当前位置： SCI文献检索 > TOXICOLOGY LETTERS期刊下所有文献 > A novel cell-based assay for the evaluation of immune- and inflammatory-related gene expression as biomarkers for the risk assessment of drug-induced liver injury.

A novel cell-based assay for the evaluation of immune- and inflammatory-related gene expression as biomarkers for the risk assessment of drug-induced liver injury.

Abstract：

:Drug-induced liver injury (DILI) is a major problem in drug development. Although some in vitro methods assessing DILI risk that utilize hepatic cell death or cellular stress as markers have been developed, the predictive ability of these tests is low. In this study, we sought to develop a novel cell-based assay for the risk assessment of DILI that considers drug metabolism as well as immune- and inflammatory-related gene expression. To accomplish this goal, human hepatoma HepaRG or HepG2 cells were treated with 96 drugs with different clinical DILI risks. The conditioned media were subsequently used to treat human promyelocytic leukemia HL-60 cells, and the mRNA expression levels of immune- and inflammatory-related genes in the cells were measured. An area under the receiver operating characteristic curve (ROC-AUC) was calculated to evaluate the predictive performance of the mRNA levels as markers to discriminate DILI risk. The expression of interleukin-8 (IL-8) in HL-60 cells treated with conditioned media from HepaRG cells (HL-60/HepaRG) exhibited the highest ROC-AUC value of 0.758, followed by the expression of IL-1β in HL-60/HepaRG (ROC-AUC: 0.726). Notably, the ROC-AUC values of these genes were higher in HL-60/HepaRG than in HL-60/HepG2, which suggests that HL-60/HepaRG has a higher potential for detecting the metabolic activation of drugs. An integrated score calculated from the levels of S100 calcium-binding protein A9 (S100A9), IL-1β, and IL-8 more precisely determined the DILI risks than individual gene expression did. The developed cell-based assay that utilizes immune-related gene expression would aid in the assessment of potential DILI risks.

journal_name

Toxicol Lett

journal_title

Toxicology letters

authors

Oda S,Matsuo K,Nakajima A,Yokoi T

doi

10.1016/j.toxlet.2015.10.029

subject

Has Abstract

pub_date

2016-01-22 00:00:00

pages

60-70

eissn

0378-4274

issn

1879-3169

pii

S0378-4274(15)30094-1

journal_volume

241

pub_type

杂志文章

相关文献

TOXICOLOGY LETTERS文献大全
  • Dibenzofuran induces oxidative stress, disruption of trans-mitochondrial membrane potential (ΔΨm) and G1 arrest in human hepatoma cell line.

    abstract：:Dioxins are a class of extremely toxic environmentally persistent pollutant, comprised of halogenated dibenzo-p-dioxins, dibenzofurans and biphenyls. Despite significant human exposure via multiple routes, very little is known about toxicity induced by dibenzofuran (DF). Current study shed lights on the potential toxi...

    journal_title：Toxicology letters

    pub_type： 杂志文章

    doi：10.1016/j.toxlet.2012.08.014

    authors： Jaiswal PK,Srivastava S,Gupta J,Thakur IS

    更新日期：2012-10-17 00:00:00

  • Pyrroloquinoline quinone-conferred neuroprotection in rotenone models of Parkinson's disease.

    abstract：:Pyrroloquinoline quinone (PQQ), a redox cofactor in the mitochondrial respiratory chain, has proven to protect neurons against glutamate-induced damage both in vitro and in vivo. This study was aimed to investigate the possible neuroprotective effects of PQQ in rotenone-induced Parkinson's disease (PD) model. Pre-trea...

    journal_title：Toxicology letters

    pub_type： 杂志文章

    doi：10.1016/j.toxlet.2015.08.011

    authors： Qin J,Wu M,Yu S,Gao X,Zhang J,Dong X,Ji J,Zhang Y,Zhou L,Zhang Q,Ding F

    更新日期：2015-11-04 00:00:00

  • Oleic acid increases intestinal absorption of the BCRP/ABCG2 substrate, mitoxantrone, in mice.

    abstract：:The efflux transporter breast cancer resistance protein (BCRP/ABCG2) decrease intestinal absorption of many food toxicants. Oleic acid increases absorption of the specific BCRP substrate mitoxantrone (MXR), and also BCRP gene expression in human intestinal Caco-2 cells, suggesting that oleic acid affect the BCRP funct...

    journal_title：Toxicology letters

    pub_type： 杂志文章

    doi：10.1016/j.toxlet.2015.06.009

    authors： Aspenström-Fagerlund B,Tallkvist J,Ilbäck NG,Glynn AW

    更新日期：2015-09-02 00:00:00

  • Comparison of urinary bromide levels among people in East Asia, and the effects of dietary intakes of cereals and marine products.

    abstract：:Groups of people with no occupational exposure to Br-containing chemicals (29-54 year old, mostly women) in Japan, China and Korea, respectively, offered spot urine samples. Those in China and Korea offered 24 h duplicates of foods of the day. Urine samples were analyzed for Br by ECD-gas chromatography (ECD-GC) after...

    journal_title：Toxicology letters

    pub_type： 杂志文章

    doi：10.1016/s0378-4274(02)00192-3

    authors： Kawai T,Zhang ZW,Moon CS,Shimbo S,Watanabe T,Matsuda-Inoguchi N,Higashikawa K,Ikeda M

    更新日期：2002-08-05 00:00:00

  • A keratin 18 transgenic zebrafish Tg(k18(2.9):RFP) treated with inorganic arsenite reveals visible overproliferation of epithelial cells.

    abstract：:Inorganic arsenic has strong human carcinogenic potential, but the availability of an animal model to study toxicity is extremely limited. Here, we used the transgenic zebrafish line Tg(k18(2.9):RFP) as an animal model to study arsenite toxicity. This line was chosen because the red fluorescent protein (RFP) is expres...

    journal_title：Toxicology letters

    pub_type： 杂志文章

    doi：10.1016/j.toxlet.2005.10.024

    authors： Wang YH,Chen YH,Wu TN,Lin YJ,Tsai HJ

    更新日期：2006-06-01 00:00:00

  • Aloe emodin induces hepatotoxicity by activating NF-κB inflammatory pathway and P53 apoptosis pathway in zebrafish.

    abstract：:The aim of this study was to investigate the hepatotoxic effect and its underlying mechanism of aloe emodin (AE). AE was docked with the targets of NF-κB inflammatory pathway and P53 apoptosis pathway respectively by using molecular docking technique. To verify the results of molecular docking and further investigate ...

    journal_title：Toxicology letters

    pub_type： 杂志文章

    doi：10.1016/j.toxlet.2019.02.007

    authors： Quan Y,Gong L,He J,Zhou Y,Liu M,Cao Z,Li Y,Peng C

    更新日期：2019-05-15 00:00:00

  • Effect of sulfur dioxide inhalation on CYP1A1 and CYP1A2 in rat liver and lung.

    abstract：:Sulfur dioxide (SO2) is a ubiquitous air pollutant, presents in low concentrations in the urban air, and in higher concentrations in the working environment. In the present study, male Wistar rats were housed in exposure chambers and treated with 14.00+/-1.53, 28.00+/-2.12 and 56.00+/-4.28 mg/m3 SO2 for 6 h/day for 7 ...

    journal_title：Toxicology letters

    pub_type： 杂志文章,随机对照试验

    doi：10.1016/j.toxlet.2005.06.002

    authors： Qin G,Meng Z

    更新日期：2005-12-30 00:00:00

  • Determination of arsenic in urine by atomic absorption spectrophotometry for biological monitoring of occupational exposure to arsenic.

    abstract：:An atomic absorption spectrophotometric (AAS) method was successfully applied to analysis of urine for arsenic (As) as a measure of biological monitoring of occupational exposure to As in Vietnam. The application of the method to urine samples from 75 non-exposed control urbanites (after 2-day abstinence from sea food...

    journal_title：Toxicology letters

    pub_type： 杂志文章

    doi：10.1016/s0378-4274(99)00087-9

    authors： Dang TM,Tran QT,Vu KV

    更新日期：1999-09-05 00:00:00

  • Autophagy mediates bronchial cell malignant transformation induced by chronic arsenic exposure via MEK/ERK1/2 pathway.

    abstract：:Chronic exposure to arsenic increases the risk of developing a variety of human cancers including lung carcinomas. However, the exact molecular mechanism underlying arsenic carcinogenicity remains largely unknown. Autophagy is a conserved catabolic process for maintaining cellular protein homeostasis whose defects mig...

    journal_title：Toxicology letters

    pub_type： 杂志文章

    doi：10.1016/j.toxlet.2020.06.006

    authors： Wu L,Wang Z,Li X,He X,Han Y,Chen Y,Liu L,Fu L,Zhang T

    更新日期：2020-10-10 00:00:00

  • An in vitro cytotoxicities comparison of 16 priority polycyclic aromatic hydrocarbons in human pulmonary alveolar epithelial cells HPAEpiC.

    abstract：:In present study, we compared for the first time the cytotoxicities of the 16 priority polycyclic aromatic hydrocarbons (PAHs) in human pulmonary alveolar epithelial cells HPAEpiC. Moreover, we examined the effects of each PAH on oxidative stress (SOD, GSH, and ROS), cell viability, extracellular LDH, and apoptosis. T...

    journal_title：Toxicology letters

    pub_type： 杂志文章

    doi：10.1016/j.toxlet.2018.03.005

    authors： Ke S,Liu Q,Yao Y,Zhang X,Sui G

    更新日期：2018-06-15 00:00:00

  • Ethylglucuronide in the urine as a marker of alcohol consumption during pregnancy: Comparison with four alcohol screening questionnaires.

    abstract：:Ethyl glucuronide (EtG) is an ethanol metabolite and EtG is used as a biomarker of alcohol drinking. EtG can be detected in the blood and in several biological matrices including urine, hair and nails. Alcohol consumption during pregnancy is a strong risk factor for fetus health so in the recent years different strate...

    journal_title：Toxicology letters

    pub_type： 杂志文章

    doi：10.1016/j.toxlet.2017.04.016

    authors： Ferraguti G,Ciolli P,Carito V,Battagliese G,Mancinelli R,Ciafrè S,Tirassa P,Ciccarelli R,Cipriani A,Messina MP,Fiore M,Ceccanti M

    更新日期：2017-06-05 00:00:00

  • Research chemicals marketed as legal highs: the case of pipradrol derivatives.

    abstract：:Between 1997 and 2011, more than 200 new substances were notified through the early-warning system, with the record number of 49 novel molecules reported in 2011. The pattern of acute toxicity associated with the consumption of these new substances is generally similar to that seen with traditional drugs of abuse. Rec...

    journal_title：Toxicology letters

    pub_type： 杂志文章,评审

    doi：10.1016/j.toxlet.2012.04.019

    authors： Coppola M,Mondola R

    更新日期：2012-07-07 00:00:00

  • Developmental exposure to cuprizone reduces intermediate-stage progenitor cells and cholinergic signals in the hippocampal neurogenesis in rat offspring.

    abstract：:The exposure to cuprizone (CPZ) leads to demyelination in the central nervous system in rodents. To examine the developmental effects of CPZ exposure on hippocampal neurogenesis, pregnant rats were treated with 0, 0.1 or 0.4% CPZ in the diet from gestational day 6 to day 21 after delivery. On postnatal day 21, male of...

    journal_title：Toxicology letters

    pub_type： 杂志文章

    doi：10.1016/j.toxlet.2015.01.022

    authors： Abe H,Tanaka T,Kimura M,Mizukami S,Imatanaka N,Akahori Y,Yoshida T,Shibutani M

    更新日期：2015-05-05 00:00:00

  • Genotoxicity--threshold or not? Introduction of cases of industrial chemicals.

    abstract：:Many industrially and environmentally important industrial carcinogens display effects that lead them to be viewed and regulated as 'genotoxic compounds'. Some of these chemicals cause experimental tumours only at high or toxic doses. The current view is that non-threshold principles should be applied for risk assessm...

    journal_title：Toxicology letters

    pub_type： 杂志文章,评审

    doi：10.1016/s0378-4274(02)00495-2

    authors： Bolt HM

    更新日期：2003-04-11 00:00:00

  • DBP-induced endoplasmic reticulum stress in male germ cells causes autophagy, which has a cytoprotective role against apoptosis in vitro and in vivo.

    abstract：:Recently, spermatogenic cell apoptosis was shown to play a key role in the induction of testicular atrophy by dibutyl phthalate (DBP), thus causing reproductive toxicology. However, the molecular events induced by DBP in apoptotic germ cells remain unclear. In the present study, the mouse spermatocyte-derived GC-2 cel...

    journal_title：Toxicology letters

    pub_type： 杂志文章

    doi：10.1016/j.toxlet.2016.01.016

    authors： Zhang G,Liu K,Ling X,Wang Z,Zou P,Wang X,Gao J,Yin L,Zhang X,Liu J,Ao L,Cao J

    更新日期：2016-03-14 00:00:00

  • General 4-week toxicity study with EMS in the rat.

    abstract：:In this subacute toxicity study, ethyl methanesulfonate (EMS) was administered daily by oral gavage to SPF-bred Wistar rats of both sexes at dose levels of 20, 60 and 180/120 mg/kg body weight (bw)/day for a period of 28 days (for 19 days in the high-dose group). A control group was treated similarly with the vehicle,...

    journal_title：Toxicology letters

    pub_type： 杂志文章

    doi：10.1016/j.toxlet.2009.04.031

    authors： Pfister T,Eichinger-Chapelon A

    更新日期：2009-11-12 00:00:00

  • Effect of chronic herbicide intoxication on in vivo activities of certain enzymes in the liver of freshwater fish Nemachelius denisonii (day).

    abstract：:Effect of 120 days of continuous exposure of three sublethal concentrations (1/2, 1/4 and 1/8 fractions of 96 h LC50) of Basalin on alkaline phosphatase (Alk P), acid phosphatase (Acid P), lactic dehydrogenase (LDH), succinic dehydrogenase (SDH), glutamic oxaloacetic transaminase (GOT), and glutamic pyruvic transamina...

    journal_title：Toxicology letters

    pub_type： 杂志文章

    doi：10.1016/0378-4274(83)90184-4

    authors： Rashatwar SS,Ilyas R

    更新日期：1983-05-01 00:00:00

  • Influence of anesthetics on endogenous and recombinantly expressed G protein-coupled receptors in the Xenopus oocyte.

    abstract：:1. The oocyte of the African clawed toad (Xenopus laevis) offers a reliable, sensitive and disease resistant system to investigate recombinantly and endogenously expressed Ca2+ signaling G protein-coupled receptors and their intracellular signaling pathways. 2. To study receptor induced Ca2+ release, two-electrode vol...

    journal_title：Toxicology letters

    pub_type： 杂志文章,评审

    doi：10.1016/s0378-4274(98)00201-x

    authors： Nietgen GW,Hönemann CW,Durieux ME

    更新日期：1998-11-23 00:00:00

  • Ten-day repeated-exposure inhalation study of dimethylformamide (DMF) in cynomolgus monkeys.

    abstract：:Cynomolgus monkeys showed no measurable adverse effects following inhalation of 500 ppm dimethylformamide (DMF), 6 h/d, 5 d/wk, for 2 weeks either when exposed whole-body or head-only (one monkey per exposure route). Measurement of DMF concentrations into and out of the head-only exposure unit along with measurement o...

    journal_title：Toxicology letters

    pub_type： 杂志文章

    doi：10.1016/0378-4274(91)90076-i

    authors： Hurtt ME,McCooey KT,Placke ME,Kennedy GL

    更新日期：1991-12-01 00:00:00

  • Hexavalent chromium and ascorbic acid interaction on proliferation of the human cell line NHIK3025.

    abstract：:When cells from the human cell line NHIK3025 were cultured for 4 days, with hexavalent chromium (K2Cr2O7) at a concentration of 8 . 10(-7)M, the relative cell number was reduced to 38%. This effect of hexavalent chromium was abolished if ascorbic acid and chromate were added simultaneously to the incubation medium, bu...

    journal_title：Toxicology letters

    pub_type： 杂志文章

    doi：10.1016/0378-4274(82)90146-1

    authors： Jakobsen K,Eik-Nes KB

    更新日期：1982-09-01 00:00:00

  • Mitochondrial DNA hypomethylation in chrome plating workers.

    abstract：:A matched case-control study was conducted to examine the relationship between chromium (Cr) exposure and variation in mitochondrial (mt) DNA methylation. We enrolled 29 pairs of subjects in this study; Cr exposure was confirmed in the cases by detecting blood Cr and other metal ion concentrations. DNA damage caused b...

    journal_title：Toxicology letters

    pub_type： 杂志文章

    doi：10.1016/j.toxlet.2015.11.031

    authors： Yang L,Xia B,Yang X,Ding H,Wu D,Zhang H,Jiang G,Liu J,Zhuang Z

    更新日期：2016-01-22 00:00:00

  • The contribution of dermal exposure to the internal exposure of bisphenol A in man.

    abstract：:New findings on Bisphenol A (BPA) contents in thermal printing papers, and receipts, in g/kg concentrations and on its dermal uptake (up to 60%) prompted us to assess the risk arising from dermal exposure. Using physiologically based toxicokinetic modelling, we simulated concentrations in blood, in liver and kidney, t...

    journal_title：Toxicology letters

    pub_type： 杂志文章

    doi：10.1016/j.toxlet.2011.04.032

    authors： Mielke H,Partosch F,Gundert-Remy U

    更新日期：2011-07-28 00:00:00

  • Dimethocaine, a synthetic cocaine derivative: studies on its in vitro metabolism catalyzed by P450s and NAT2.

    abstract：:Dimethocaine (DMC), a synthetic derivative of cocaine, is distributed and consumed as "new psychoactive substance" (NPS) without any safety testing at the forefront. It is mainly metabolized by N-acetylation, N-deethylation or hydroxylation. Therefore, the aim of the presented study was to determine the human NAT and ...

    journal_title：Toxicology letters

    pub_type： 杂志文章

    doi：10.1016/j.toxlet.2013.11.033

    authors： Meyer MR,Lindauer C,Maurer HH

    更新日期：2014-02-10 00:00:00

  • Binding interactions of halogenated bisphenol A with mouse PPARα: In vitro investigation and molecular dynamics simulation.

    abstract：:The binding of bisphenol A (BPA) and its halogenated derivatives (halogenated BPAs) to mouse peroxisome proliferator-activated receptor α ligand binding domain (mPPARα-LBD) was examined by a combination of in vitro investigation and in silico simulation. Fluorescence polarization (FP) assay showed that halogenated BPA...

    journal_title：Toxicology letters

    pub_type： 杂志文章

    doi：10.1016/j.toxlet.2017.11.004

    authors： Zhang J,Li T,Wang T,Guan T,Yu H,Li Z,Wang Y,Wang Y,Zhang T

    更新日期：2018-02-01 00:00:00

  • The distribution of esterases in the skin of the minipig.

    abstract：:Skin esterases serve an important pharmacological function as they can be utilised for activation of topically applied ester prodrugs. Understanding the nature of these enzymes, with respect to their role and local activity, is essential to defining the efficacy of ester prodrugs. Minipigs are used as models to study ...

    journal_title：Toxicology letters

    pub_type： 杂志文章

    doi：10.1016/j.toxlet.2007.07.004

    authors： Jewell C,Prusakiewicz JJ,Ackermann C,Payne NA,Fate G,Williams FM

    更新日期：2007-09-10 00:00:00

  • Development and characterization of a rat model of chronic obstructive pulmonary disease (COPD) induced by sidestream cigarette smoke.

    abstract：:Cigarette smoke (CS) induced chronic obstructive pulmonary disease (COPD) has been emerging as a great health problem in China. However, lack of appropriate animal model slows down the progress in understanding pathogenesis of the disease. The aim of current study is to establish and evaluate a more adequate rat model...

    journal_title：Toxicology letters

    pub_type： 杂志文章

    doi：10.1016/j.toxlet.2009.06.850

    authors： Zheng H,Liu Y,Huang T,Fang Z,Li G,He S

    更新日期：2009-09-28 00:00:00

  • Antagonistic effect of melatonin against cyanide-induced seizures and acute lethality in mice.

    abstract：:The effect of melatonin on potassium cyanide-induced neurotoxicity was investigated in vivo. The ED50 value of potassium cyanide, as measured by induction of tonic and clonic seizures, was significantly increased by 1.5- or 1.8-fold by s.c. preinjection of melatonin (20, 100 or 345 mg/kg) in mice. The preventive effec...

    journal_title：Toxicology letters

    pub_type： 杂志文章

    doi：10.1016/0378-4274(96)03671-5

    authors： Yamamoto H,Tang HW

    更新日期：1996-09-01 00:00:00

  • Fate of the teratogenic and carcinogenic ochratoxin A in human perfused placenta.

    abstract：:Ochratoxin A (OTA) is one of the most frequent mycotoxins detected in human blood worldwide. Apart from its well known nephrotoxicity, OTA-induced teratogenicity and carcinogenicity proven in animals are potential effects also in humans. Pregnant women have been exposed to this food contaminant via dietary exposure in...

    journal_title：Toxicology letters

    pub_type： 杂志文章

    doi：10.1016/j.toxlet.2011.10.013

    authors： Woo CS,Partanen H,Myllynen P,Vähäkangas K,El-Nezami H

    更新日期：2012-01-05 00:00:00

  • Expression of macrophage migration inhibitory factor by osteoblastic cells: protection against cadmium toxicity.

    abstract：:Exposition to cadmium (Cd) has been linked to bone metabolism alterations and occurrence of osteoporosis. Despite its known renal toxicity which indirectly disrupts bone metabolism through impairment of vitamin D synthesis, increasing evidence argues for the direct action of Cd on bone-forming osteoblasts. Indeed, acc...

    journal_title：Toxicology letters

    pub_type： 杂志文章

    doi：10.1016/j.toxlet.2012.10.006

    authors： Lizotte J,Abed E,Signor C,Malu DT,Cuevas J,Kevorkova O,Sanchez-Dardon J,Satoskar A,Scorza T,Jumarie C,Moreau R

    更新日期：2012-12-17 00:00:00

  • Setting legislative norms for environmental lead exposure: results of an epidemiological survey in the east of Belgium.

    abstract：:Blood lead concentrations (Pb-B, microgram/100 ml) was measured in children and adults, both sexes, living in and around Liège (control group, n = 859) and in the urban center of Verviers (exposed group, n = 568) where houses with lead piping are supplied with corrosive drinking water. In control children, the mean Pb...

    journal_title：Toxicology letters

    pub_type： 杂志文章

    doi：10.1016/0378-4274(81)90077-1

    authors： Sartor FA,Rondia D

    更新日期：1981-01-01 00:00:00