当前位置： SCI文献检索 > ARCHIVES OF TOXICOLOGY期刊下所有文献 > In vitro assessment of drug-induced liver steatosis based on human dermal stem cell-derived hepatic cells.

In vitro assessment of drug-induced liver steatosis based on human dermal stem cell-derived hepatic cells.

Abstract：

:Steatosis, also known as fatty liver disease (FLD), is a disorder in which the lipid metabolism of the liver is disturbed, leading to the abnormal retention of lipids in hepatocytes. FLD can be induced by several drugs, and although it is mostly asymptomatic, it can lead to steatohepatitis, which is associated with liver inflammation and damage. Drug-induced liver injury is currently the major cause of postmarketing withdrawal of pharmaceuticals and discontinuation of the development of new chemical entities. Therefore, the potential induction of steatosis must be evaluated during preclinical drug development. However, robust human-relevant in vitro models are lacking. In the present study, we explore the applicability of hepatic cells (hSKP-HPCs) derived from postnatal skin precursors, a stem cell population residing in human dermis, to investigate the steatosis-inducing effects of sodium valproate (Na-VPA). Exposure of hSKP-HPC to sub-cytotoxic concentrations of this reference steatogenic compound showed an increased intracellular accumulation of lipid droplets, and the modulation of key factors involved in lipid metabolism. Using a toxicogenomics approach, we further compared Na-VPA-treated hSKP-HPC and Na-VPA-treated primary human hepatocytes to liver samples from patients suffering from mild and advanced steatosis. Our data show that in hSKP-HPC exposed to Na-VPA and liver samples of patients suffering from mild steatosis, but not in primary human hepatocytes, "liver steatosis" was efficiently identified as a toxicological response. These findings illustrate the potential of hSKP-HPC as a human-relevant in vitro model to identify hepatosteatotic effects of chemical compounds.

journal_name

Arch Toxicol

journal_title

Archives of toxicology

authors

Rodrigues RM,Branson S,De Boe V,Sachinidis A,Rogiers V,De Kock J,Vanhaecke T

doi

10.1007/s00204-015-1483-z

subject

Has Abstract

pub_date

2016-03-01 00:00:00

pages

677-89

issue

3

eissn

0340-5761

issn

1432-0738

pii

10.1007/s00204-015-1483-z

journal_volume

90

pub_type

杂志文章

相关文献

ARCHIVES OF TOXICOLOGY文献大全
  • Mechanisms involved in the transport of mercuric ions in target tissues.

    abstract：:Mercury exists in the environment in various forms, all of which pose a risk to human health. Despite guidelines regulating the industrial release of mercury into the environment, humans continue to be exposed regularly to various forms of this metal via inhalation or ingestion. Following exposure, mercuric ions are t...

    journal_title：Archives of toxicology

    pub_type： 杂志文章,评审

    doi：10.1007/s00204-016-1803-y

    authors： Bridges CC,Zalups RK

    更新日期：2017-01-01 00:00:00

  • miR-138-1* regulates aflatoxin B1-induced malignant transformation of BEAS-2B cells by targeting PDK1.

    abstract：:Environmental carcinogens-induced lung cancer and potential mechanisms have attracted widespread attention. Currently, microRNAs (miRNAs) have been recognized as key players in development of cancer, among which guide strand of miRNA has been well documented rather than its passenger strand (miRNA*). Our previous stud...

    journal_title：Archives of toxicology

    pub_type： 杂志文章

    doi：10.1007/s00204-015-1551-4

    authors： Wang Y,Zhang Z,Wang H,Zhang Y,Ji M,Xu H,Wang C,Sun Z,Gao W,Wang SL

    更新日期：2016-05-01 00:00:00

  • Disposition, elimination, and metabolism of tri-o-cresyl phosphate following daily oral administration in Fischer 344 male rats.

    abstract：:The disposition, elimination, and metabolism of 50 mg/kg (1.36 muCi/animal) of tri-o-cresyl [phenyl-U-14C] phosphate after ten daily oral doses was investigated in adult male Fischer 344 rats. Groups of three treated animals were killed at intervals of 24, 48, 72, and 96 h after the last administrations. Generally, th...

    journal_title：Archives of toxicology

    pub_type： 杂志文章

    doi：10.1007/BF01971837

    authors： Somkuti SG,Abou-Donia MB

    更新日期：1990-01-01 00:00:00

  • Change of embryotoxic susceptibility to di-n-butyltin dichloride in cultured rat embryos.

    abstract：:Di-n-butylin dichloride (DBTCl), which is commonly used as heat and light stabilizer for polyvinyl chloride (PVC) plastics, is a teratogen in vivo. In the present study, the toxic effects were investigated of DBTCl on cultured rat embryos during three different stages of organogenesis. Rat embryos explanted on gestati...

    journal_title：Archives of toxicology

    pub_type： 杂志文章

    doi：10.1007/s002040050335

    authors： Ema M,Iwase T,Iwase Y,Ohyama N,Ogawa Y

    更新日期：1996-01-01 00:00:00

  • The mycotoxin patulin reacts with DNA bases with and without previous conjugation to GSH: implication for related α,β-unsaturated carbonyl compounds?

    abstract：:The α,β-unsaturated carbonyl group is recognized as alert for mutagenicity, attributed to (1) its direct reaction with DNA, counteractable by glutathione (GSH), and (2) oxidative stress caused indirectly by GSH depletion. Accordingly, the α,β,γ,δ-unsaturated lactone patulin (PAT), a mycotoxin detected in fruits and pr...

    journal_title：Archives of toxicology

    pub_type： 杂志文章

    doi：10.1007/s00204-014-1443-z

    authors： Pfenning C,Esch HL,Fliege R,Lehmann L

    更新日期：2016-02-01 00:00:00

  • Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on liver phosphoenolpyruvate carboxykinase (PEPCK) activity, glucose homeostasis and plasma amino acid concentrations in the most TCDD-susceptible and the most TCDD-resistant rat strains.

    abstract：:Reduced gluconeogenesis due to decreased activity of key gluconeogenic enzymes in liver, together with feed refusal, has been suggested to play an important role in 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD)-induced lethality in rats. This study was carried out to further analyse the toxicological significance of red...

    journal_title：Archives of toxicology

    pub_type： 杂志文章

    doi：10.1007/s002040050626

    authors： Viluksela M,Unkila M,Pohjanvirta R,Tuomisto JT,Stahl BU,Rozman KK,Tuomisto J

    更新日期：1999-08-01 00:00:00

  • Biochemical and toxicological effects of short-term, intermittent xylene inhalation exposure and combined ethanol intake.

    abstract：:Intermittent inhalation of 300 ppm of xylene vapour 6 h daily for 2 weeks caused a marked accumulation of the solvent in the perirenal fat. Simultaneous ethanol ingestion reduced the solvent load significantly although the perirenal xylene concentration increased in both test groups between the first and second week o...

    journal_title：Archives of toxicology

    pub_type： 杂志文章

    doi：10.1007/BF00354091

    authors： Savolainen H,Vainio H,Helojoki M,Elovaara E

    更新日期：1978-12-28 00:00:00

  • Sister chromatid exchange frequency in cultured isolated porcine urinary bladder epithelial cells (PUBEC) treated with ochratoxin A and alpha.

    abstract：:The mycotoxin ochratoxin A (OTA) and its metabolite ochratoxin alpha (OT-alpha) were investigated, to examine their potency to induce sister chromatid exchanges (SCE) in cultured porcine urinary bladder epithelial cells (PUBEC) (primary culture). Serum-free cultured PUBEC were incubated for 5 h with either OTA or OT-a...

    journal_title：Archives of toxicology

    pub_type： 杂志文章

    doi：10.1007/s002040050171

    authors： Föllmann W,Hillebrand IE,Creppy EE,Bolt HM

    更新日期：1995-01-01 00:00:00

  • Mutagenicity and cytotoxicity of 2-chlorobenzylidene malonitrile (CS) and metabolites in V79 Chinese hamster cells.

    abstract：:The genotoxicity of the sensory irritant 2-chlorobenzylidene malonitrile (CS) to V79 Chinese hamster cells was investigated using the induction of gene mutations, micronuclei and DNA repair synthesis as biological endpoints. CS efficiently induced micronuclei and mutants resistant to 6-thioguanine in these cells, but ...

    journal_title：Archives of toxicology

    pub_type： 杂志文章

    doi：10.1007/BF00278645

    authors： Ziegler-Skylakakis K,Summer KH,Andrae U

    更新日期：1989-01-01 00:00:00

  • The inhibitory effects of garlic and Panax ginseng extract standardized with ginsenoside Rg3 on the genotoxicity, biochemical, and histological changes induced by ethylenediaminetetraacetic acid in male rats.

    abstract：:Ethylenediaminetetraacetic acid (EDTA) is widely used in food and other industries to sequester metal ions and to prevent their disadvantageous effects. The objective of the current study was to evaluate the protective effect of Panax ginseng extract standardized with ginsenoside Rg3 (ginsenoside Rg3 content was 3.6% ...

    journal_title：Archives of toxicology

    pub_type： 杂志文章

    doi：10.1007/s00204-007-0237-y

    authors： Khalil WK,Ahmed KA,Park MH,Kim YT,Park HH,Abdel-Wahhab MA

    更新日期：2008-03-01 00:00:00

  • Toxicokinetics of soman in cerebrospinal fluid and blood of anaesthetized pigs.

    abstract：:The toxicokinetics of the four stereoisomers of the nerve agent C(+/-)P(+/-)-soman was analysed in cerebrospinal fluid (CSF) and blood in anaesthetized, spontaneously breathing pigs during a 90-min period after injection of soman. The pigs were challenged with different intravenous (i.v.) doses of C(+/-)P(+/-)-soman c...

    journal_title：Archives of toxicology

    pub_type： 杂志文章

    doi：10.1007/s002040050529

    authors： Göransson-Nyberg A,Fredriksson SA,Karlsson B,Lundström M,Cassel G

    更新日期：1998-07-01 00:00:00

  • Antioxidative and anti-carcinogenic activities of tea polyphenols.

    abstract：:Tea (Camellia sinensis, Theaceace), a popular beverage consumed world-wide, has been studied for its preventive effects against cancer as well as cardiovascular, neurodegenerative, and other diseases. Most of the proposed beneficial effects have been attributed to the polyphenolic compounds in tea, but the nature of t...

    journal_title：Archives of toxicology

    pub_type： 杂志文章,评审

    doi：10.1007/s00204-008-0372-0

    authors： Yang CS,Lambert JD,Sang S

    更新日期：2009-01-01 00:00:00

  • Testosterone hydroxylase in evaluating induction and suppression of murine CYP isoenzymes by fenarimol.

    abstract：:This study aimed to investigate the effect of single and repeated administration of fenarimol on murine liver, kidney and lung microsomal CYP-catalyzed drug metabolism. The modulation of the regio- and stereo-selective hydroxylation of testosterone by fenarimol was considered in evaluating cocarcinogenic properties. I...

    journal_title：Archives of toxicology

    pub_type： 杂志文章

    doi：10.1007/s002040050298

    authors： Paolini M,Pozzetti L,Mesirca R,Sapone A,Cantelli-Forti G

    更新日期：1996-01-01 00:00:00

  • Application of ESR spectroscopy in toxicology.

    abstract：:Spin trapping in vivo was first achieved in the author's laboratory and is shown to be a feasible method for demonstrating that highly reactive free radical intermediates are generated in the tissues of intact animals as a result of the exposure to certain toxic compounds and to ionizing radiation. The method is based...

    journal_title：Archives of toxicology

    pub_type： 杂志文章,评审

    doi：10.1007/BF00296966

    authors： McCay PB

    更新日期：1987-01-01 00:00:00

  • Detrimental effects of prenatal exposure to filtered diesel exhaust on mouse spermatogenesis.

    abstract：:We recently showed that prenatal exposure to diesel exhaust (DE) disrupts spermatogenesis in mouse offspring. This study was undertaken to determine whether filtered DE in which 99.97% of diesel exhaust particles >0.3 microm in diameter were removed affects spermatogenesis in growing mice. After prenatal exposure to f...

    journal_title：Archives of toxicology

    pub_type： 杂志文章

    doi：10.1007/s00204-008-0302-1

    authors： Ono N,Oshio S,Niwata Y,Yoshida S,Tsukue N,Sugawara I,Takano H,Takeda K

    更新日期：2008-11-01 00:00:00

  • Sirtuin-1 ameliorates cadmium-induced endoplasmic reticulum stress and pyroptosis through XBP-1s deacetylation in human renal tubular epithelial cells.

    abstract：:Cadmium (Cd), an occupational and environmental pollutant, induces nephrotoxicity by primarily damaging renal proximal tubular cells. In this study, we hypothesized that pyroptosis, a caspase-1-dependent inflammatory programmed cell death mechanism, mediates Cd-induced nephrotoxicity. Human proximal tubular epithelial...

    journal_title：Archives of toxicology

    pub_type： 杂志文章

    doi：10.1007/s00204-019-02415-8

    authors： Chou X,Ding F,Zhang X,Ding X,Gao H,Wu Q

    更新日期：2019-04-01 00:00:00

  • Human variability in isoform-specific UDP-glucuronosyltransferases: markers of acute and chronic exposure, polymorphisms and uncertainty factors.

    abstract：:UDP-glucuronosyltransferases (UGTs) are involved in phase II conjugation reactions of xenobiotics and differences in their isoform activities result in interindividual kinetic differences of UGT probe substrates. Here, extensive literature searches were performed to identify probe substrates (14) for various UGT isofo...

    journal_title：Archives of toxicology

    pub_type： 杂志文章

    doi：10.1007/s00204-020-02765-8

    authors： Kasteel EEJ,Darney K,Kramer NI,Dorne JLCM,Lautz LS

    更新日期：2020-08-01 00:00:00

  • Effect of direct infusion of acetaldehyde on dopamine and dopamine-derived salsolinol in the striatum of free-moving rats using a reverse microdialysis technique.

    abstract：:The effects of acetaldehyde (ACD) on dopamine (DA) and DA-derived salsolinol (SAL) levels were investigated in the striatum of freely moving rats. Dialysate levels of DA and SAL were determined using in vivo reverse microdialysis coupled with high-performance liquid chromatography with an electrochemical detector. Per...

    journal_title：Archives of toxicology

    pub_type： 杂志文章

    doi：10.1007/s00204-006-0131-z

    authors： Wang W,Ameno K,Jamal M,Kumihashi M,Uekita I,Ameno S,Ijiri I

    更新日期：2007-02-01 00:00:00

  • Sertoli cells proliferate in adult rats with prenatal exposure to 3,3',4,4',5-pentachlorobiphenyl.

    abstract：:Sertoli cells play a critical role in spermatogenesis, and in adults, they are terminally differentiated with loss of proliferative activity. This study revealed Sertoli cell proliferation in 17-week-old Sprague-Dawley rats whose dams had been intragastrically administered 250 ng of 3,3',4,4',5-pentachlorobiphenyl/kg ...

    journal_title：Archives of toxicology

    pub_type： 杂志文章

    doi：10.1007/s00204-011-0736-8

    authors： Wakui S,Muto T,Suzuki Y,Takahashi H,Hano H

    更新日期：2012-01-01 00:00:00

  • Cell death mechanisms of the anti-cancer drug etoposide on human cardiomyocytes isolated from pluripotent stem cells.

    abstract：:Etoposide (ETP) and anthracyclines are applied for wide anti-cancer treatments. However, the ETP-induced cardiotoxicity remains to be a major safety issue and the underlying cardiotoxic mechanisms are not well understood. This study is aiming to unravel the cardiotoxicity profile of ETP in comparison to anthracyclines...

    journal_title：Archives of toxicology

    pub_type： 杂志文章

    doi：10.1007/s00204-018-2170-7

    authors： Nemade H,Chaudhari U,Acharya A,Hescheler J,Hengstler JG,Papadopoulos S,Sachinidis A

    更新日期：2018-04-01 00:00:00

  • Ethylmorphine concentrations in human samples in an overdose case.

    abstract：:Capillary gas chromatography coupled to mass spectrometry was employed to quantify ethylmorphine in biological fluids and tissues in a death attributed to oral ethylmorphine ingestion. The femoral blood concentration of the drug was 488 ng/ml. Hair analysis revealed the individual's drug abuse pattern, particularly th...

    journal_title：Archives of toxicology

    pub_type： 信件

    doi：10.1007/s002040050057

    authors： Kintz P,Jamey C,Mangin P

    更新日期：1994-01-01 00:00:00

  • Mixture component effects on the in vitro dermal absorption of pentachlorophenol.

    abstract：:Interactions between chemicals in a mixture and interactions of mixture components with the skin can significantly alter the rate and extent of percutaneous absorption, as well as the cutaneous disposition of a topically applied chemical. The predictive ability of dermal absorption models, and consequently the dermal ...

    journal_title：Archives of toxicology

    pub_type： 杂志文章

    doi：10.1007/s002040100242

    authors： Riviere JE,Qiao G,Baynes RE,Brooks JD,Mumtaz M

    更新日期：2001-08-01 00:00:00

  • Maintenance of drug metabolism and transport functions in human precision-cut liver slices during prolonged incubation for 5 days.

    abstract：:Human precision-cut liver slices (hPCLS) are a valuable ex vivo model that can be used in acute toxicity studies. However, a rapid decline in metabolic enzyme activity limits their use in studies that require a prolonged xenobiotic exposure. The aim of the study was to extend the viability and function of hPCLS to 5 d...

    journal_title：Archives of toxicology

    pub_type： 杂志文章

    doi：10.1007/s00204-016-1865-x

    authors： Starokozhko V,Vatakuti S,Schievink B,Merema MT,Asplund A,Synnergren J,Aspegren A,Groothuis GMM

    更新日期：2017-05-01 00:00:00

  • Metabolomics reveals trichloroacetate as a major contributor to trichloroethylene-induced metabolic alterations in mouse urine and serum.

    abstract：:Trichloroethylene (TCE)-induced liver toxicity and carcinogenesis is believed to be mediated in part by activation of the peroxisome proliferator-activated receptor α (PPARα). However, the contribution of the two TCE metabolites, dichloroacetate (DCA) and trichloroacetate (TCA) to the toxicity of TCE, remains unclear....

    journal_title：Archives of toxicology

    pub_type： 杂志文章

    doi：10.1007/s00204-013-1053-1

    authors： Fang ZZ,Krausz KW,Tanaka N,Li F,Qu A,Idle JR,Gonzalez FJ

    更新日期：2013-11-01 00:00:00

  • Hair analysis for drugs of abuse. IV. Determination of total morphine and confirmation of 6-acetylmorphine in monkey and human hair by GC/MS.

    abstract：:The reliable analytical method for total morphine in hair was established by GC/MS-SIM. The calibration curve for morphine in hair showed linear over 0.5-100 ng/mg hair. Though the limit of detection was 0.1 ng/mg hair with an S/N > 3 of the base ion(m/z 429) for morphine, the limit of confirmation by detection of thr...

    journal_title：Archives of toxicology

    pub_type： 杂志文章

    doi：10.1007/BF01981507

    authors： Nakahara Y,Takahashi K,Shimamine M,Saitoh A

    更新日期：1992-01-01 00:00:00

  • Selected testicular enzymes as biochemical markers for procarbazine-induced testicular toxicity.

    abstract：:Single doses of procarbazine (MIH) were injected IP at 0, 50, 100, 200, and 400 mg/kg body weight to CD-1 male mice. Activities of hyaluronidase, lactate dehydrogenase isoenzyme-X, and the dehydrogenases of sorbitol, alpha-glycerophosphate, glucose-6-phosphate, malate, isocitrate, and glyceraldehyde-3-phosphate in the...

    journal_title：Archives of toxicology

    pub_type： 杂志文章

    doi：10.1007/BF00341017

    authors： Shen RS,Lee IP

    更新日期：1984-10-01 00:00:00

  • Cyclophosphamide effects on fetal mouse cephalic acetylcholinesterase.

    abstract：:Pregnant C3H mice were exposed to a teratogenic dose of cyclophosphamide (CP, 20 mg/kg body weight) on the 10th day after copulation. Embryos or fetuses were examined 2-9 days later for gross abnormalities, weighed, and assayed for cephalic acetylcholinesterase (EC 3.1.1.7, AChE) activity, and haemoglobin content. In ...

    journal_title：Archives of toxicology

    pub_type： 杂志文章

    doi：10.1007/BF00570147

    authors： Pillans PI,Stephenson BA,Folb PI

    更新日期：1988-01-01 00:00:00

  • Exposures to the environmental toxicants pentachlorophenol (PCP) and dichlorodiphenyltrichloroethane (DDT) modify secretion of interleukin 1-beta (IL-1β) from human immune cells.

    abstract：:Pentachlorophenol (PCP) and Dichlorodiphenyltrichloroethane (DDT) are environmental contaminants found in human blood. Previous studies have shown that PCP and DDT inhibit the lytic function of highly purified human natural killer (NK) lymphocytes and decrease the expression of several surface proteins on NK cells. In...

    journal_title：Archives of toxicology

    pub_type： 杂志文章

    doi：10.1007/s00204-016-1829-1

    authors： Martin TJ,Whalen MM

    更新日期：2017-04-01 00:00:00

  • Regulation of uterine AHR battery gene expression by 17β-Estradiol is predominantly mediated by estrogen receptor α.

    abstract：:The aryl hydrocarbon receptor (AHR) is known to mediate the cellular response to numerous xenobiotics including dioxin. Surprisingly AHR knockout mice provide evidence for the involvement of the AHR signalling cascade in estrogen regulated physiological functions of the female reproductive system. Several studies alre...

    journal_title：Archives of toxicology

    pub_type： 杂志文章

    doi：10.1007/s00204-012-0870-y

    authors： Rataj F,Möller FJ,Jähne M,Zierau O,Diel P,Vollmer G,Kretzschmar G

    更新日期：2012-10-01 00:00:00

  • Toluene concentrations in various tissues of rats after inhalation and oral administration.

    abstract：:The uptake, distribution, and elimination of 3H-toluene in various tissues of rats were studied after inhalation or after gastric intubation. The maximum radioactivity was measured 2--3 h after gastric intubation in tissues, except in white adipose tissue, where the peak radioactivity was reached at 5 h. After inhala...

    journal_title：Archives of toxicology

    pub_type： 杂志文章

    doi：10.1007/BF00293651

    authors： Pyykkö K,Tähti H,Vapaatalo H

    更新日期：1977-09-28 00:00:00