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drug induced liver toxicity

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https://www.readbyqxmd.com/read/28219592/urgent-liver-transplantation-for-dietary-supplements-an-under-recognized-problem
#1
L L Wong, L Lacar, M Roytman, S L Orloff
BACKGROUND: The recent outbreak of acute liver failure caused by herbal/dietary supplements (HDS) in Hawaii prompted evaluation of those patients who underwent emergency liver transplantation (LT) for HDS in the United States. METHODS: We queried the Scientific Registry of Transplant Recipients (2003-2015) to identify patients who underwent urgent LT for acute hepatic necrosis (AHN) and identified those with HDS use. This group of patients was then characterized...
March 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28217372/psychotropic-drugs-and-liver-disease-a-critical-review-of-pharmacokinetics-and-liver-toxicity
#2
REVIEW
Diogo Telles-Correia, António Barbosa, Helena Cortez-Pinto, Carlos Campos, Nuno B F Rocha, Sérgio Machado
The liver is the organ by which the majority of substances are metabolized, including psychotropic drugs. There are several pharmacokinetic changes in end-stage liver disease that can interfere with the metabolization of psychotropic drugs. This fact is particularly true in drugs with extensive first-pass metabolism, highly protein bound drugs and drugs depending on phase I hepatic metabolic reactions. Psychopharmacological agents are also associated with a risk of hepatotoxicity. The evidence is insufficient for definite conclusions regarding the prevalence and severity of psychiatric drug-induced liver injury...
February 6, 2017: World Journal of Gastrointestinal Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28217095/endogenous-protein-interactome-of-human-udp-glucuronosyltransferases-exposed-by-untargeted-proteomics
#3
Michèle Rouleau, Yannick Audet-Delage, Sylvie Desjardins, Mélanie Rouleau, Camille Girard-Bock, Chantal Guillemette
The conjugative metabolism mediated by UDP-glucuronosyltransferase enzymes (UGTs) significantly influences the bioavailability and biological responses of endogenous molecule substrates and xenobiotics including drugs. UGTs participate in the regulation of cellular homeostasis by limiting stress induced by toxic molecules, and by controlling hormonal signaling networks. Glucuronidation is highly regulated at genomic, transcriptional, post-transcriptional and post-translational levels. However, the UGT protein interaction network, which is likely to influence glucuronidation, has received little attention...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28216958/-1-h-nmr-based-serum-metabolomics-reveals-erythromycin-induced-liver-toxicity-in-albino-wistar-rats
#4
Atul Rawat, Durgesh Dubey, Anupam Guleria, Umesh Kumar, Amit K Keshari, Swati Chaturvedi, Anand Prakash, Sudipta Saha, Dinesh Kumar
INTRODUCTION: Erythromycin (ERY) is known to induce hepatic toxicity which mimics other liver diseases. Thus, ERY is often used to produce experimental models of drug-induced liver-toxicity. The serum metabolic profiles can be used to evaluate the liver-toxicity and to further improve the understanding of underlying mechanism. OBJECTIVE: To establish the serum metabolic patterns of Erythromycin induced hepatotoxicity in albino wistar rats using (1)H NMR based serum metabolomics...
October 2016: Journal of Pharmacy & Bioallied Sciences
https://www.readbyqxmd.com/read/28216624/dual-targeted-hybrid-nanoparticles-of-synergistic-drugs-for-treating-lung-metastases-of-triple-negative-breast-cancer-in-mice
#5
Tian Zhang, Preethy Prasad, Ping Cai, Chunsheng He, Dan Shan, Andrew Michael Rauth, Xiao Yu Wu
Lung metastasis is the major cause of death in patients with triple negative breast cancer (TNBC), an aggressive subtype of breast cancer with no effective therapy at present. It has been proposed that dual-targeted therapy, ie, targeting chemotherapeutic agents to both tumor vasculature and cancer cells, may offer some advantages. The present work was aimed to develop a dual-targeted synergistic drug combination nanomedicine for the treatment of lung metastases of TNBC. Thus, Arg-Gly-Asp peptide (RGD)-conjugated, doxorubicin (DOX) and mitomycin C (MMC) co-loaded polymer-lipid hybrid nanoparticles (RGD-DMPLN) were prepared and characterized...
February 20, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28209108/acute-temozolomide-induced-liver-injury%C3%A2-mixed-type-hepatocellular-and-cholestatic-toxicity
#6
C Aygun, A Y Altınok, A Çakır, A F Agan, Y Balaban
Temozolomide (TMZ) is an oral imidazotetrazine methylating agent which is used for the treatment of glioblastoma multiforme (GBM). We report a case of acute hepatotoxicity in a 53-year old male patient after administration of TMZ for GBM. He had fatigue, nausea, anorexia and jaundice. His laboratory analysis showed alanine aminotransferase(ALT) : 632 IU/L (normal range 0-40) ; aspartate aminotransferase(AST) : 554 IU/L (normal range 5-34) ; alkaline phosphatase(ALP) : 1143 IU/L (normal range 40-150) ; γ-glutamyl transpeptidase(GGT) : 514 IU/L (normal range 9-64 IU/L) ; total bilirubin : 15...
September 2016: Acta Gastro-enterologica Belgica
https://www.readbyqxmd.com/read/28208716/cell-imaging-counting-as-a-novel-ex-vivo-approach-for-investigating-drug-induced-hepatotoxicity-in-zebrafish-larvae
#7
Xuan-Bac Nguyen, Stanislav Kislyuk, Duc-Hung Pham, Angela Kecskés, Jan Maes, Deirdre Cabooter, Pieter Annaert, Peter De Witte, Annelii Ny
Drug-induced liver injury (DILI) is the most common reason for failures during the drug development process and for safety-related withdrawal of drugs from the pharmaceutical market. Therefore, having tools and techniques that can detect hepatotoxic properties in drug candidates at an early discovery stage is highly desirable. In this study, cell imaging counting was used to measure in a fast, straightforward, and unbiased way the effect of paracetamol and tetracycline, (compounds known to cause hepatotoxicity in humans) on the amount of DsRed-labeled hepatocytes recovered by protease digestion from Tg(fabp10a:DsRed) transgenic zebrafish...
February 8, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28208010/circulating-plasma-and-exosomal-micrornas-as-indicators-of-drug-induced-organ-injury-in-rodent-models
#8
Young-Eun Cho, Sang-Hyun Kim, Byung-Heon Lee, Moon-Chang Baek
This study was performed to evaluate whether microRNAs (miRNAs) in circulating exosomes may serve as biomarkers of drug-induced liver, kidney, or muscle-injury. Quantitative PCR analyses were performed to measure the amounts of liver-specific miRNAs (miR-122, miR-192, and miR-155), kidney-specific miR-146a, or muscle-specific miR-206 in plasma and exosomes from mice treated with liver, kidney or muscle toxicants. The levels of liver-specific miRNAs in circulating plasma and exosomes were elevated in acetaminophen-induced liver injury and returned to basal levels by treatment with antioxidant N-acetyl-cysteine...
February 17, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/28192882/ethyl-acetate-fraction-of-pteris-vittata-l-alleviates-2-acetylaminofluorene-induced-hepatic-alterations-in-male-wistar-rats
#9
Paramjeet Kaur, Manish Kumar, Amrit Pal Singh, Satwinderjeet Kaur
Pteris vittata L. commonly called 'Brake Fern' possesses some interesting medicinal properties but its chemopreventive potential largely remains unexplored. Therefore, this study was designed to explore the chemopreventive efficacy of P. vittata L. ethyl acetate fraction (PVEA) against 2-acetylaminofluorene (2-AAF) induced liver toxicity in Wistar rats. Antioxidant activity of PVEA was evaluated using various in vitro antioxidant assays. The protective effects of PVEA were evaluated against 2-acetylaminofluorene (2-AAF) induced hepatic damage in Wistar rats...
February 8, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28192119/leflunomide-induces-nad-p-h-quinone-dehydrogenase-1-enzyme-via-the-aryl-hydrocarbon-receptor-in-neonatal-mice
#10
Amrit Kumar Shrestha, Ananddeep Patel, Renuka T Menon, Weiwu Jiang, Lihua Wang, Bhagavatula Moorthy, Binoy Shivanna
Aryl hydrocarbon receptor (AhR) has been increasingly recognized to play a crucial role in normal physiological homeostasis. Additionally, disrupted AhR signaling leads to several pathological states in the lung and liver. AhR activation transcriptionally induces detoxifying enzymes such as cytochrome P450 (CYP) 1A and NAD(P)H quinone dehydrogenase 1 (NQO1). The toxicity profiles of the classical AhR ligands such as 3-methylcholanthrene and dioxins limit their use as a therapeutic agent in humans. Hence, there is a need to identify nontoxic AhR ligands to develop AhR as a clinically relevant druggable target...
February 10, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28174625/sex-and-age-differences-in-the-expression-of-liver-micrornas-during-the-life-span-of-f344-rats
#11
Joshua C Kwekel, Vikrant Vijay, Tao Han, Carrie L Moland, Varsha G Desai, James C Fuscoe
BACKGROUND: Physiological factors such as age and sex have been shown to be risk factors for adverse effects in the liver, including liver diseases and drug-induced liver injury. Previously, we have reported age- and sex-related significant differences in hepatic basal gene expression in rats during the life span that may be related to susceptibility to such adverse effects. However, the underlying mechanisms of the gene expression changes were not fully understood. In recent years, increasing evidence for epigenetic mechanisms of gene regulation has fueled interest in the role of microRNAs (miRNAs) in toxicogenomics and biomarker discovery...
2017: Biology of Sex Differences
https://www.readbyqxmd.com/read/28165728/hepatoprotective-effect-of-%C3%AF-glutathione-in-a-murine-model-of-acetaminophen-induced-liver-toxicity
#12
Swati S More, Jaime Nugent, Ashish P Vartak, Steffan M Nye, Robert Vince
Ψ-Glutathione (ψ-GSH) is an orally bioavailable and metabolism-resistant glutathione analogue that has been shown previously to substitute glutathione in most of its biochemical roles. Described here in its entirety is the preclinical evaluation of ψ-GSH as a rescue agent for acetaminophen (APAP) overdose: an event where time is of essence. By employing a murine model, four scenarios commonly encountered in emergency medicine are reconstructed. ψ-GSH is juxtaposed against N-acetylcysteine (NAC), the sole clinically available drug, in each of the scenarios...
February 16, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28165393/reduced-sharpin-and-lubac-formation-may-contribute-to-ccl%C3%A2-or-acetaminophen-induced-liver-cirrhosis-in-mice
#13
Takeshi Yamamotoya, Yusuke Nakatsu, Yasuka Matsunaga, Toshiaki Fukushima, Hiroki Yamazaki, Sunao Kaneko, Midori Fujishiro, Takako Kikuchi, Akifumi Kushiyama, Fuminori Tokunaga, Tomoichiro Asano, Hideyuki Sakoda
Linear ubiquitin chain assembly complex (LUBAC), composed of SHARPIN (SHANK-associated RH domain-interacting protein), HOIL-1L (longer isoform of heme-oxidized iron-regulatory protein 2 ubiquitin ligase-1), and HOIP (HOIL-1L interacting protein), forms linear ubiquitin on nuclear factor-κB (NF-κB) essential modulator (NEMO) and induces NF-κB pathway activation. SHARPIN expression and LUBAC formation were significantly reduced in the livers of mice 24 h after the injection of either carbon tetrachloride (CCl₄) or acetaminophen (APAP), both of which produced the fulminant hepatitis phenotype...
February 4, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28163821/the-role-of-cyp2e1-in-the-drug-metabolism-or-bioactivation-in-the-brain
#14
REVIEW
W A García-Suástegui, L A Ramos-Chávez, M Rubio-Osornio, M Calvillo-Velasco, J A Atzin-Méndez, J Guevara, D Silva-Adaya
Organisms have metabolic pathways that are responsible for removing toxic agents. We always associate the liver as the major organ responsible for detoxification of the body; however this process occurs in many tissues. In the same way, as in the liver, the brain expresses metabolic pathways associated with the elimination of xenobiotics. Besides the detoxifying role of CYP2E1 for compounds such as electrophilic agents, reactive oxygen species, free radical products, and the bioactivation of xenobiotics, CYP2E1 is also related in several diseases and pathophysiological conditions...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28155845/design-and-fabrication-of-a-scalable-liver-lobule-on-a-chip-microphysiological-platform
#15
Amin A Banaeiyan, Jannick Theobald, Jurgita Paukštyte, Stefan Wölfl, Caroline B Adiels, Mattias Goksör
The design and fabrication of a very large-scale liver-lobule (VLSLL)-on-a-chip device, providing a microphysiological niche for hepatocytes, is described. The device consists of an integrated network of liver-lobule-like hexagonal tissue-culture chambers constructed in a hybrid layout with a separate seed-feed network. As a key feature, each chamber contains a central outlet mimicking the central vein of a liver lobule. Separating chamber walls located between the culture area and feed network protects cells from the shear force of the convective flow...
February 3, 2017: Biofabrication
https://www.readbyqxmd.com/read/28153389/gold-nanoparticles-ameliorate-acetaminophen-induced-hepato-renal-injury-in-rats
#16
Mohd Salim Reshi, Sadhana Shrivastava, Amita Jaswal, Neelu Sinha, Chhavi Uthra, Sangeeta Shukla
Valuable effects of gold particles have been reported and used in complementary medicine for decades. The aim of this study was to evaluate the therapeutic efficacy of gold nanoparticles (AuNPs) against acetaminophen (APAP) induced toxicity. Albino rats were administered APAP at a dose of 2g/kg p.o. once only. After 24h of APAP intoxication, animals were treated with three different doses of AuNPs (50μg/kg, 100μg/kg, 150μg/kg) orally or silymarin at a dose of 50mg/kg p.o., once only. Animals of all the groups were sacrificed after 24h of last treatment...
January 30, 2017: Experimental and Toxicologic Pathology: Official Journal of the Gesellschaft Für Toxikologische Pathologie
https://www.readbyqxmd.com/read/28153088/specific-and-efficient-regression-of-cancers-harboring-kras-mutation-by-targeted-rna-replacement
#17
Sung Jin Kim, Ju Hyun Kim, Bitna Yang, Jin-Sook Jeong, Seong-Wook Lee
Mutations in the KRAS gene, which persistently activate RAS function, are most frequently found in many types of human cancers. Here, we proposed and verified a new approach against cancers harboring the KRAS mutation with high cancer selectivity and efficient anti-cancer effects based on targeted RNA replacement. To this end, trans-splicing ribozymes from Tetrahymena group I intron were developed, which can specifically target and reprogram the mutant KRAS G12V transcript to induce therapeutic gene activity in cells...
February 1, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28152447/astaxanthin-pretreatment-attenuates-acetaminophen-induced-liver-injury-in-mice
#18
Jingyao Zhang, Simin Zhang, Jianbin Bi, Jingxian Gu, Yan Deng, Chang Liu
BACKGROUND: Acetaminophen (APAP) is a conventional drug widely used in the clinic because of its antipyretic-analgesic effects. However, accidental or intentional APAP overdoses induce liver injury and even acute liver failure (ALF). Astaxanthin (ASX) is the strongest antioxidant in nature that shows preventive and therapeutic properties, such as ocular protection, anti-tumor, anti-diabetes, anti-inflammatory, and immunomodulatory effects. The aim of present study was to determine whether ASX pretreatment provides protection against APAP-induced liver failure...
January 31, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28150517/human-biology-based-drug-safety-evaluation-scientific-rationale-current-status-and-future-challenges
#19
J Gerry Kenna
Animal toxicity studies used to assess the safety of new candidate pharmaceuticals prior to their progression into human clinical trials are unable to assess the risk of non-pharmacologically mediated idiosyncratic adverse drug reactions (ADRs), the most frequent of which are drug-induced liver injury and cardiotoxicity. Idiosyncratic ADRs occur only infrequently and in certain susceptible humans, but are caused by many hundreds of different drugs and may lead to serious illness. Areas covered: Idiosyncratic ADRs are initiated by drug-related chemical insults, which cause toxicity due to susceptibility factors that manifest only in certain patients...
February 2, 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28139008/oxidative-stress-mediated-developmental-toxicity-induced-by-isoniazide-in-zebrafish-embryos-and-larvae
#20
Yu Zou, Yun Zhang, Liwen Han, Qiuxia He, Hairong Hou, Jian Han, Ximin Wang, Chengyun Li, Juan Cen, Kechun Liu
Isoniazide (INH) is an important first-line drug that is used to treat tuberculosis. However, the effect of INH on fetal growth has not yet been elucidated, and the mechanism of INH-induced developmental toxicity is still unknown. In the present study, we employed zebrafish embryos and larvae to investigate the developmental toxicity of INH. The survival rates of the embryos and larvae as well as the hatching rates of embryos were significantly reduced. Morphological abnormalities, including spinal curvature, yolk retention, swimming bladder absence, tail bending and shorter body lengths were induced by INH...
January 31, 2017: Journal of Applied Toxicology: JAT
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