinavir-and-lopinavir-loaded-solid-lipid-nanoparticles-in-hepatic-impaired-rat-model
#6
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/28315126/screening-for-main-components-associated-with-the-idiosyncratic-hepatotoxicity-of-a-tonic-herb-polygonum-multiflorum
#7
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/28293388/protective-role-of-licochalcone-b-against-ethanol-induced-hepatotoxicity-through-regulation-of-erk-signaling
#8
Xiao-Peng Gao, Dong-Wei Qian, Zhen Xie, Hao Hui
OBJECTIVES: Oxidative stress has been established as a key cause of alcohol-induced hepatotoxicity. Licochalcone B, an extract of licorice root, has shown antioxidative properties. This study was to investigate the effects and mechanisms of licochalcone B in ethanol-induced hepatic injury in an in vitro study. MATERIALS AND METHODS: An in vitro model of Ethanol-induced cytotoxicity in BRL cells was used in this study. Cell injury was assessed using WST-1 assay and lactate dehydrogenase, alanine transaminase, and aspartate aminotransferase release assay...
February 2017: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/28273564/hepatotoxicity-and-proteomic-mechanism-of-di-n-butyl-di-4-chlorobenzohydroxamato-tin-iv-dbdct-in-vivo
#9
Li Tang, Jie-Ran Luo, Yun-Lan Li, Rui Ge, Qing-Shan Li
Di-n-butyl-di-(4-chlorobenzohydroxamato)tin(IV) (DBDCT) is an anti-tumour organotin(IV) compound with hepatotoxicity. To investigate the hepatotoxicity and mechanisms of DBDCT in vivo, proteomic technology 2D gel combined with MALDI-TOF-MS was used in our research. Results indicated that DBDCT increased AST, AKP and ACP activities and decreased ALT activity. Further, sporadic eosinophilic changes and nuclear pyknosis were visible in hepatic pathological observation. Proteomic analysis showed that twenty-two proteins involved in amino acid, nucleic acid, carbohydrate and lipid metabolism, stress response, multicellular organism development and cell apoptosis were differentially expressed and identified...
February 24, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/28263783/establishment-of-a-novel-mouse-model-for-pioglitazone-induced-skeletal-muscle-injury
#10
Sho Akai, Shingo Oda, Tsuyoshi Yokoi
Skeletal muscle (SKM) injury is one of the major safety concerns in risk assessment for drug development. However, no appropriate pre-clinical animal model exists to evaluate drug-induced SKM injury except that caused by fibrates and statins. Thiazolidinedione, a PPARγ agonistic drug for type 2 diabetes mellitus, is widely used clinically but can induce adverse effects such as hepatotoxicity and SKM injury, as has been reported in recent decades. Moreover, thiazolidinedione-induced SKM injury has only been reported in humans, and no evidence of SKM injury has been observed in rodents...
March 2, 2017: Toxicology
https://www.readbyqxmd.com/read/28263289/establishment-of-a-mouse-model-of-enalapril-induced-liver-injury-and-investigation-of-the-pathogenesis
#11
Yuji Shirai, Shingo Oda, Sayaka Makino, Koichi Tsuneyama, Tsuyoshi Yokoi
Drug-induced liver injury (DILI) is a major concern in drug development and clinical drug therapy. Since the underlying mechanisms of DILI have not been fully understood in most cases, elucidation of the hepatotoxic mechanisms of drugs is expected. Although enalapril (ELP), an angiotensin-converting enzyme inhibitor, has been reported to cause liver injuries with a low incidence in humans, the precise mechanisms by which ELP causes liver injury remains unknown. In this study, we established a mouse model of ELP-induced liver injury and analyzed the mechanisms of its hepatotoxicity...
March 6, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28262508/the-role-of-ntcp-oatp2-bsep-and-mrp2-in-liver-injury-induced-by-dioscorea-bulbifera-l-and-diosbulbin-b-in-mice
#12
Xiao-Yu Qu, Li-Na Tao, Si-Xi Zhang, Jing-Meng Sun, Jun-Qi Niu, Yan-Hua Ding, Yan-Qing Song
Dioscorea bulbifera L. (DB) is a traditional Chinese herb used in thyroid disease and cancer. However, the clinical use of DB remains a challenge due to its hepatotoxicity, which is caused, in part, by the presence of Diosbulbin B (DIOB), a toxin commonly found in DB extracts. As abnormal expression of hepatobiliary transporters plays an important role in drug-induced liver injury, we assessed the hepatotoxicity induced by DB and DIOB, and explored their impacts on hepatobiliary transporter expression levels...
February 28, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/28261269/comparative-hepatotoxicity-of-fluconazole-ketoconazole-itraconazole-terbinafine-and-griseofulvin-in-rats
#13
Star Khoza, Ishmael Moyo, Denver Ncube
Oral ketoconazole was recently the subject of regulatory safety warnings because of its association with increased risk of inducing hepatic injury. However, the relative hepatotoxicity of antifungal agents has not been clearly established. The aim of this study was to compare the hepatotoxicity induced by five commonly prescribed oral antifungal agents. Rats were treated with therapeutic oral doses of griseofulvin, fluconazole, itraconazole, ketoconazole, and terbinafine. After 14 days, only ketoconazole had significantly higher ALT levels (p = 0...
2017: Journal of Toxicology
https://www.readbyqxmd.com/read/28259712/molecular-docking-synthesis-and-biological-screening-of-mefenamic-acid-derivatives-as-anti-inflammatory-agents
#14
Jignasa K Savjani, Suja Mulamkattil, Bhavesh Variya, Snehal Patel
Drug induced gastrointestinal ulceration, renal side effects and hepatotoxicity are the main causes of numerous Non-Steroidal Anti-inflammatory Drugs (NSAIDs). Cyclooxygenase-2 (COX-2) inhibitors discovered to decrease the gastrointestinal issues, but unfortunately, most of them are associated with major cardiovascular adverse effects. Along these lines, various new strategies and frameworks were developed wherein basic alterations of the present medications were accounted for. The aim of the study was to prepare derivatives of mefenamic acid to evaluate anti-inflammatory activity with fewer adverse reactions...
March 1, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28257659/comprehensive-assessment-of-cucurbitacin-e-related-hepatotoxicity-and-drug-drug-interactions-involving-cyp3a-and-p-glycoprotein
#15
Jian Lu, Yuanjin Zhang, Min Sun, Mingyao Liu, Xin Wang
BACKGROUND: Cucurbitacin E (CuE), a tetracyclic triterpenoid isolated from Cucurbitaceae, possesses many pharmacological activities especially anti-cancer. PURPOSE: The aim of this investigation was to comprehensively assess CuE related hepatotoxicity and potential drug-drug interactions involving CYP3A and P-glycoprotein (P-gp). STUDY DESIGN AND METHODS: Four common cytotoxicity assays (MTS, SRB, NRU and apoptosis assays) were used to evaluate the hepatotoxicity of CuE in human hepatocellular carcinoma HepG2 cells...
March 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28253087/genome-wide-association-studies-for-idiosyncratic-drug-induced-hepatotoxicity-looking-back-looking-forward-to-next-generation-innovation
#16
Zelalem Petros, Eyasu Makonnen, Eleni Aklillu
Idiosyncratic drug-induced hepatotoxicity is a formidable challenge for rational drug discovery and development, as well as the science of personalized medicine. There is evidence that hereditary factors, in part, contribute to drug toxicity. This expert analysis and review offer the insights gained, and the challenges ahead, for genome-wide association studies (GWASs) of idiosyncratic drug-induced hepatotoxicity. Published articles on genome-wide and subsequent replication studies were systematically searched in the PubMed electronic database...
March 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/28250317/strategic-drug-design-to-avoid-the-metabolic-activation-of-hepatotoxic-drugs
#17
Tomoyuki Ohe, Kyoko Takahashi, Shigeo Nakamura, Tadahiko Mashino
 Adverse reactions are one of the most important issues in drug development, as well as in the therapeutic usage of drugs during the post-approval stage. Specifically, idiosyncratic adverse drug reactions (IDR) occur in only a small group of patients who are treated with certain drugs, and are unpredictable. It is widely accepted that drug-induced IDR is often associated with CYP-mediated bioactivation. Benzbromarone (BBR) is effective in the treatment of hyperuricemia, and has been used as an effective drug in Japan for a long time...
2017: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
https://www.readbyqxmd.com/read/28248534/sirtuin-activating-compounds-stacs-alleviate-d-galactosamine-lipopolysaccharide-induced-hepatotoxicity-in-rats-involvement-of-sirtuin-1-and-heme-oxygenase-1
#18
M K Kemelo, N Kutinová Canová, A Horinek, H Farghali
Sirtuin activating compounds (STACs) attenuate various type of liver insults through mechanisms which are not fully understood. In the present study, we investigated the ameliorative potential of quercetin (natural polyphenol) and SRT1720 (synthetic SIRT1 activator) against D-galactosamine/lipopolysaccharide-induced hepatotoxicity (an experimental model of acute liver failure). Moreover, we compared and contrasted the roles of stress responsive enzymes, sirtuin 1 (SIRT1) and heme oxygenase 1 (HO-1) in hepatoprotection/ hepatotoxicity...
February 28, 2017: Physiological Research
https://www.readbyqxmd.com/read/28239160/insights-into-the-molecular-mechanisms-of-polygonum-multiflorum-thunb-induced-liver-injury-a-computational-systems-toxicology-approach
#19
Yin-Yin Wang, Jie Li, Zeng-Rui Wu, Bo Zhang, Hong-Bin Yang, Qin Wang, Ying-Chun Cai, Gui-Xia Liu, Wei-Hua Li, Yun Tang
An increasing number of cases of herb-induced liver injury (HILI) have been reported, presenting new clinical challenges. In this study, taking Polygonum multiflorum Thunb (PmT) as an example, we proposed a computational systems toxicology approach to explore the molecular mechanisms of HILI. First, the chemical components of PmT were extracted from 3 main TCM databases as well as the literature related to natural products. Then, the known targets were collected through data integration, and the potential compound-target interactions (CTIs) were predicted using our substructure-drug-target network-based inference (SDTNBI) method...
February 27, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28225807/increased-liver-specific-proteins-in-circulating-extracellular-vesicles-as-potential-biomarkers-for-drug-and-alcohol-induced-liver-injury
#20
Young-Eun Cho, Eun-Ju Im, Pyong-Gon Moon, Esteban Mezey, Byoung-Joon Song, Moon-Chang Baek
Drug- and alcohol-induced liver injury are a leading cause of liver failure and transplantation. Emerging evidence suggests that extracellular vesicles (EVs) are a source of biomarkers because they contain unique proteins reflecting the identity and tissue-specific origin of the EV proteins. This study aimed to determine whether potentially hepatotoxic agents, such as acetaminophen (APAP) and binge alcohol, can increase the amounts of circulating EVs and evaluate liver-specific EV proteins as potential biomarkers for liver injury...
2017: PloS One
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