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drug induced liver toxicity

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https://www.readbyqxmd.com/read/28440434/preclinical-studies-for-the-combination-of-paclitaxel-and-curcumin-in-cancer-therapy-review
#1
Yumeng Wei, Xinlin Pu, Ling Zhao
Cancer is one of the most common causes of death and remains the first in China and the second in the US. The common treatments for cancer include surgery, radiation, chemotherapy, targeted therapy and immunotherapy, while chemotherapy remains one of the most important treatments. However, the efficacy of chemotherapy is limited due to drug induced-toxicities and resistance, particularly multiple drug resistance (MDR). Therefore, discovery and development of novel therapeutic drugs and/or combination therapy are urgently needed to reduce toxicity and improve efficacy...
April 20, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28438569/methylprednisolone-liver-toxicity-a-new-case-and-a-french-regional-pharmacovigilance-survey
#2
Jérôme Dumortier, Judith Cottin, Caroline Lavie, Olivier Guillaud, Valérie Hervieu, Christine Chambon-Augoyard, Jean-Yves Scoazec, Sandra Vukusic, Thierry Vial
Reported hepatotoxicity induced by corticosteroids is very rare, and the diagnosis is highly challenging in the context of auto-immune disease. We report here a case of high-dose methylprednisolone (MP)-induced acute hepatitis confirmed by liver histology in a patient with multiple sclerosis (MS) and a case series (n=4) notified to the French Pharmacovigilance center of Lyon. In all 5 cases, other common causes of hepatitis were excluded. The causal relationship with MP pulse therapy was supported by the fact that MP was the only culprit drug...
April 21, 2017: Clinics and Research in Hepatology and Gastroenterology
https://www.readbyqxmd.com/read/28437625/imaging-guided-synergetic-therapy-of-orthotopic-transplantation-tumor-by-superselectively-arterial-administration-of-microwave-induced-microcapsules
#3
Shunsong Tang, Changhui Fu, Longfei Tan, Tianlong Liu, Jingsong Mao, Xiangling Ren, Hongying Su, Dan Long, Qianqian Chai, Zhongbing Huang, Xudong Chen, Jingzhuo Wang, Jun Ren, Xianwei Meng
It is an ambitious target to improve overall Hepatocellular Carcinoma therapeutic effects. Recently, MW ablation has emerged as a powerful thermal ablation technique, affording favorable survival with excellent local tumor control. To achieve better therapeutic effects of MW ablation, MW sensitizers are prepared for enhanced MW ablation to preferentially heat tumor territory. However, it is still not practicable for treatment of the orthotopic transplantation tumor. Herein, biocompatible and degradable methoxy poly(ethylene glycol)-poly(lactic-co-glycolic acid) (mPEG-PLGA) microcapsules with hierarchical structure have been designed for microwave-induced tumor therapy...
April 14, 2017: Biomaterials
https://www.readbyqxmd.com/read/28436314/metabolomic-approaches-in-the-discovery-of-potential-urinary-biomarkers-of-drug-induced-liver-injury-dili
#4
Ana Margarida Araújo, Márcia Carvalho, Félix Carvalho, Maria de Lourdes Bastos, Paula Guedes de Pinho
Drug-induced liver injury (DILI) is a major safety issue during drug development, as well as the most common cause for the withdrawal of drugs from the pharmaceutical market. The identification of DILI biomarkers is a labor-intensive area. Conventional biomarkers are not specific and often only appear at significant levels when liver damage is substantial. Therefore, new biomarkers for early identification of hepatotoxicity during the drug discovery process are needed, thus resulting in lower development costs and safer drugs...
April 24, 2017: Critical Reviews in Toxicology
https://www.readbyqxmd.com/read/28433708/toxicological-characterisation-of-two-novel-selective-aryl-hydrocarbon-receptor-modulators-in-sprague-dawley-rats
#5
Selma Mahiout, Jere Lindén, Javier Esteban, Ismael Sánchez-Pérez, Satu Sankari, Lars Pettersson, Helen Håkansson, Raimo Pohjanvirta
The aryl hydrocarbon receptor (AHR) mediates the toxicity of dioxins, but also plays important physiological roles. Selective AHR modulators, which elicit some effects imparted by this receptor without causing the marked toxicity of dioxins, are presently under intense scrutiny. Two novel such compounds are IMA-08401 (N-acetyl-N-phenyl-4-acetoxy-5-chloro-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide) and IMA-07101 (N-acetyl-N-(4-trifluoromethylphenyl)-4-acetoxy-1,2-dihydro-5-methoxy-1-methyl-2-oxo-quinoline-3-carboxamide)...
April 19, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28425350/metabolomics-approach-discriminates-toxicity-index-of-pyrazinamide-and-its-metabolic-products-pyrazinoic-acid-and-5-hydroxy-pyrazinoic-acid
#6
A Rawat, S Chaturvedi, A K Singh, A Guleria, D Dubey, A K Keshari, V Raj, A Rai, A Prakash, U Kumar, D Kumar, S Saha
Pyrazinamide (PYZ)-an essential component of primary drug regimen used for the treatment and management of multidrug resistant or latent tuberculosis-is well known for its hepatoxicity. However, the mechanism of PYZ-induced hepatotoxicity is still unknown to researchers. Studies have shown that the drug is metabolized in the liver to pyrazinoic acid (PA) and 5-hydroxy pyrazinoic acid (5-OHPA) which individually may cause different degrees of hepatotoxicity. To evaluate this hypothesis, PYZ, PA, and 5-OHPA were administered to albino Wistar rats orally (respectively, at 250, 125, and 125 mg kg(-1) for 28 days)...
January 1, 2017: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/28423950/hepatoprotective-and-free-radical-scavenging-actions-of-quercetin-nanoparticles-on-a%C3%AF-atoxin-b1-induced-liver-damage-in-vitro-in-vivo-studies
#7
Aziz Eftekhari, Elham Ahmadian, Vahid Panahi-Azar, Hedayat Hosseini, Mahnaz Tabibiazar, Solmaz Maleki Dizaj
The objective of present study was in vitro and in vivo evaluation of hepatoprotective and antioxidant activity of Quercetin nanoparticles (Q NPs) against toxicity induced by aflatoxin B1. The Q NPs were prepared using precipitation method. Hepatocytes were prepared by the method of collagenase enzyme perfusion via portal vein. The NPs were characterized in terms of size and morphology using dynamic light scattering (DLS) and transmission electron microscopy (TEM), respectively. The level of parameters, such as cell death, ROS formation, lipid peroxidation, mitochondrial membrane potential and cellular glutathione (GSH) content, in the aflatoxin B1-treated and non-treated hepatocytes were determined and the mentioned markers were assessed in the presence of Q NPs...
April 20, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/28417920/evaluation-of-the-potential-risk-of-drugs-to-induce-hepatotoxicity-in-human-relationships-between-hepatic-steatosis-observed-in-non-clinical-toxicity-study-and-hepatotoxicity-in-humans
#8
Keisuke Goda, Akio Kobayashi, Akemi Takahashi, Tadakazu Takahashi, Kosuke Saito, Keiko Maekawa, Yoshiro Saito, Shoichiro Sugai
In the development of drugs, we sometimes encounter fatty change of the hepatocytes (steatosis) which is not accompanied by degenerative change in the liver in non-clinical toxicity studies. In this study, we investigated the relationships between fatty change of the hepatocytes noted in non-clinical toxicity studies of compound X, a candidate compound in drug development, and mitochondrial dysfunction in order to estimate the potential risk of the compound to induce drug-induced liver injury (DILI) in humans...
April 12, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28416868/a-synergistic-effect-of-cremophor-and-beta-glucosylceramide-to-exert-liver-and-sugar-protection
#9
Yehudit Shabat, Yaron Ilan
Many commonly used drugs carry the potential to induce hepatotoxicity, and a large number of foods and beverages induce an increase in blood sugar levels. A change in lifestyle by omitting these compounds is not applicable in many circumstances. β-Glucosylceramide (GC) is a naturally occurring glycosphingolipid that exerts an effect on the immune system. Cremophor EL (CrEL) is a synthetic, nonionic surfactant that is used as a vehicle for the administration of water-insoluble compounds. The aim of the present study was to determine the synergistic effect of oral administration of the combination of GC and CrEL (GCC) when added to potential toxic substrates or to sugar-enriched compounds...
April 2017: Journal of Food Science and Technology
https://www.readbyqxmd.com/read/28412648/content-decline-of-serca-inhibitors-saikosaponin-a-and-d-attenuates-cardiotoxicity-and-hepatotoxicity-of-vinegar-baked-radix-bupleuri
#10
Shifeng Wang, Yuxin Zhang, Qiao Zhang, Sha Peng, Chen Shen, Yangyang Yu, Minyu Zhang, Wei Yang, Qinghua Wu, Yanling Zhang, Shiyou Li, Yanjiang Qiao
Improper usage of unprocessed Radix bupleuri root (chaihu) may cause cardiotoxicity and liver injury. Baking herb with vinegar is believed to attenuate the adverse responses. However, the chemical and molecular basis involved remained unclear. To this end, we investigated the in vitro toxicity of saikosaponin a, c, d, and their hydrolysates saikosaponin b1 and b2. Results showed that SSa and SSd possessed higher affinity with sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA) by molecular docking, and exhibited stronger toxic responses on cardiomyocytes and hepatocytes than the other three saikosaponins in equivalent concentrations...
April 4, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/28391356/rat-precision-cut-liver-slices-predict-drug-induced-cholestatic-injury
#11
Viktoriia Starokozhko, Rick Greupink, Petra van de Broek, Nashwa Soliman, Samiksha Ghimire, Inge A M de Graaf, Geny M M Groothuis
Drug-induced cholestasis (DIC) is one of the leading manifestations of drug-induced liver injury (DILI). As the underlying mechanisms for DIC are not fully known and specific and predictive biomarkers and pre-clinical models are lacking, the occurrence of DIC is often only reported when the drug has been approved for registration. Therefore, appropriate models that predict the cholestatic potential of drug candidates and/or provide insight into the mechanism of DIC are highly needed. We investigated the application of rat precision-cut liver slices (PCLS) to predict DIC, using several biomarkers of cholestasis: hepatocyte viability, intracellular accumulation of total as well as individual bile acids and changes in the expression of genes known to play a role in cholestasis...
April 8, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28388498/raman-spectroscopy-for-the-detection-of-organ-distribution-and-clearance-of-pegylated-reduced-graphene-oxide-and-biological-consequences
#12
Santhakumar Syama, Willi Paul, Arumugam Sabareeswaran, Parayanthala Valappil Mohanan
Graphene, a 2D carbon material has found vast application in biomedical field because of its exciting physico-chemical properties. The large planar sheet like structure helps graphene to act as an effective carrier of drug or biomolecules in enormous amount. However, limited data available on the biocompatibility of graphene upon interaction with the biological system prompts us to evaluate their toxicity in animal model. In this study organ distribution, clearance and toxicity of PEGylated reduced nanographene (PrGO) on Swiss Albino mice was investigated after intraperitoneal and intravenous administration...
July 2017: Biomaterials
https://www.readbyqxmd.com/read/28388302/genome-wide-association-and-replication-study-of-hepatotoxicity-induced-by-antiretrovirals-alone-or-with-concomitant-anti-tuberculosis-drugs
#13
Zelalem Petros, Ming Ta Michael Lee, Atsushi Takahashi, Yanfei Zhang, Getnet Yimer, Abiy Habtewold, Ina Schuppe-Koistinen, Taisei Mushiroda, Eyasu Makonnen, Michiaki Kubo, Eleni Aklillu
Drug-induced hepatotoxicity (DIH) is a common adverse event that is associated with both antiretroviral (ARV) and anti-tuberculosis drugs (ATD). Moreover, the genetic variations predisposing ARV- and ARV-ATD-induced liver toxicity in African populations are not well investigated, despite the two diseases being the major global health problems in sub-Saharan Africa. We performed a genome-wide association study (GWAS) and replication study to identify the genetic variants linked to the risk of developing DIH due to ARV drugs alone, and ARV-ATD co-treatment in Ethiopian HIV-positive patients...
April 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/28386997/the-transformation-in-biomarker-detection-and-management-of-drug-induced-liver-injury
#14
REVIEW
Rachel J Church, Paul B Watkins
Drug-induced liver injury (DILI) is a major concern for patients, care givers and the pharmaceutical industry. Interpretation of the serum biomarkers routinely used to detect and monitor DILI, which have not changed in almost 50 years, can be improved with recently proposed models employing quantitative systems pharmacology. In addition, several newer serum biomarkers are showing great promise. Studies in rodents indicate that the ratio of the caspase cleaved fragment of cytokeratin 18 to total K18 in serum (termed the "apoptotic index") estimates the relative proportions of apoptosis vs necrosis during drug-induced liver injury...
April 7, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28383671/drug-induced-liver-injury-in-oncology
#15
A D Ricart
Liver regeneration has been an adaptation of vertebrates through evolutionary events to protect them from environmental pressures (e.g. ingested toxins). Elevated serum levels of aminotransferases generally indicate liver injury, but do not necessarily reflect or predict hepatotoxicity. Drug-induced liver injury (DILI) is first classified as predictable or unpredictable (idiosyncratic). Predictable DILI is dose-related and occurs shortly after exposure (e.g. high dose alkylating agents). Unpredictable reactions result from a succession of unlikely events, a "multihit" process (e...
April 5, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28382404/prediction-of-hepatotoxicity-for-drugs-using-human-pluripotent-stem-cell-derived-hepatocytes
#16
Jong Hyun Kim, Min Wang, Jaehun Lee, Han-Jin Park, Chungseong Han, Hee Su Hong, Jeong Seong Kim, Geun Ho An, Kijung Park, Hee-Kyung Park, Shi Feng Zhu, Xiao-Bo Sun, Jong-Hoon Kim, Dong-Hun Woo
Drug-induced liver toxicity is a main reason for withdrawals of new drugs in late clinical phases and post-launch of the drugs. Thus, hepatotoxicity screening of drug candidates in pre-clinical stage is important for reducing drug attrition rates during the clinical development process. Here, we show commercially available hepatocytes that could be used for early toxicity evaluation of drug candidates. From our hepatic differentiation technology, we obtained highly pure (≥98%) hepatocytes from human embryonic stem cells (hESCs) having mature phenotypes and similar gene expression profiles with those of primary human tissues...
April 5, 2017: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/28380448/glibenclamide-a-diabetic-drug-prevents-acute-radiationinduced-liver-injury-of-mice-via-up-regulating-intracellular-ros-and-subsequently-activating-akt-nf-%C3%AE%C2%BAb-pathway
#17
Hu Liu, Shichao Wang, Zhao Wu, Ziyun Huang, Wei You Chen, Yanyong Yang, Jianguo Cui, Cong Liu, Hainan Zhao, Jiaming Guo, Pei Zhang, Fu Gao, Bailong Li, Jianming Cai
BACKGROUND: Acute radiation-induced liver injury is a limitation for hepatoma radiotherapy. Come so far the clinical treatments are insufficient. The effective, specific, low toxicity and novel drugs are in powerful need. Glibenclamide is a common hypoglycemic. Some studies have revealed its relation with intracellular reactive oxygen species, the crucial mediator to radiation injury. This study is aimed to investigate if glibenclamide could act on the acute radiation-induced liver injury...
March 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28379594/pyrrolizidine-alkaloids-enhance-alcohol-induced-hepatocytotoxicity-in-vitro-in-normal-human-hepatocytes
#18
M G Neuman, L B Cohen, V Steenkamp
OBJECTIVE: Herbal remedies containing pyrrilidozine alkaloids (PA)s can induce liver damage, including hepato-sinusoidal obstruction syndrome (HSOS) or veno-occlusive liver disease (VOD). Some individuals misusing alcohol consume also teas and/or herbal remedies containing PA. The interaction or additive toxicity of alcohol to PA toxicity needs to be addressed. The objectives of this study are 1) to review the scientific literature on the PA-induced liver toxicity; 2) identify possible mechanism(s) involved in PA-induced hepatocytotoxicity in the presence or absence of ethanol (EtOH) in vitro in normal human hepatocytes (NHH) in primary culture...
March 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28379592/severe-hepatocytotoxicity-linked-to-denosumab
#19
S Malnick, Y Maor, E Melzer, N N Ziv-Sokolowskaia, M G Neuman
OBJECTIVE: Denosumab (Prolia, Amgen, Thousand Oaks, CA, USA) is a fully human antibody to the receptor activator of nuclear factor-KB ligand (RANKL). We present a case of submassive hepatic necrosis with evidence implicating cytokine induction resulting from an immune reaction to denosumab. CASE REPORT: A 72-year-old lady presented with elevated liver enzymes. One month previously, she received a s/c administration of 60 mg of denosumab. Viral hepatitis A, B and C and human herpes viruses 6-7 were negative as were routine autoimmune serology...
March 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28379587/drug-induced-liver-injury-2017-the-diagnosis-is-not-easy-but-always-to-keep-in-mind
#20
G Marrone, F G Vaccaro, M Biolato, L Miele, A Liguori, C Araneo, F R Ponziani, N Mores, A Gasbarrini, A Grieco
A drug-induced liver injury (DILI) is defined as a liver injury caused by exposure to a drug or a non-infectious toxic agent with a variable degree of organ dysfunction. A better understanding of DILI epidemiology has been obtained in recent years with the institution of international registries in the United States and Europe. Despite the advances in the understanding and characterization of the phenomenon, DILI remains an exclusion diagnosis so, probability scores and the analysis of literature reports are useful tools in dealing with a suspected DILI...
March 2017: European Review for Medical and Pharmacological Sciences
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