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hepatotoxic drugs

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https://www.readbyqxmd.com/read/28217372/psychotropic-drugs-and-liver-disease-a-critical-review-of-pharmacokinetics-and-liver-toxicity
#1
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/28216958/-1-h-nmr-based-serum-metabolomics-reveals-erythromycin-induced-liver-toxicity-in-albino-wistar-rats
#2
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/28215634/isolation-and-expansion-of-human-pluripotent-stem-cell-derived-hepatic-progenitor-cells-by-growth-factor-defined-serum-free-culture-conditions
#3
Takayuki Fukuda, Kazuo Takayama, Mitsuhi Hirata, Yu-Jung Liu, Kana Yanagihara, Mika Suga, Hiroyuki Mizuguchi, Miho K Furue
Limited growth potential, narrow ranges of sources, and difference in variability and functions from batch to batch of primary hepatocytes cause a problem for predicting drug-induced hepatotoxicity during drug development. Human pluripotent stem cell (hPSC)-derived hepatocyte-like cells in vitro are expected as a tool for predicting drug-induced hepatotoxicity. Several studies have already reported efficient methods for differentiating hPSCs into hepatocyte-like cells, however its differentiation process is time-consuming, labor-intensive, cost-intensive, and unstable...
February 16, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28214545/potential-of-amphiphilic-graft-copolymer-%C3%AE-tocopherol-succinate-g-carboxymethyl-chitosan-in-modulating-the-permeability-and-anticancer-efficacy-of-tamoxifen
#4
Sunil K Jena, Sanjaya K Samal, Shamandeep Kaur, Mahesh Chand, Abhay T Sangamwar
Recent studies showed an enhanced oral bioavailability of tamoxifen (TMX) by hydrophobically modified α-tocopherol succinate-g-carboxymethyl chitosan (Cmc-TS) micelles. As a continued effort, here we evaluated TMX-loaded polymeric micelles (TMX-PMs) for its enhanced permeability with increased anticancer efficacy and decreased hepatotoxicity. We employed co-solvent evaporation technique to encapsulate TMX into Cmc-TS. Apparent permeability assay of TMX-PMs was performed on Caco-2 cell line. The absorptive transport of TMX increased significantly about 3...
February 16, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28214329/-p-clphse-2-reduces-hepatotoxicity-induced-by-monosodium-glutamate-by-improving-mitochondrial-function-in-rats
#5
Caroline B Quines, Pietro M Chagas, Diane Hartmann, Nélson R Carvalho, Félix A Soares, Cristina W Nogueira
It is has been demonstrated that mitochondrial dysfunction, oxidative stress and chronic inflammatory process are associated with progress of morbid obesity in human patients. For this reason, the searching for safe and effective antiobesity drugs has been the subject of intense research. In this context, the organic selenium compounds have attracted much attention due to their pharmacological properties, such as antihyperglycemic, antioxidant and anti-inflammatory. The aim of this study was to evaluate the hepatoprotective action of p-chloro-diphenyl diselenide (p-ClPhSe)2 , an organic selenium compound, in a model of obesity induced by monosodium glutamate (MSG) administration in rats...
February 18, 2017: Journal of Cellular Biochemistry
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/28208250/simultaneous-voltammetric-determination-of-acetaminophen-and-isoniazid-hepatotoxicity-related-drugs-utilizing-bismuth-oxide-nanorod-modified-screen-printed-electrochemical-sensing-platforms
#8
Bahaa G Mahmoud, Mohamed Khairy, Farouk A Rashwan, Craig E Banks
To overcome the recent outbreaks of hepatotoxicity-related drugs, a new analytical tool for the continuously determination of these drugs in human fluids is required. Electrochemical-based analytical methods offer an effective, rapid, and simple tool for on-site determination of various organic and inorganic species. However, the design of a sensitive, selective, stable, and reproducible sensor is still a major challenge. In the present manuscript, a facile, one-pot hydrothermal synthesis of bismuth oxide (Bi2O2...
February 7, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28196344/identification-characterization-and-in-silico-admet-prediction-of-roflumilast-degradation-products
#9
Mariana S Pinheiro, Gil M Viana, Bárbara de A Abrahim Vieira, Alessandra Mendonça Teles de Souza, Carlos Rangel Rodrigues, Rita de Cássia E E Marins, Lúcio M Cabral, Valéria P de Sousa
The present study reports the degradation behavior of roflumilast (RFL), a new drug developed for the treatment of chronic obstructive pulmonary disease. The degradation of RFL was tested under various stress conditions as per the guidelines of the International Conference on Harmonization. The degradation products (DPs) of RFL were identified, characterized and in silico predictions were made of their pharmacokinetic properties, absorption, distribution, metabolism, excretion and toxicity (ADMET). RFL was subjected to various stress conditions including photodegradation, alkaline and acidic hydrolysis, oxidative and metallic degradation...
February 6, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28188357/analgesic-antiallodynic-and-anticonvulsant-activity-of-novel-hybrid-molecules-derived-from-n-benzyl-2-2-5-dioxopyrrolidin-1-yl-propanamide-and-2-2-5-dioxopyrrolidin-1-yl-butanamide-in-animal-models-of-pain-and-epilepsy
#10
Anna Rapacz, Krzysztof Kamiński, Jolanta Obniska, Paulina Koczurkiewicz, Elżbieta Pękala, Barbara Filipek
The purpose of the present study was to examine the analgesic activity of six novel hybrid molecules, which demonstrated in the previous research anticonvulsant activity in the maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole seizure (scPTZ) tests in mice. The antinociceptive properties were estimated in three models of pain in mice-the hot plate test, the formalin test, and in the oxaliplatin-induced neuropathy. Moreover, extended anticonvulsant studies were carried out and the antiseizure activity was investigated in the 6-Hz test...
February 10, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28188341/evaluation-of-transcriptomic-signature-as-a-valuable-tool-to-study-drug-induced-cholestasis-in-primary-human-hepatocytes
#11
Céline Parmentier, Philippe Couttet, Armin Wolf, Thomas Zaccharias, Bruno Heyd, Philippe Bachellier, Marianne Uteng, Lysiane Richert
Primary human hepatocyte (PHH) sandwich cultures from five different donors were daily exposed to cyclosporine A (CsA), ibuprofen (IBU), chlorpromazine (CPZ), amiodarone (AMI) and paracetamol (APAP) at their respective Cmax (total) for short-term (1-3 days) and long-term treatment (14 days). Whole genome mRNA profiles (34,693 genes in total) were conducted using an Illumina microarray platform. The impact of compound treatments on gene signatures involved in liver differentiation, cholestasis and in bile acid homeostasis was evaluated...
February 10, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28175170/p649-does-switching-to-low-dose-thiopurine-and-allopurinol-prevent-ibd-patients-with-evidence-of-hypermethylation-on-standard-dose-thiopurines-from-developing-hepatotoxicity-and-drug-side-effects
#12
K Wade, H Johnson, K Slinger, C Hovell, S Weaver, S McLaughlin
No abstract text is available yet for this article.
February 1, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/28168347/local-and-systemic-diffusion-of-antineoplastic-drugs-following-vertebroplasty-using-acrylic-cement-mixed-with-cisplatin-or-methotrexate-experimental-study-in-pigs
#13
Rafael Llombart-Blanco, Carlos Villas, Álvaro Silva, Azucena Aldaz, Iñigo Navarro, Jeronimo Forteza, Salvador Martin Algarra, Matías Alfonso
PURPOSE: To determine the efficacy of cisplatin- or methotrexate-containing acrylic cement for local and systemic antineoplastic drug diffusion. Among the uses of acrylic cement or Polymethylmethacrylate (PMMA), there is the possibility to employ it as vehicle for drug diffusion. This capability is of interest in the treatment of pathological fractures: The curative effects of the cement (cytotoxicity of the monomer and increased temperature) are added to the antineoplastic effect of the drugs...
February 6, 2017: European Spine Journal
https://www.readbyqxmd.com/read/28165437/relationship-of-recovered-hepatitis-b-infection-with-appearance-of-toxic-propylthiouracil-hepatitis
#14
Lejla Čalkić, Lejla Bajramović-Omeragić
Aim To investigate the relationship between recovered hepatitis B infection with appearance of toxic propylthiouracil (PTU) hepatitis and point out the growing importance of the use of drugs in the development of hepatitis. Methods A case of a 45-year-old female patient with suspicion of acute viral hepatitis who had polypragmasy of drugs in the last ten years, due to the polymorphism of symptoms/illnesses (diabetes mellitus, depression, hypertension, hypothyroidism) was presented. Results A female patient had hyperthyroidism after resolved viral hepatitis B with HBsAg seroconversion (HBsAg negative, antiHBs positive)...
February 1, 2017: Medicinski Glasnik
https://www.readbyqxmd.com/read/28156176/respirable-controlled-release-polymeric-colloid-rcrpc-of-bosentan-for-the-management-of-pulmonary-hypertension-in-vitro-aerosolization-histological-examination-and-in-vivo-pulmonary-absorption
#15
Lydia A Hanna, Emad B Basalious, Omaima N ELGazayerly
Bosentan is an endothelin receptor antagonist (ERA) prescribed for patients with pulmonary arterial hypertension (PAH). The oral delivery of bosentan possesses several drawbacks such as low bioavailability (about 50%), short duration of action, frequent administration, hepatotoxicity and systemic hypotension. The pulmonary administration would circumvent the pre-systemic metabolism thus improving the bioavailability and avoids the systemic adverse effects of oral bosentan. However, the short duration of action and the frequent administration are the major drawbacks of inhalation therapy...
November 2016: Drug Delivery
https://www.readbyqxmd.com/read/28152447/astaxanthin-pretreatment-attenuates-acetaminophen-induced-liver-injury-in-mice
#16
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/28151932/a-comparative-analysis-of-drug-induced-hepatotoxicity-in-clinically-relevant-situations
#17
Christoph Thiel, Henrik Cordes, Lorenzo Fabbri, Hélène Eloise Aschmann, Vanessa Baier, Ines Smit, Francis Atkinson, Lars Mathias Blank, Lars Kuepfer
Drug-induced toxicity is a significant problem in clinical care. A key problem here is a general understanding of the molecular mechanisms accompanying the transition from desired drug effects to adverse events following administration of either therapeutic or toxic doses, in particular within a patient context. Here, a comparative toxicity analysis was performed for fifteen hepatotoxic drugs by evaluating toxic changes reflecting the transition from therapeutic drug responses to toxic reactions at the cellular level...
February 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28144825/a-transcriptomic-study-suggesting-human-ipsc-derived-hepatocytes-potentially-offer-a-better-in-vitro-model-of-hepatotoxicity-than-most-hepatoma-cell-lines
#18
Xiugong Gao, Yitong Liu
Hepatocytes derived from human induced pluripotent stem cells (iPSCs) hold great promise as an in vitro liver model by virtue of their unlimited long-term supply, stability and consistency in functionality, and affordability of donor diversity. However, the suitability of iPSC-derived hepatocytes (iPSC-Heps) for toxicology studies has not been fully validated. In the current study, we characterized global gene expression profiles of iPSC-Heps in comparison to those of primary human hepatocytes (PHHs) and several human hepatoma cell lines (HepaRG, HuH-7, HepG2, and HepG2/C3A)...
January 31, 2017: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/28138970/prediction-of-drug-induced-liver-injury-using-keratinocytes
#19
Rika Hirashima, Tomoo Itoh, Robert H Tukey, Ryoichi Fujiwara
Drug-induced liver injury (DILI) is one of the most common adverse drug reactions. DILI is often accompanied by skin reactions, including rash and pruritus. However, it is still unknown whether DILI-associated genes such as S100 calcium-binding protein A and interleukin (IL)-1β are involved in drug-induced skin toxicity. In the present study, most of the tested hepatotoxic drugs such as pioglitazone and diclofenac induced DILI-associated genes in human and mouse keratinocytes. Keratinocytes of mice at higher risk for DILI exhibited an increased IL-1β basal expression...
January 31, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/28138249/propylthiouracil-induced-liver-failure-and-artificial-liver-support-systems-a-case-report-and-review-of-the-literature
#20
Dong-Bo Wu, En-Qiang Chen, Lang Bai, Hong Tang
BACKGROUND: Antithyroid drugs carry a potential risk of hepatotoxicity. Propylthiouracil (PTU) is commonly prescribed for patients with hyperthyroidism. PTU, however, can induce liver injury, ranging from mild asymptomatic elevation of aminotransferases to acute liver failure (ALF). CASE PRESENTATION: This case reports on a 16-year-old Chinese girl with hyperthyroidism, who was admitted to our hospital for jaundice, nausea, and fatigue associated with severe hyperbilirubinemia and coagulopathy...
2017: Therapeutics and Clinical Risk Management
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