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https://www.readbyqxmd.com/read/28545014/paracetamol-causes-endocrine-disruption-and-hepatotoxicity-in-male-fish-rhamdia-quelen-after-subchronic-exposure
#1
Izonete Cristina Guiloski, João Luiz Coelho Ribas, Laercio Dante Stein Piancini, Ana Carolina Dagostim, Silvana Maris Cirio, Luis Fernando Fávaro, Suelen Lúcio Boschen, Marta Margarete Cestari, Cláudio da Cunha, Helena Cristina Silva de Assis
Paracetamol is one of the most widely sold non-prescription drugs. This study aimed to evaluate the effects of the paracetamol on reproductive, biochemical, genetic, histopathological and hematogical biomarkers by waterborne exposure. Male fish of Rhamdia quelen were exposed to environmental concentrations of paracetamol (0, 0.25, 2.5μg/L) in a semi-static bioassay for 21days. Hemoglobin and hematocrit were reduced upon exposure to 0.25μg/L of paracetamol. Leukocytes and thrombocytes increased after paracetamol exposure...
May 8, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/28543822/good-for-the-lung-but-bad-for-the-liver-garlic-induced-hepatotoxicity-following-liver-transplantation
#2
S A Shaikh, S Tischer, E K Choi, R J Fontana
WHAT IS KNOWN AND OBJECTIVE: Limited data exist surrounding the metabolism and safety of garlic supplements. CASE DESCRIPTION: A patient with a history of hepatopulmonary syndrome (HPS) and orthotopic liver transplantation was admitted to our surgery transplant service with severe hypoxaemia. The patient was started on high-dose Garlicin Cardio(®) (Allium sativum) for HPS and soon after had elevated liver function tests. Garlicin Cardio(®) was discontinued and liver enzymes normalized...
May 25, 2017: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/28539743/hepatoprotective-antihyperlipidemic-and-anti-inflammatory-activity-of-moringa-oleifera-in-diabetic-induced-damage-in-male-wistar-rats
#3
Elizabeth I Omodanisi, Yapo G Aboua, Novel N Chegou, Oluwafemi O Oguntibeju
BACKGROUND: The number of individuals with diabetes is increasing daily, and diabetes is presently estimated to affect about 422 million adults worldwide. Conventional drugs used to treat diabetes are not without severe side effects, accessibility, and affordability. This study elucidates the potential effects of Moringa oleifera (MO) leaves extract to manage and treat diabetes induced in male Wistar rats. MATERIALS AND METHODS: Adult male Wistar rats were randomly divided into four groups (n = 12/group): NC - nondiabetic rats (positive control), MO - nondiabetic-treated rats, DM - diabetic rats (negative control), DM + MO - diabetic-treated rats...
April 2017: Pharmacognosy Research
https://www.readbyqxmd.com/read/28536862/mechanisms-of-hepatotoxicity-associated-with-the-monocyclic-%C3%AE-lactam-antibiotic-bal30072
#4
Franziska Paech, Simon Messner, Jochen Spickermann, Mathias Wind, Anne-Hortense Schmitt-Hoffmann, Anne Therese Witschi, Brett A Howell, Rachel J Church, Jeff Woodhead, Marc Engelhardt, Stephan Krähenbühl, Martina Maurer
BAL30072 is a new monocyclic β-lactam antibiotic under development which provides a therapeutic option for the treatment of severe infections caused by multi-drug-resistant Gram-negative bacteria. Despite the absence of liver toxicity in preclinical studies in rats and marmosets and in single dose clinical studies in humans, increased transaminase activities were observed in healthy subjects in multiple-dose clinical studies. We, therefore, initiated a comprehensive program to find out the mechanisms leading to hepatocellular injury using HepG2 cells (human hepatocellular carcinoma cell line), HepaRG cells (inducible hepatocytes derived from a human hepatic progenitor cell line), and human liver microtissue preparations...
May 23, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28535741/effects-of-n-acetyl-cysteine-on-oxidative-stress-and-tnf-%C3%AE-gene-expression-in-diclofenac-induced-hepatotoxicity-in-rats
#5
Ali Nouri, Esfandiar Heidarian, Morteza Nikoukar
The consumption of nonsteroidal anti-inflammatory drug, such as diclofenac, can lead to hepatotoxicity. In the present study, protective effect of N-acetyl cysteine (NAC) on diclofenac-induced hepatotoxicity was investigated. Thirty two male rats were divided into four groups. Group 1 (control group) was treated with normal saline (1 ml/kg, i.p.) for 4 days. Group 2 (test without treatment) received diclofenac only (50 mg/kg, i.p.) for 4 days. Groups 3 and 4 received diclofenac (50 mg/kg, i.p.) plus NAC (150mg/kg, p...
May 24, 2017: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/28535545/portuguese-recommendations-for-the-use-of-methotrexate-in-rheumatic-diseases-2016-update
#6
Ana Catarina Duarte, Daniela Santos-Faria, Maria João Gonçalves, Alexandre Sepriano, Ana Filipa Mourão, Cátia Duarte, Joana Sousa Neves, Ana Filipa Águeda, Pedro Ávila Ribeiro, Alexandra Daniel, Adriano Neto, Ana Cordeiro, Ana Rodrigues, Anabela Barcelos, Cândida Silva, Cristina Ponte, Elsa Vieira-Sousa, Filipa Teixeira, Filipa Oliveira-Ramos, Filipe Araújo, Filipe Barcelos, Helena Canhão, Helena Santos, João Ramos, Joaquim Pereira, José Costa, José António Melo Gomes, Luís Cunha-Miranda, Lúcia Costa, Marcos Cerqueira, Margarida Cruz, Maria José Santos, Miguel Bernardes, Paula Oliveira, Pedro Abreu, Ricardo Figueira, Rita Barros, Sandra Falcão, Patrícia Pinto, Sofia Pimenta, Susana Capela, Vitor Teixeira, João Eurico Fonseca
BACKGROUND: Methotrexate (MTX) is the first-line drug in the treatment of rheumatoid arthritis (RA) and the most commonly prescribed disease modifying anti-rheumatic drug. Moreover, it is also used as an adjuvant drug in patients under biologic therapies, enhancing the efficacy of biologic agents. OBJECTIVES: To review the literature and update the Portuguese recommendations for the use of MTX in rheumatic diseases first published in 2009. METHODS: The first Portuguese guidelines for the use of MTX in rheumatic diseases were published in 2009 and were integrated in the multinational 3E Initiative (Evidence Expertise Exchange) project...
May 9, 2017: Acta Reumatológica Portuguesa
https://www.readbyqxmd.com/read/28533121/recent-progress-in-hepatocyte-culture-models-and-their-application-to-the-assessment-of-drug-metabolism-transport-and-toxicity-in-drug-discovery-the-value-of-tissue-engineering-for-the-successful-development-of-a-microphysiological-system
#7
REVIEW
Kazuhiro Tetsuka, Masato Ohbuchi, Kenji Tabata
Tissue engineering technology has provided many useful culture models. This article reviews the merits of this technology in a hepatocyte culture system, and describes the applications of the sandwich-cultured hepatocyte model in drug discovery. In addition, we also review recent investigations of the utility of the three-dimensional bioprinted human liver tissue model and spheroid model. Finally, we present the future direction and developmental challenges of a hepatocyte culture model for the successful establishment of a microphysiological system, represented as an organ-on-a-chip and even as a human-on-a-chip...
May 19, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28527127/evaluation-of-heparg-cells-for-the-assessment-of-indirect-drug-induced-hepatotoxicity-using-inh-as-a-model-substance
#8
Anika Mann, Thomas Pelz, Knut Rennert, Alexander Mosig, Michael Decker, Amelie Lupp
HepaRG cells are widely used as an in vitro model to assess drug-induced hepatotoxicity. However, only few studies exist so far regarding their suitability to detect the effects of drugs requiring a preceding activation via the cytochrome P450 (CYP) system. A prototypic substance is the anti-tuberculosis agent INH, which is metabolized into N-acetylhydrazine, which then triggers hepatotoxicity. Therefore, the aim of the present study was to test if this effect can also be detected in HepaRG cells and if it can be counteracted by the known hepatoprotectant silibinin...
May 19, 2017: Human Cell
https://www.readbyqxmd.com/read/28521054/in-silico-prediction-of-drug-induced-liver-injury-based-on-adverse-drug-reaction-reports
#9
Xiang-Wei Zhu, Shao-Jing Li
Drug-induced liver injury (DILI) is a major cause of drug attrition. Currently existing Quantitative Structure-Activity Relationship (QSAR) models have limited predictive capabilities for DILI. Furthermore, their practical applications were limited by lack of new hepatotoxicity data. In this study, we first collected and curated a novel set of 122 DILI-positive and 932 DILI-negative drugs from online adverse drug reports using proportional reporting ratios as the signal detection method. Second, three strategies (under-sampling the majority class, synthetic minority over-sampling technique, and adjusting decision threshold approach) were employed to develop predictive classification models to cope with the unbalanced dataset...
May 17, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28509890/balancing-low-density-lipoprotein-cholesterol-reduction-and-hepatotoxicity-with-lomitapide-mesylate-and-mipomersen-in-patients-with-homozygous-familial-hypercholesterolemia
#10
Jane I Won, Jun Zhang, Kristen M Tecson, Peter A McCullough
Homozygous familial hypercholesterolemia (HoFH) is an autosomal codominant disorder manifested by high concentrations of total cholesterol and low-density lipoprotein (LDL) cholesterol, and premature cardiovascular disease. Despite conventional lipid-lowering therapy, LDL cholesterol levels remain elevated in patients with HoFH; these patients are considered to be at high risk for cardiovascular events. In 2012-2013, two drugs with novel mechanisms of action were approved by the US Food and Drug Administration for the treatment of HoFH: lomitapide mesylate and mipomersen...
2017: Reviews in Cardiovascular Medicine
https://www.readbyqxmd.com/read/28507111/real-life-assessment-of-the-safety-and-effectiveness-of-the-new-tablet-and-intravenous-formulations-of-posaconazole-in-the-prophylaxis-of-invasive-fungal-infections-analysis-of-343-courses
#11
Frank P Tverdek, Sang Taek Heo, Samuel L Aitken, Bruno Granwehr, Dimitrios P Kontoyiannis
BACKGROUND: Posaconazole is the preferred mold-active azole for prophylaxis against invasive fungal infection (IFI) in patients with hematologic malignancy (HM). Delayed release tablet and intravenous formulations of posaconazole have recently become available, but clinical data are limited. We sought to examine the real-world pharmacokinetics and prophylactic effectiveness of the new formulations of posaconazole given as prophylaxis in patients with HM. METHODS: A retrospective cohort of all consecutive adult inpatients with HM who received ≥3 days of posaconazole as tablet or intravenous from 12/1/2013-12/31/2015 for primary IFI prophylaxis at MD Anderson Cancer center...
May 15, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28505368/farnesoid-x-receptor-protects-against-low-dose-carbon-tetrachloride-induced-liver-injury-through-the-taurocholate-jnk-pathway
#12
Shogo Takahashi, Naoki Tanaka, Srujana Golla, Tatsuki Fukami, Kristopher W Krausz, Marianne A Polunas, Blair C Weig, Yusuke Masuo, Cen Xie, Changtao Jiang, Frank J Gonzalez
Hepatotoxicity is of major concern for humans exposed to industrial chemicals and drugs. Disruption of farnesoid X receptor (FXR), a master regulator of bile acid (BA) metabolism, enhanced the sensitivity to liver injury in mice after toxicant exposure, but the precise mechanism remains unclear. In this study, the interconnection between BA metabolism, FXR, and chemically-induced hepatotoxicity was investigated using metabolomics, Fxr-null mice and hepatocytes, and adenovirus. A single low-dose intraperitoneal injection of carbon tetrachloride (CCl4), an inducer of acute hepatitis in mice, resulted in more severe hepatocyte damage and higher induction of pro-inflammatory mediators, such as chemokine (C-C motif) ligand 2 (Ccl2), in Fxr-null mice...
May 15, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28501036/tuberculosis-in-liver-transplant-recipients-a-report-of-eight-cases-during-a-five-year-period
#13
Diana Póvoas, João Machado, Rui Perdigoto, Ana Morbey, Júlio Veloso, Helena Glória, Élia Mateus, Américo Martins, Fernando Maltez, Eduardo Barroso
INTRODUCTION: Tuberculosis incidence in Portugal ranged from 20 to 22 cases per 100 000 inhabitants between 2010 and 2014. Tuberculosis incidence in liver transplant recipients is not precisely known, but it is estimated to be higher than among the general population. Tuberculosis in liver transplant recipients is particularly challenging because of the atypical clinical presentation and side effects of the antibacillary drugs and their potential interactions with immunosuppressive therapies...
January 31, 2017: Acta Médica Portuguesa
https://www.readbyqxmd.com/read/28499383/nintedanib-antiangiogenic-inhibitor-effectiveness-in-delaying-adenocarcinoma-progression-in-transgenic-adenocarcinoma-of-the-mouse-prostate-tramp
#14
Raquel Frenedoso da Silva, Ellen Nogueira-Pangrazi, Larissa Akemi Kido, Fabio Montico, Sarah Arana, Dileep Kumar, Komal Raina, Rajesh Agarwal, Valéria Helena Alves Cagnon
BACKGROUND: In recent times, anti-cancer treatments have focused on Fibroblast Growth Factor (FGF) and Vascular-Endothelial Growth Factor (VEGF) pathway inhibitors so as to target tumor angiogenesis and cellular proliferation. One such drug is Nintedanib; the present study evaluated the effectiveness of Nintedanib treatment against in vitro proliferation of human prostate cancer (PCa) cell lines, and growth and progression of different grades of PCa lesions in pre-clinical PCa transgenic adenocarcinoma for the mouse prostate (TRAMP) model...
May 12, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28496041/a-rapid-mitochondrial-toxicity-assay-utilizing-rapidly-changing-cell-energy-metabolism
#15
Yosuke Sanuki, Tetsuro Araki, Osamu Nakazono, Kazuyuki Tsurui
Drug-induced liver injury is a major cause of safety-related drug-marketing withdrawals. Several drugs have been reported to disrupt mitochondrial function, resulting in hepatotoxicity. The development of a simple and effective in vitro assay to identify the potential for mitochondrial toxicity is thus desired to minimize the risk of causing hepatotoxicity and subsequent drug withdrawal. An in vitro test method called the "glucose-galactose" assay is often used in drug development but requires prior-culture of cells over several passages for mitochondrial adaptation, thereby restricting use of the assay...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28489727/pharmacology-of-thiopurine-therapy-in-inflammatory-bowel-disease-and-complete-blood-cell-count-outcomes-a-five-year-database-study
#16
Berrie Meijer, Abraham J Wilhelm, Chris Jj Mulder, Gerd Bouma, Adriaan A van Bodegraven, Nanne Kh de Boer
BACKGROUND: Thiopurines Are The Prerequisite For Immunomodulation In Inflammatory Bowel disease (IBD) therapy. When administered in high (oncological) dose, thiopurine metabolites act as purine antagonists, causing DNA-strand breakage and myelotoxicity. In lower IBD dosages, the mode of action is primarily restricted to anti-inflammatory effects. Then, myelosuppression and hepatotoxicity are the most common adverse events of thiopurines. The aim of this study was to assess the effect of thiopurine metabolites on hematologic and hepatic parameters and to determine which patient characteristics are related to generation of thiopurine metabolites...
May 6, 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28486596/troglitazone-inhibits-bile-acid-amidation-a-possible-risk-factor-for-liver-injury
#17
Eiichiro Ogimura, Tetsuya Nakagawa, Jiro Deguchi, Shuichi Sekine, Kousei Ito, Kiyoko Bando
Troglitazone and pioglitazone were developed as thiazolidinedione-type anti-diabetes drugs, but only troglitazone was withdrawn from the markets due to severe liver injury. As both troglitazone and its sulfate metabolite are strong inhibitors of the bile salt export pump (BSEP), troglitazone-induced bile acid (BA) retention is thought to be one of the underlying mechanisms of liver injury. However, pioglitazone is also a strong BSEP inhibitor, indicating other mechanisms may also be involved in troglitazone-induced BA retention...
May 9, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28486401/drug-induced-liver-injury-cascade-of-events-leading-to-cell-death-apoptosis-or-necrosis
#18
REVIEW
Andrea Iorga, Lily Dara, Neil Kaplowitz
Drug-induced liver injury (DILI) can broadly be divided into predictable and dose dependent such as acetaminophen (APAP) and unpredictable or idiosyncratic DILI (IDILI). Liver injury from drug hepatotoxicity (whether idiosyncratic or predictable) results in hepatocyte cell death and inflammation. The cascade of events leading to DILI and the cell death subroutine (apoptosis or necrosis) of the cell depend largely on the culprit drug. Direct toxins to hepatocytes likely induce oxidative organelle stress (such as endoplasmic reticulum (ER) and mitochondrial stress) leading to necrosis or apoptosis, while cell death in idiosyncratic DILI (IDILI) is usually the result of engagement of the innate and adaptive immune system (likely apoptotic), involving death receptors (DR)...
May 9, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28479956/a-single-zidovudine-azt-administration-delays-hepatic-cell-proliferation-by-altering-oxidative-state-in-the-regenerating-rat-liver
#19
Armando Butanda-Ochoa, Diego Rolando Hernández-Espinosa, Marisela Olguín-Martínez, Lourdes Sánchez-Sevilla, Mario R Rodríguez, Benito Chávez-Rentería, Alberto Aranda-Fraustro, Rolando Hernández-Muñoz
The 3'-azido-3'-deoxythymidine or Zidovudine (AZT) was the first antiretroviral drug used in the treatment of HIV patients, which has good effectiveness but also hepatotoxic side effects that include cell cycle arrest and oxidative/nitrative mitochondrial damage. Whether such an oxidative damage may affect the proliferative-regenerative capacity of liver remains to be clearly specified at doses commonly used in the clinical practice. In this study, we described the oxidative-proliferative effect of AZT administered at a common clinical dose in rat liver submitted to 70% partial hepatectomy (PH)...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28479099/protective-effect-of-chlorogenic-acid-against-methotrexate-induced-oxidative-stress-inflammation-and-apoptosis-in-rat-liver-an-experimental-approach
#20
Nemat Ali, Summya Rashid, Sana Nafees, Syed Kazim Hasan, Ayaz Shahid, Ferial Majed, Sarwat Sultana
Methotrexate (MTX) is a drug which is used to treat different types of cancers but hepatotoxicity limits its clinical use. Chlorogenic acid (CGA) is one of the most abundant naturally occurring polyphenols in the human diet. Here, we assessed the effect of CGA against MTX-induced hepatotoxicity and investigated the underlying possible mechanisms in Wistar Rats. Rats were pre-treated with CGA (50 or 100 mg kg/b.w) and administered a single dose of MTX (20 mg/kg, b.w.). MTX caused hepatotoxicity as evidenced by significant increase in serum toxicity markers, histopathological changes...
May 4, 2017: Chemico-biological Interactions
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