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https://www.readbyqxmd.com/read/28935499/hepatotoxicity-of-fusariotoxins-alone-and-in-combination-towards-the-heparg-human-hepatocyte-cell-line
#1
Marie-Caroline Smith, Nolwenn Hymery, Samuel Troadec, Audrey Pawtowski, Emmanuel Coton, Stéphanie Madec
While the reality of mycotoxin co-occurrence in food commodities is now established, their effects in mixtures are not well studied. The present study investigated the individual and combined effects of deoxynivalenol (DON), nivalenol (NIV), T-2 toxin (T2), fumonisin B1 (FB1), zearalenone (ZEA) and moniliformin (MON) fusariotoxins on cell viability and cell death mechanisms in proliferating HepaRG cells, a human derived liver cell line. In addition, DON-ZEA being one of the most widespread mycotoxin mixtures in grains worldwide, its effect on the expression levels of genes encoding for sets of hepatocyte-specific functions was studied...
September 18, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28934748/severe-drug-induced-liver-injury-as-an-adverse-drug-event-of-antibiotics-a-case-report-and-review-of-the-literature
#2
Martin Munz, Hans Grummich, Josef Birkmann, Martin Wilhelm, Ulrike Holzgrabe, Fritz Sörgel
Drug-induced liver injury is one of the main reasons for acute liver failure. We report the case of a young patient who experienced a drug-induced liver injury resulting in life-threatening acute liver failure after treatment with different antibiotics (amoxicillin, ciprofloxacin, cefazolin, clindamycin) and acetaminophen, or a combination of these drugs. Moreover, we provide an overview of the hepatotoxic potential of these drugs.
September 22, 2017: Chemotherapy
https://www.readbyqxmd.com/read/28934241/hla-dr7-and-hla-dq2-transgenic-mouse-strains-tested-as-a-model-system-for-ximelagatran-hepatotoxicity
#3
Hanna Lundgren, Klara Martinsson, Karin Cederbrant, Johan Jirholt, Daniel Mucs, Katja Madeyski-Bengtson, Said Havarinasab, Per Hultman
The oral thrombin inhibitor ximelagatran was withdrawn in the late clinical trial phase because it adversely affected the liver. In approximately 8% of treated patients, drug-induced liver injury (DILI) was expressed as transient alanine transaminase (ALT) elevations. No evidence of DILI had been revealed in the pre-clinical in vivo studies. A whole genome scan study performed on the clinical study material identified a strong genetic association between the major histocompatibility complex alleles for human leucocyte antigens (HLA) (HLA-DR7 and HLA-DQ2) and elevated ALT levels in treated patients...
2017: PloS One
https://www.readbyqxmd.com/read/28932197/antiplasmodial-activity-and-toxicological-assessment-of-curcumin-plga-encapsulated-nanoparticles
#4
Zulaikha A Busari, Kabiru A Dauda, Olajumoke A Morenikeji, Funmilayo Afolayan, Oyetunde T Oyeyemi, Jairam Meena, Debasis Sahu, Amulya K Panda
Curcumin is a polyphenolic pigment isolated from the rhizomes of Curcuma longa (turmeric), a medicinal plant widely used in the ancient Indian and Chinese medicine. The antiplasmodial activity of curcumin is often hampered by its fast metabolism and poor water solubility, thus its incorporation into a delivery system could circumvent this problem. This study aimed to evaluate the in vivo antiplasmodial activity and the toxicity assessment of curcumin incorporated into poly (lactic-co-glycolic) acid (PLGA) nanoparticles...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28919358/perfused-human-hepatocyte-microtissues-identify-reactive-metabolite-forming-and-mitochondria-perturbing-hepatotoxins
#5
Cliff Rowe, Mohsen Shaeri, Emma Large, Terri Cornforth, Angela Robinson, Tomasz Kostrzewski, Rowena Sison-Young, Christopher Goldring, Kevin Park, David Hughes
Hepatotoxins cause liver damage via many mechanisms but the formation of reactive metabolites and/or damage to liver mitochondria are commonly implicated. We assess 3D human primary hepatocyte microtissues as a platform for hepatotoxicity studies with reactive metabolite-forming and mitochondria-perturbing compounds. We show that microtissues formed from cryopreserved human hepatocytes had bile canaliculi, transcribed mRNA from genes associated with xenobiotic metabolism and expressed functional cytochrome P450 enzymes...
September 15, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28918038/strategies-for-in%C3%A2-vivo-screening-and-mitigation-of-hepatotoxicity-associated-with-antisense-drugs
#6
Piotr J Kamola, Klio Maratou, Paul A Wilson, Kay Rush, Tanya Mullaney, Tom McKevitt, Paula Evans, Jim Ridings, Probash Chowdhury, Aude Roulois, Ann Fairchild, Sean McCawley, Karen Cartwright, Nigel J Gooderham, Timothy W Gant, Kitty Moores, Stephen A Hughes, Mark R Edbrooke, Kenneth Clark, Joel D Parry
Antisense oligonucleotide (ASO) gapmers downregulate gene expression by inducing enzyme-dependent degradation of targeted RNA and represent a promising therapeutic platform for addressing previously undruggable genes. Unfortunately, their therapeutic application, particularly that of the more potent chemistries (e.g., locked-nucleic-acid-containing gapmers), has been hampered by their frequent hepatoxicity, which could be driven by hybridization-mediated interactions. An early de-risking of this liability is a crucial component of developing safe, ASO-based drugs...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28912805/antifibrotic-effect-of-lactulose-on-a-methotrexate-induced-liver-injury-model
#7
Banu Taskin, Mümin Alper Erdoğan, Gürkan Yiğittürk, Damla Günenç, Oytun Erbaş
The most severe side effect of prolonged MTX treatment is hepatotoxicity. The aim of this study is to investigate the effect of lactulose treatment on MTX-induced hepatotoxicity in a rat model. Twenty-four male rats were included in the study. Sixteen rats were given a single dose of 20 mg/kg MTX to induce liver injury. Eight rats were given no drugs. 16 MTX-given rats were divided into two equal groups. Group 1 subjects were given lactulose 5 g/kg/day, and group 2 subjects were given saline 1 ml/kg/day for 10 days...
2017: Gastroenterology Research and Practice
https://www.readbyqxmd.com/read/28911608/effect-of-goat-milk-on-hepatotoxicity-induced-by-antitubercular-drugs-in-rats
#8
Sonam Miglani, Rakesh Raman Patyar, Sazal Patyar, Mohammad Rafi Reshi
Aim of the present study was to assess the hepatoprotective activity of goat milk on antitubercular drug-induced hepatotoxicity in rats. Hepatotoxicity was induced in rats using a combination of isoniazid, rifampicin, and pyrazinamide given orally as a suspension for 30 days. Treatment groups received goat milk along with antitubercular drugs. Liver damage was assessed using biochemical and histological parameters. Administration of goat milk (20 mL/kg) along with antitubercular drugs (Group III) reversed the levels of serum alanine aminotransferase (82 ± 25...
October 2016: Journal of Food and Drug Analysis
https://www.readbyqxmd.com/read/28904294/assessment-of-amiodarone-induced-phospholipidosis-in-chimeric-mice-with-a-humanized-liver
#9
Seigo Sanoh, Yuto Yamachika, Yuka Tamura, Yaichiro Kotake, Yasumi Yoshizane, Yuji Ishida, Chise Tateno, Shigeru Ohta
It is important to consider susceptibility to drug-induced toxicity between animals and humans. Chimeric mice with a humanized liver are expected to predict hepatotoxicity in humans. Drug-induced phospholipidosis (DIPL), in which phospholipids accumulate, is a known entity. In this study, we examined whether chimeric mice can reveal species differences in DIPL. Changes in various phosphatidylcholine (PhC) molecules were investigated in the liver of chimeric mice after administering amiodarone, which induces phospholipidosis...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28900877/genetic-polymorphisms-of-slco1b1-cyp2e1-and-ugt1a1-and-susceptibility-to-anti-tuberculosis-drug-induced-hepatotoxicity-a-chinese-population-based-prospective-case-control-study
#10
Qin Sun, Hai-Peng Liu, Rui-Juan Zheng, Peng Wang, Zhi-Bin Liu, Wei Sha, He-Ping Xiao
BACKGROUND: Drug transporters and drug-metabolizing enzymes have been linked to drug-induced hepatotoxicity. Solute carrier organic anion transporter family member 1B1 (SLCO1B1), cytochrome P450 2E1 (CYP2E1), and UDP glucuronosyltransferase 1A1 (UGT1A1) were selected as candidate genes to explore their association with susceptibility to anti-tuberculosis drug-induced hepatotoxicity (ATDH). METHODS: Thirty-four tag single nucleotide polymorphisms (tagSNPs) in SLCO1B1, CYP2E1, and UGT1A1 with 10-kb expansion up- and down-stream were genotyped in 461 patients with ATDH and 466 patients without ATDH in a prospective 1:1 matched case-control study...
September 12, 2017: Clinical Drug Investigation
https://www.readbyqxmd.com/read/28887915/hepatoprotective-naphthalene-diglucoside-from-neanotis-wightiana-aerial-parts
#11
Niranjan Das, Atanas G Atanasov, Prashanta Kumar Deb, Andrei Mocan, Seyed Mohammad Nabavi, Ranjib Ghosh, Biswanath Dinda
BACKGROUND: Neanotis wightiana (Wall. ex Wight & Arn) W.H. Lewis has been used in traditional medicine in India for the treatment of liver disorders. In fact, this plant is frequently used by the local people of Tripura for the treatment of liver disorder problems. In previous study on this plant we have isolated a hepatoprotective saponin, neanoside A. PURPOSE: Evaluation of in vivo hepatoprotective effects of isolated compounds from N. wightiana aerial parts on serum hepatic-biomarkers in CCl4- induced hepatotoxicity in rats to validate the traditional use of the plant...
September 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28878340/the-pharmacogenomics-of-valproic-acid
#12
REVIEW
Miao-Miao Zhu, Hui-Lan Li, Li-Hong Shi, Xiao-Ping Chen, Jia Luo, Zan-Ling Zhang
Valproic acid is an anticonvulsant and mood-stabilizing drug used primarily in the treatment of epilepsy and bipolar disorder. Adverse effects of valproic acid are rare, but hepatotoxicity is severe in particular in those younger than 2 years old and polytherapy. During valproic acid treatment, it is difficult for prescribers to predict its individual response. Recent advances in the field of pharmacogenomics have indicated variants of candidate genes that affect valproic acid efficacy and safety. In this review, a large number of candidate genes that influence valproic acid pharmacokinetics and pharmacodynamics are discussed, including metabolic enzymes, drug transporters, neurotransmitters and drug targets...
September 7, 2017: Journal of Human Genetics
https://www.readbyqxmd.com/read/28878168/metabolomics-analysis-of-urine-samples-from-children-after-acetaminophen-overdose
#13
Laura K Schnackenberg, Jinchun Sun, Sudeepa Bhattacharyya, Pritmohinder Gill, Laura P James, Richard D Beger
Acetaminophen (APAP), a commonly used over-the-counter analgesic, accounts for approximately fifty percent of the cases of acute liver failure (ALF) in the United States due to overdose, with over half of those unintentional. Current clinical approaches for assessing APAP overdose rely on identifying the precise time of overdose and quantitating acetaminophen alanine aminotransferase (ALT) levels in peripheral blood. Novel specific and sensitive biomarkers may provide additional information regarding patient status post overdose...
September 6, 2017: Metabolites
https://www.readbyqxmd.com/read/28875055/pilot-algorithm-designed-to-help-early-detection-of-hmg-coa-reductase-inhibitor-induced-hepatotoxicity
#14
Joo Young Hong, Hun-Sung Kim, In Young Choi
OBJECTIVES: To enable early detection of adverse drug reactions (ADRs) in patients using HMG-CoA reductase inhibitors (statins), we developed an algorithm that automatically detects liver injury caused by statins from Electronic Medical Record (EMR) data. We verified the performance of our algorithm through manual ADR assessment and a direct chart review. METHODS: The subjects in this study were patients who had been prescribed a statin for the first time among outpatients in Seoul St...
July 2017: Healthcare Informatics Research
https://www.readbyqxmd.com/read/28873351/frequency-and-pathological-characteristics-of-drug-induced-liver-injury-in-a-tertiary-medical-center
#15
Mark Ettel, Gabriel Acosta Gonzalez, Shweta Gera, Ogechukwu Eze, Samuel Sigal, James S Park, Ruliang Xu
Drug-induced liver injury (DILI) accounts for approximately 10% of acute hepatitis cases. DILI can arise as idiosyncratic or intrinsic injury from hundreds of drugs, herbals, and nutritional supplements and is essential to recognize as one of the differential diagnoses of hepatitis in a liver biopsy. The purpose of this study is to investigate the frequency and pathological characteristics of DILI related to the variety of hepatotoxic agents. We searched our pathology database for all patients with hepatitis diagnosed on liver biopsy from January 2012 to May 2016, and selected patients with a diagnosis of DILI...
September 2, 2017: Human Pathology
https://www.readbyqxmd.com/read/28869866/synergistic-antitumor-effect-mediated-by-a-paclitaxel-conjugated-polymeric-micelle-coated-oncolytic-adenovirus
#16
Dayananda Kasala, Soo-Hwan Lee, Jin Woo Hong, Joung-Woo Choi, Kihoon Nam, Yoon Ho Chung, Sung Wan Kim, Chae-Ok Yun
Combination treatment consisting of oncolytic adenovirus (Ad) and paclitaxel (PTX) is a promising strategy to achieve synergistic antitumor effect. However, a co-administration approach is subject to inherent limitations due to the poor solubility of PTX and chemoresistance of tumor cells. In order to overcome these limitations, an oncolytic Ad expressing a p53 variant (oAd-vp53) that is resistant to p53 inactivation in the tumor microenvironment was complexed with PEGylated and PTX-conjugated polymeric micelle (APP)...
August 23, 2017: Biomaterials
https://www.readbyqxmd.com/read/28867490/theoretical-evaluation-of-admet-properties-for-coumarin-derivatives-as-compounds-with-therapeutic-potential
#17
Teresa Żołek, Dorota Maciejewska
Coumarins have received a considerable attention in the last three decades as the lead structures for the discovery of orally administrated chemotherapeutics. Despite of the large amounts of in vitro activity information, relatively a little is known about their bioavailability in vivo. This paper presents an evaluation of drug-likeness of 31 coumarin derivatives on the basis of Lipinski's rule of five, and computed ADMET parameters (adsorption, distribution, metabolism, elimination and toxicity). Nine compounds which were predicted as showing the cardiotoxicity, were examined as hERG K(+) channel blockers using in silico approach...
September 1, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28865237/dose-dependent-acute-liver-injury-with-hypersensitivity-features-in-humans-due-to-a-novel-microsomal-prostaglandin-e-synthase-1-inhibitor
#18
Yan Jin, Arie Regev, Jeanelle Kam, Krista Phipps, Claire Smith, Judith Henck, Kristina Campanale, Leijun Hu, D Greg Hall, Xiao Yan Yang, Masako Nakano, Terry Ann McNearney, Jack Uetrecht, William Landschulz
AIM: LY3031207, a novel microsomal prostaglandin E synthase 1 inhibitor, was evaluated in a multiple ascending dose study after nonclinical toxicology studies and a single ascending dose study demonstrated an acceptable toxicity, safety, and tolerability profile. METHODS: Healthy subjects were randomised to receive LY3031207 (25, 75, and 275 mg), placebo, or celecoxib (400 mg) once daily for 28 days. The safety, tolerability, and pharmacokinetic and pharmacodynamic profiles of LY3031207 were evaluated...
September 2, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28864554/dietary-supplements-isotretinoin-and-liver-toxicity-in-adolescents-a-retrospective-case-series
#19
Cynthia Marie Carver DeKlotz, Keith D Roby, Sheila Fallon Friedlander
Isotretinoin is the most effective acne therapy available, but has the potential for a number of adverse side effects, including transaminitis. The iPLEDGE isotretinoin program recommends avoiding some herbals and supplements due to potential side effects. However, little is known about the effects of protein supplements on the liver, particularly in patients taking isotretinoin. We designed a retrospective chart review to evaluate the symptoms, diagnosis, treatment, and outcome of patients on or preparing to take isotretinoin therapy who were concurrently ingesting protein or herbal supplementation and who developed transaminitis...
September 1, 2017: Pediatrics
https://www.readbyqxmd.com/read/28861933/desmosterol-accumulation-in-users-of-amiodarone
#20
Piia Simonen, Jukka Lehtonen, Anna-Maija Lampi, Vieno Piironen, Ulf-Håkan Stenman, Markku Kupari, Helena Gylling
BACKGROUND: Amiodarone is an effective and widely used antiarrhythmic drug with many possible adverse effects including hypercholesterolemia and hepatotoxicity. OBJECTIVE: Our aim was to evaluate how long-term amiodarone treatment affects cholesterol metabolism. METHODS: The study population consisted of 56 cardiac patients, of whom 20 were on amiodarone (amiodarone + group) and 36 did not use the drug (amiodarone - group). We also studied a control group of 124 individuals selected randomly from the population...
September 1, 2017: Journal of Internal Medicine
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