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drug induced liver toxicity

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https://www.readbyqxmd.com/read/29771932/a-multi-center-preclinical-study-of-gadoxetate-dce-mri-in-rats-as-a-biomarker-of-drug-induced-inhibition-of-liver-transporter-function
#1
Anastassia Karageorgis, Stephen C Lenhard, Brittany Yerby, Mikael F Forsgren, Serguei Liachenko, Edvin Johansson, Mark A Pilling, Richard A Peterson, Xi Yang, Dominic P Williams, Sharon E Ungersma, Ryan E Morgan, Kim L R Brouwer, Beat M Jucker, Paul D Hockings
Drug-induced liver injury (DILI) is a leading cause of acute liver failure and transplantation. DILI can be the result of impaired hepatobiliary transporters, with altered bile formation, flow, and subsequent cholestasis. We used gadoxetate dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), combined with pharmacokinetic modelling, to measure hepatobiliary transporter function in vivo in rats. The sensitivity and robustness of the method was tested by evaluating the effect of a clinical dose of the antibiotic rifampicin in four different preclinical imaging centers...
2018: PloS One
https://www.readbyqxmd.com/read/29765215/in-vivo-investigation-on-the-chronic-hepatotoxicity-induced-by-intraperitoneal-administration-of-10-nm-silicon-dioxide-nanoparticles
#2
Mansour Almansour, Saud Alarifi, Bashir Jarrar
Background: Silicon dioxide (silica) nanoparticles (SDNPs) are widely used in nanotechnology and medicine, but these nanomaterials may carry a high risk for human health while little is known about their toxicity. Methods: We investigated the alterations in morphometry, biochemistry, hematology, histology of liver tissue and gene expression of drug-metabolizing enzymes induced by 10-nm SDNPs. Healthy male Wistar albino rats were exposed to 20, 35 and 50 repeated injections of SDNPs (2 mg/kg body weight)...
2018: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/29761207/omics-based-responses-induced-by-bosentan-in-human-hepatoma-heparg-cell-cultures
#3
Robim M Rodrigues, Laxmikanth Kollipara, Umesh Chaudhari, Agapios Sachinidis, René P Zahedi, Albert Sickmann, Annette Kopp-Schneider, Xiaoqi Jiang, Hector Keun, Jan Hengstler, Marlies Oorts, Pieter Annaert, Eef Hoeben, Eva Gijbels, Joery De Kock, Tamara Vanhaecke, Vera Rogiers, Mathieu Vinken
Bosentan is well known to induce cholestatic liver toxicity in humans. The present study was set up to characterize the hepatotoxic effects of this drug at the transcriptomic, proteomic, and metabolomic levels. For this purpose, human hepatoma-derived HepaRG cells were exposed to a number of concentrations of bosentan during different periods of time. Bosentan was found to functionally and transcriptionally suppress the bile salt export pump as well as to alter bile acid levels. Pathway analysis of both transcriptomics and proteomics data identified cholestasis as a major toxicological event...
May 14, 2018: Archives of Toxicology
https://www.readbyqxmd.com/read/29760366/-contribution-of-chimeric-mice-with-a-humanized-liver-to-the-evaluation-of-pharmacology-toxicity-and-pharmacokinetics-in-drug-discovery-and-development
#4
Seigo Sanoh, Shigeru Ohta
To develop new drugs with high efficacy and safety, it is important to predict the pharmacological, toxicological, and pharmacokinetic profiles of drug candidates in humans. Chimeric mice with a humanized liver are mice in which human hepatocytes have been transplanted, such that mouse liver cells are replaced with human hepatocytes; these mice have been used as prediction models. Studies performed thus far indicate that chimeric mice with a humanized liver can be used for the prediction of human-specific metabolite formation and plasma concentration-time curves for several drugs...
2018: Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica
https://www.readbyqxmd.com/read/29755963/environmental-toxin-screening-using-human-derived-3d-bioengineered-liver-and-cardiac-organoids
#5
Steven D Forsythe, Mahesh Devarasetty, Thomas Shupe, Colin Bishop, Anthony Atala, Shay Soker, Aleksander Skardal
Introduction: Environmental toxins, such as lead and other heavy metals, pesticides, and other compounds, represent a significant health concern within the USA and around the world. Even in the twenty-first century, a plethora of cities and towns in the U.S. have suffered from exposures to lead in drinking water or other heavy metals in food or the earth, while there is a high possibility of further places to suffer such exposures in the near future. Methods: We employed bioengineered 3D human liver and cardiac organoids to screen a panel of environmental toxins (lead, mercury, thallium, and glyphosate), and charted the response of the organoids to these compounds...
2018: Frontiers in Public Health
https://www.readbyqxmd.com/read/29753871/combinatorial-usage-of-fungal-polysaccharides-from-cordyceps-sinensis-and-ganoderma-atrum-ameliorate-drug-induced-liver-injury-in-mice
#6
Songtao Fan, Xiaojun Huang, Sunan Wang, Chang Li, Zhihong Zhang, Mingyong Xie, Shaoping Nie
This study investigated the possible protective effect of combined fungal polysaccharides (CFP), consisting of Cordyceps sinensis polysaccharides (CSP) and Ganoderma atrum polysaccharides (PSG) with well-defined structural characteristics, against cyclophosphamide (CTX)-induced hepatotoxicity in mice. Our results indicated CFP effectively prevented the liver injury by decreasing toxicity markers (aspartate transaminase, alanine aminotransferase and alkaline phosphatase). Further biochemical and molecular analysis indicated CSP particularly inhibited the activation of Toll-like receptor 9 (TLR9) and its related inflammatory signals, including pro-inflammatory cytokines, inducible nitric oxide synthase, and cyclooxygenase-2 to modulate hepatic inflammation response...
May 10, 2018: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29753739/effect-of-cisplatin-on-the-clock-genes-expression-in-the-liver-heart-and-kidney
#7
Bei-Bei Cao, Dengfeng Li, Xiaoliang Xing, Yaguang Zhao, Kunyang Wu, Fang Jiang, Wei Yin, Jia-Da Li
Cisplatin is a platinum-based chemotherapy drug is widely used to treat various types of malignancies. Although the involvement of circadian clock in cisplatin metabolism and excretion has been reported, the effect of cisplatin on circadian rhythm remains unclear. In the present study, we investigated the effects of cisplatin on clock genes expression in mouse peripheral tissues. Cisplatin induced severe nephrotoxicity, as revealed by the significant increase of blood urea nitrogen and serum creatinine levels...
May 10, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29750764/linezolid-containing-treatment-regimens-for-tuberculosis-in-children
#8
Luis M Prieto, Begoña Santiago, Teresa Del Rosal, Begoña Carazo, Ana B Jiménez, Beatriz Pérez-Gorricho, Felipe Rubio, Alfredo Tagarro, Daniel Blázquez, David Moreno-Pérez, María J Mellado, Fernando Baquero-Artigao
BACKGROUND: In recent years there is an increasing interest in the use of linezolid for the treatment of tuberculosis (TB). METHODS: Patients under 18 years of age who received linezolid within the Spanish Pediatric TB Network (pTBred) from 2001 to 2016 were retrospectively included. Treatment characteristics, adverse events (AEs) and outcomes were analyzed. RESULTS: Fifteen children were included (53% male) with a median age of 3.6 years (IQR: 1...
May 10, 2018: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/29748197/minimally-invasive-delivery-of-hydrogel-encapsulated-amiodarone-to-the-epicardium-reduces-atrial-fibrillation
#9
Jose R Garcia, Peter F Campbell, Gautam Kumar, Jonathan J Langberg, Liliana Cesar, Juline N Deppen, Eric Y Shin, Neal K Bhatia, Lanfang Wang, Kai Xu, Frank Schneider, Brian Robinson, Andrés J García, Rebecca D Levit
BACKGROUND: Atrial fibrillation (AF) is the most common cardiac arrhythmia. Although treatment options for AF exist, many patients cannot be maintained in normal sinus rhythm. Amiodarone is an effective medication for AF but has limited clinical utility because of off-target tissue toxicity. METHODS: Here, we use a pig model of AF to test the efficacy of an amiodarone-containing polyethylene glycol-based hydrogel. The gel is placed directly on the atrial epicardium through the pericardial space in a minimally invasive procedure using a specially designed catheter...
May 2018: Circulation. Arrhythmia and Electrophysiology
https://www.readbyqxmd.com/read/29745273/metabolic-fate-and-subchronic-biological-effects-of-core-shell-structured-fe-3-o-4-sio-2-nh-2-nanoparticles
#10
Yueli Chen, Jinquan Li, Zhongxue Yuan, Jianghua Feng, Zhong Chen
Core-shell structured Fe3 O4 @SiO2 -NH2 nanoparticles (Fe@Si-NPs) demonstrated outstanding potentials in drug targeting and delivery and medical imaging. However, they have limited clinical applications due to unknown chronic bio-effects and potential bio-related risks. In this study, the subchronic biological effects and metabolic fate of 20 nm Fe@Si-NPs in Sprague-Dawley rats in 12 weeks were investigated by the biochemical assay and NMR-based metabonomic analysis using an intravenous model. Biofluids (plasma and urine) analysis provided the transportation, absorption, and excretion information of Fe@Si-NPs...
May 10, 2018: Nanotoxicology
https://www.readbyqxmd.com/read/29743445/increased-susceptibility-to-troglitazone-induced-mitochondrial-permeability-transition-in-type-2-diabetes-mellitus-model-rat
#11
Masahiro Segawa, Shuichi Sekine, Tomoyuki Sato, Kousei Ito
Troglitazone, a member of the thiazolidinedione class of antidiabetic drugs, was withdrawn from the market because it causes severe liver injury. One of the mechanisms for this adverse effect is thought to be mitochondrial toxicity. To investigate the characteristics of troglitazone-induced liver toxicity in more depth, the toxicological effects of troglitazone on hepatocytes and liver mitochondria were investigated using a rat model of type 2 diabetes mellitus (T2DM). Troglitazone was found to increase mitochondrial permeability transition (MPT) in the liver mitochondria of diabetic rats to a greater extent than in control rats, whereas mitochondrial membrane potential and oxidative phosphorylation were not affected...
2018: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/29742069/a-simple-robust-method-of-synthesis-of-copper-silver-core-shell-nano-particle-evaluation-of-its-structural-and-chemical-properties-with-anticancer-potency
#12
Milon Banik, Mousumi Patra, Debanjan Dutta, Riya Mukherjee, Tarakdas Basu
A simple method of synthesis of stable bimetallic copper-silver nanoparticle (Cu@Ag NP) was developed by successive reduction of Cu(NO3)2 and AgNO3, using hydrazine hydrate as the reducing agent and gelatine and Poly-vinyl pyrrolidone (PVP) as the capping agents. The round-shaped particles were of core-shell structure with a core of Cu0 atoms surrounded by a shell of Ag0 atoms. The size and the mol. wt. of the NPs were (100 ± 10) nm and (820 ± 157) Kd respectively; the particles were crystalline in nature and 90% of the precursors Cu(NO3)2 and AgNO3 were converted to the NPs...
May 9, 2018: Nanotechnology
https://www.readbyqxmd.com/read/29741394/effective-combination-therapy-of-percutaneous-ethanol-injection-and-chemotherapy-based-on-injectable-low-molecular-weight-gels
#13
Guotao Li, Yan Liang, Changzhen Sun, Xinyu Peng, Na Hao, Miaochang Liu, Wenxia Gao, Huayue Wu, Bin He
Percutaneous ethanol injection (PEI) therapy was used in liver cancer treatment, however, the therapeutic ethanol in PEI easily flew away from injected solid tumours and hinder the treatment effect. In this paper, injectable supramolecular gels formed by self-assembly of low molecular weight gelators (LMWGs) based on glycylglycine modified phenylboronic acid were prepared to localize ethanol and load chemotherapeutic drug for in situ synergistic therapy. The mechanism, morphology and rheological property of supramolecular gels were characterized by NMR, UV, SEM, etc...
May 9, 2018: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/29735688/cisplatin-dna-adduct-repair-of-transcribed-genes-is-controlled-by-two-circadian-programs-in-mouse-tissues
#14
Yanyan Yang, Ogun Adebali, Gang Wu, Christopher P Selby, Yi-Ying Chiou, Naim Rashid, Jinchuan Hu, John B Hogenesch, Aziz Sancar
Cisplatin is a major cancer chemotherapeutic drug. It kills cancer cells by damaging their DNA, mainly in the form of Pt-d(GpG) diadducts. However, it also has serious side effects, including nephrotoxicity and hepatotoxicity that limit its usefulness. Chronotherapy is taking circadian time into account during therapy to improve the therapeutic index, by improving efficacy and/or limiting toxicity. To this end, we tested the impact of clock time on excision repair of cisplatin-induced DNA damage at single-nucleotide resolution across the genome in mouse kidney and liver...
May 7, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29731843/antitumor-effects-of-brucine-immuno-nanoparticles-on-hepatocellular-carcinoma-in-vivo
#15
Jianmin Qin, Lin Yang, Xia Sheng, Zhongqiu Sa, Tao Huang, Qi Li, Kepan Gao, Qinghua Chen, Jingwei Ma, Hebai Shen
In vitro and in vivo studies have demonstrated that brucine is able to inhibit the proliferation of liver cancer cells and growth of animal tumors, and may be a promising anticancer drug. However, high toxicity, poor water solubility, short half-life, narrow therapeutic window, and similar therapeutic and toxic doses limit its clinical application in the treatment of malignant tumors. In our previous study, brucine immuno-nanoparticles were successfully prepared and added to the culture medium of liver cancer SMMC-7721 cells, and the results indicated that the brucine immuno-nanoparticles were able to target the cell membrane of liver cancer SMMC-7721 cells and significantly inhibit the proliferation, adhesion, invasion and metastasis of SMMC-7721 cells...
May 2018: Oncology Letters
https://www.readbyqxmd.com/read/29729369/reference-intervals-for-putative-biomarkers-of-drug-induced-liver-injury-and-liver-regeneration-in-healthy-human-volunteers
#16
Ben Francis, Joanna I Clarke, Lauren E Walker, Nathalie Brillant, Andrea L Jorgensen, B Kevin Park, Munir Pirmohamed, Daniel J Antoine
BACKGROUND & AIMS: The potential of mechanistic biomarkers to improve the prediction of drug-induced liver injury (DILI) and hepatic regeneration is widely acknowledged. We sought to determine reference intervals for new biomarkers of DILI and regeneration as well as to characterize their natural variability and impact of diurnal variation. METHODS: Serum samples from 200 healthy volunteers were recruited as part of a cross sectional study; of these, 50 subjects had weekly serial sampling over 3 weeks, while 24 had intensive blood sampling over a 24h period...
May 2, 2018: Journal of Hepatology
https://www.readbyqxmd.com/read/29728035/-effect-of-ginseng-rare-ginsenoside-components-combined-with-paclitaxel-on-a549-lung-cancer
#17
Lei Yang, Zhen-Hai Zhang, Xiao-Bin Jia
Traditional Chinese medicine combined with anticancer drugs is a new direction of clinical cancer therapy in recent years. In this study, the optimal ratio of ginseng rare ginsenoside components and paclitaxel was optimized by MTT method, and the proliferative, apoptotic and anti-tumor effects of lung cancer A549 cells were investigated. It was found that the inhibitory effect on the proliferation of lung cancer A549 cells was the same as that on paclitaxel when the ratio of rare ginseng rare ginsenoside components to paclitaxel was 4∶6...
April 2018: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/29723689/development-and-validation-of-a-test-to-identify-drugs-that-cause-idiosyncratic-drug-induced-liver-injury
#18
Andreas Benesic, Isabelle Rotter, Diana Dragoi, Sabine Weber, Marie-Luise Buchholtz, Alexander L Gerbes
BACKGROUND & AIMS: Idiosyncratic drug-induced liver injury (iDILI) is one of the most challenging diagnoses in hepatology. It is frequently impossible to identify the agent that has caused iDILI in patients who take multiple medicines. We developed an in vitro method to identify drugs that cause liver injury in patients, based on drug toxicity to monocyte-derived hepatocyte-like (MH) cells from patient blood samples. We then collected data on patients who were re-exposed to drugs found to be toxic in the MH test to validate test performance...
April 30, 2018: Clinical Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29720828/hepatoprotective-evaluation-of-trapa-natans-against-drug-induced-hepatotoxicity-of-antitubercular-agents-in-rats
#19
Talib Hussain, Gehad M Subaiea, Hina Firdous
Background: Medicinal herbs are significantly effective against a variety of liver disorders and Trapa natans was traditionally used for the treatment of anti-inflammatory, pain disorder, and various types of hepatic ailment. Objective: The purpose of this study was to evaluate the hepatoprotective activity of T. natans fruit peel extract against antitubercular drugs (isoniazid + rifampicin [INH + RIF])-induced hepatotoxicity in rats. Materials and Methods: Liver toxicity was induced by INH + RIF at a dose level of 50 mg/kg each, intraperitoneally...
April 2018: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/29709908/effects-of-oridonin-on-hepatic-cytochrome-p450-expression-and-activities-in-pxr-humanized-mice
#20
Zhang Yi-Wen, Bao Mei-Hua, Lou Xiao-Ya, Cheng Yu, Yu Jing, Zhou Hong-Hao
Oridonin, the major terpene found in Rabdosia rubescens, is widely used as dietary supplement or therapeutic drug, while the effects of oridonin on CYP450 were still unclear. The pregnane X receptor (PXR) is an important regulatory factor for major drug metabolism enzyme CYPs, and it has been reported to have species-specific differences. Therefore, this study has employed more reliable models PXR-humanized mouse to investigate the influence of oridonin on PXR and downstream metabolism enzyme. Eight-week-old male PXR-humanized mice were treated with oridonin by orally (0, 25, 50, 100, 200 mg/kg) for 15 d...
2018: Biological & Pharmaceutical Bulletin
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