Comparative analysis of phase I and II enzyme activities in 5 hepatic cell lines identifies Huh-7 and HCC-T cells with the highest potential to study drug metabolism.

Abstract:

:Primary human hepatocytes (hHeps) are still gold standard to perform human drug metabolism studies, but their availability is limited by donor organ scarcity. Therefore, hepatoma cell lines are widely used as alternatives, although their phases I and II drug-metabolizing activities are substantially lower compared with hHeps. The major advantage of these cell lines is immediate availability, standardized culture conditions and unlimited life span. Therefore, the aim of this study was to investigate the drug-metabolizing profile of five human hepatoma cell lines (HepG2, Hep3B, HCC-T, HCC-M and Huh-7) over a culture period of 10 passages. Fluorescent-based assays for seven different cytochrome P450 (CYP) isoforms and seven different phase II enzymes were performed and compared with enzymatic activities of hHeps. CYP activities were much lower in the cell lines (5-15% of hHeps), whereas phase II enzyme activities that are involved in buffering oxidative stress (e.g., Glutathione-S-transferase) reached levels comparable with hHeps. Furthermore, phases I and II enzyme activities in hepatoma cell lines vary strongly during culture time. Interestingly, the most constant results were obtained with Huh-7 cells. Huh-7 cells as well as HCC-T cells exhibited a drug-metabolizing profile closest to hHeps between passages two and four. Toxicity studies with Diclofenac, Paracetamol and Verapamil in both cell lines show dose-response characteristics and EC(50) values similar to hHeps. Therefore, we propose that due to the more consistent results throughout the passages, Huh-7 could be an alternative system to the limitedly available hHeps and frequently used HepG2 cell line in the study of drug metabolism.

journal_name

Arch Toxicol

journal_title

Archives of toxicology

authors

Lin J,Schyschka L,Mühl-Benninghaus R,Neumann J,Hao L,Nussler N,Dooley S,Liu L,Stöckle U,Nussler AK,Ehnert S

doi

10.1007/s00204-011-0733-y

subject

Has Abstract

pub_date

2012-01-01 00:00:00

pages

87-95

issue

1

eissn

0340-5761

issn

1432-0738

journal_volume

86

pub_type

杂志文章
  • Induction of peroxisomal beta-oxidation and P-450 4A-dependent activities by pivalic and trichloroacetic acid in rat liver and kidney.

    abstract::The influence of pivalic acid (PIV), a compound often used to make pro-drugs, and of the structurally related trichloroacetic acid (TCA), on several hepatic and renal enzymes was investigated in Sprague-Dawley rats, following a 4-day treatment period. The PIV and TCA treatments resulted in a similar and selective indu...

    journal_title:Archives of toxicology

    pub_type: 杂志文章

    doi:10.1007/s002040050253

    authors: Zanelli U,Puccini P,Acerbi D,Ventura P,Gervasi PG

    更新日期:1996-01-01 00:00:00

  • Antibiotic resistance mechanisms in M. tuberculosis: an update.

    abstract::Treatment of tuberculosis (TB) has been a therapeutic challenge because of not only the naturally high resistance level of Mycobacterium tuberculosis to antibiotics but also the newly acquired mutations that confer further resistance. Currently standardized regimens require patients to daily ingest up to four drugs un...

    journal_title:Archives of toxicology

    pub_type: 杂志文章,评审

    doi:10.1007/s00204-016-1727-6

    authors: Nguyen L

    更新日期:2016-07-01 00:00:00

  • Metabolism of acrylamide to glycidamide and their cytotoxicity in isolated rat hepatocytes: protective effects of GSH precursors.

    abstract::Acrylamide (AA) is a widely studied industrial chemical that is neurotoxic, mutagenic to somatic and germ cells, and carcinogenic in rodents. The recent discovery of AA at ppm levels in a wide variety of commonly consumed foods has energized research efforts worldwide to define toxicity and prevention. Metabolism and ...

    journal_title:Archives of toxicology

    pub_type: 杂志文章

    doi:10.1007/s00204-006-0109-x

    authors: Kurebayashi H,Ohno Y

    更新日期:2006-12-01 00:00:00

  • Study on the mechanism of photosensitive dermatitis caused by ketoprofen in the guinea pig.

    abstract::To investigate the mechanism on photosensitive dermatitis caused by ketoprofen (KP) in humans, the following experiments were performed by topical application on guinea pigs. The phototoxicity study involving treatment with 10% solution of KP, its enantiomers (R-KP and S-KP), loxoprofen, and flurbiprofen revealed no p...

    journal_title:Archives of toxicology

    pub_type: 杂志文章

    doi:10.1007/s00204-006-0063-7

    authors: Nakazawa T,Shimo T,Chikamatsu N,Igarashi T,Nagata O,Yamamoto M

    更新日期:2006-07-01 00:00:00

  • Toxicology of organophosphorus compounds in view of an increasing terrorist threat.

    abstract::The implementation of the Chemical Weapon Convention (CWC), prohibiting the development, production, storage and use of chemical weapons by 192 nations and the ban of highly toxic OP pesticides, especially class I pesticides according to the WHO classification, by many countries constitutes a great success of the inte...

    journal_title:Archives of toxicology

    pub_type: 杂志文章,评审

    doi:10.1007/s00204-016-1772-1

    authors: Worek F,Wille T,Koller M,Thiermann H

    更新日期:2016-09-01 00:00:00

  • Omnisphero: a high-content image analysis (HCA) approach for phenotypic developmental neurotoxicity (DNT) screenings of organoid neurosphere cultures in vitro.

    abstract::Current developmental neurotoxicity (DNT) testing in animals faces major limitations, such as high cost and time demands as well as uncertainties in their methodology, evaluation and regulation. Therefore, the use of human-based 3D in vitro systems in combination with high-content image analysis (HCA) might contribute...

    journal_title:Archives of toxicology

    pub_type: 杂志文章

    doi:10.1007/s00204-016-1852-2

    authors: Schmuck MR,Temme T,Dach K,de Boer D,Barenys M,Bendt F,Mosig A,Fritsche E

    更新日期:2017-04-01 00:00:00

  • Effect of cadmium or magnesium on calcium-dependent central function that reduces blood pressure.

    abstract::The effect of intracerebroventricular (i.c.v.) administration of cadmium or magnesium on central calcium-dependent blood pressure regulation was investigated. The systolic blood pressure of spontaneously hypertensive rats (SHR; male, 13 weeks of age) decreased following i.c.v. administration of cadmium chloride (20 nm...

    journal_title:Archives of toxicology

    pub_type: 杂志文章

    doi:10.1007/s002040050644

    authors: Sutoo D,Akiyama K

    更新日期:2000-03-01 00:00:00

  • High blood pressure is one of the symptoms of paraquat-induced toxicity in rats.

    abstract::This study investigated whether paraquat (Pq)-induced lipidic peroxidation (LP) is accompanied by changes in blood pressure and heart rate (HR) in rats. Groups of adult male Wistar rats were studied 2 and 12 h after Pq (35 mg/kg, i.p.) administration. The LP was evaluated by monitoring thiobarbituric acid reactive sub...

    journal_title:Archives of toxicology

    pub_type: 杂志文章

    doi:10.1007/s00204-005-0660-x

    authors: Oliveira MV,Albuquerque JA,Paixão AD,Guedes LS,Cabral AM

    更新日期:2005-09-01 00:00:00

  • Neurochemical changes in rats coexposed to lead and copper.

    abstract::Rats were coexposed to lead (Pb) and Copper (Cu) through drinking water and intraperitoneally, respectively, for a period of 21 days. Neurochemical studies in these rats showed significant reduction in the activity of adenosine triphosphatase, cytochrome-c-oxidase, diaphorase and in the levels of biogenic amines in th...

    journal_title:Archives of toxicology

    pub_type: 杂志文章

    doi:10.1007/BF00347881

    authors: Malhotra KM,Shukla GS,Chandra SV

    更新日期:1982-03-01 00:00:00

  • Reduction and binding of arsenate in marmoset monkeys.

    abstract::The metabolism of 74As-arsenate (As V, 0.4 mg As/kg body weight, IV) in marmoset monkeys (two males and two females) was studied. Unlike all other animal species studied so far, the marmoset was found to be unable to metabolize the arsenate to dimethylarsinic acid. Most of the absorbed arsenate was reduced to arsenite...

    journal_title:Archives of toxicology

    pub_type: 杂志文章

    doi:10.1007/BF00343121

    authors: Vahter M,Marafante E

    更新日期:1985-06-01 00:00:00

  • Characterization of the tobacco glycoprotein surface binding property of heart and skeletal muscle cells. I. Modulation of the heart cell membrane TGP interaction by anti-TGP IgG.

    abstract::Monolayers of L6 rat skeletal myoblast cells formed surface binding isotherms with the purified tobacco leaf glycoprotein TGP1 and the enriched cigarette tar glycoprotein TGP2. Scatchard analysis showed that the binding in the range of the limited concentrations tested was to a single class molecule and the calculated...

    journal_title:Archives of toxicology

    pub_type: 杂志文章

    doi:10.1007/s002040050151

    authors: Santos-Buch CA,Hall HR,Farfan F,Orlow I,Firpo A,von Kreuter BF,Becker CG

    更新日期:1995-01-01 00:00:00

  • Inflammatory responses induced by fluoride and arsenic at toxic concentration in rabbit aorta.

    abstract::Epidemiological and experimental studies have demonstrated the atherogenic effects of environmental toxicant arsenic and fluoride. Inflammatory mechanism plays an important role in the pathogenesis of atherosclerosis. The aim of the present study is to determine the effect of chronic exposure to arsenic and fluoride a...

    journal_title:Archives of toxicology

    pub_type: 杂志文章

    doi:10.1007/s00204-012-0803-9

    authors: Ma Y,Niu R,Sun Z,Wang J,Luo G,Zhang J,Wang J

    更新日期:2012-06-01 00:00:00

  • Use of the dog as non-rodent test species in the safety testing schedule associated with the registration of crop and plant protection products (pesticides): present status.

    abstract::The results from a survey of the expert information that is publicly accessible on the use of the dog as test species during the regulatory evaluation of agricultural chemicals and pesticides are reported. Methods that are being used or considered in order to reduce the number of dogs used for this purpose are describ...

    journal_title:Archives of toxicology

    pub_type: 杂志文章

    doi:10.1007/s00204-005-0678-0

    authors: Box RJ,Spielmann H

    更新日期:2005-11-01 00:00:00

  • Suppression of erythropoietin gene expression by cadmium depends on inhibition of HIF-1, not stimulation of GATA-2.

    abstract::Long-term exposure of rats to cadmium (Cd) resulted in a marked suppression of erythropoietin (Epo) mRNA expression in the kidneys and the development of severe anemia. A recent report revealed that Cd inhibited hypoxia-inducible factor 1 (HIF-1) binding activity and Epo mRNA expression and protein production. However...

    journal_title:Archives of toxicology

    pub_type: 杂志文章

    doi:10.1007/s00204-003-0444-0

    authors: Obara N,Imagawa S,Nakano Y,Suzuki N,Yamamoto M,Nagasawa T

    更新日期:2003-05-01 00:00:00

  • Toxicology data of graphene-family nanomaterials: an update.

    abstract::Due to its unique physical structure and chemical properties, graphene family nanomaterials (GFNs) and derived commodities have been widely used in commercial products, particularly biomedical applications, which has significantly increased the risk of human exposure. There exists significant evidence that GFNs are ac...

    journal_title:Archives of toxicology

    pub_type: 杂志文章,评审

    doi:10.1007/s00204-020-02717-2

    authors: Xiaoli F,Qiyue C,Weihong G,Yaqing Z,Chen H,Junrong W,Longquan S

    更新日期:2020-06-01 00:00:00

  • Induction of monooxygenases and growth in rat liver by progesterone.

    abstract::Female Wistar rats were treated with various doses of progesterone orally via the diet or via the SC route. Oral treatment resulted in enhanced progesterone levels in the liver as measured by radioimmunoassay. There were up to 3-fold increases in activity of ethylmorphine demethylation by isolated microsomes; metaboli...

    journal_title:Archives of toxicology

    pub_type: 杂志文章

    doi:10.1007/BF00316323

    authors: Ochs H,Düsterberg B,Schulte-Hermann R

    更新日期:1986-10-01 00:00:00

  • A physiologically based pharmacokinetic model for the oxime TMB-4: simulation of rodent and human data.

    abstract::Multiple oximes have been synthesized and evaluated for use as countermeasures against chemical warfare nerve agents. The current U.S. military and civilian oxime countermeasure, 2-[(hydroxyimino)methyl]-1-methylpyridin-1-ium chloride (2-PAM), is under consideration for replacement with a more effective acetylcholines...

    journal_title:Archives of toxicology

    pub_type: 杂志文章

    doi:10.1007/s00204-012-0987-z

    authors: Sterner TR,Ruark CD,Covington TR,Yu KO,Gearhart JM

    更新日期:2013-04-01 00:00:00

  • Association between polymorphism of GSTP1, GSTT1, GSTM1 and CYP2E1 genes and susceptibility to benzene-induced hematotoxicity.

    abstract::Occupational exposure to benzene has been associated with leukemia, anemia, leukopenia, and thrombocytopenia. Genetic susceptibility to benzene toxicity in humans may be related to variations in benzene metabolizing genes. The main objective of this study was to ascertain whether polymorphism of GSTP1, GSTM1, GSTT1 an...

    journal_title:Archives of toxicology

    pub_type: 杂志文章

    doi:10.1007/s00204-017-2104-9

    authors: Nourozi MA,Neghab M,Bazzaz JT,Nejat S,Mansoori Y,Shahtaheri SJ

    更新日期:2018-06-01 00:00:00

  • Toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in cold-adapted rats.

    abstract::The toxicity of 60 micrograms/kg 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) given IP in corn oil/5% acetone was examined in male Sprague-Dawley rats adapted to 25 degrees C or 4 degrees C ambient temperature. Cold exposure significantly reduced mean time to death and tended to increase mortality. Body weight at the ti...

    journal_title:Archives of toxicology

    pub_type: 杂志文章

    doi:10.1007/BF00290540

    authors: Rozman K,Greim H

    更新日期:1986-12-01 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

  • Effect of acute and chronic cadmium treatment on hepatic drug metabolism in male rats.

    abstract::The effect of acute and chronic cadmium administration on hepatic drug metabolism was investigated in the male rat. 3 days after the acute administration of cadmium by either the intraperitoneal (0.84 mg Cd/kg) or the oral (greater than 80 mg Cd/kg) route, there was a significant potentiation in duration of hexobarbit...

    journal_title:Archives of toxicology

    pub_type: 杂志文章

    doi:10.1007/BF00310332

    authors: Schnell RC,Yuhas EM,Pence DH,Means JR,Roberts SA,Yau ET,Miya TS,Mennear JH

    更新日期:1978-08-09 00:00:00

  • Prenatal effects of trichlorfon on the guinea pig brain.

    abstract::The organophosphorus compound trichlorfon, dimethyl (2,2,2-trichloro-1-hydroxyethyl) phosphonate, was administered by stomach tube (100 mg/kg) to pregnant guinea pigs at two different stages of gestation (days 36, 37, 38 and 51, 52, 53). The pups developed locomotory disturbances, and post mortem examination revealed ...

    journal_title:Archives of toxicology

    pub_type: 杂志文章

    doi:10.1007/BF00263954

    authors: Berge GN,Nafstad I,Fonnum F

    更新日期:1986-05-01 00:00:00

  • Nephrotoxicity of 4-cycloocten-1-carbaldehyde.

    abstract::Natural and synthetic chemicals are often used in the fragrance industry. A toxicological profile of the synthetic fragrance booster, 4-cycloocten-1-carbaldehyde, was generated using a test program including the following methods: acute oral toxicity, acute dermal toxicity, acute skin and eye irritation, skin sensitiz...

    journal_title:Archives of toxicology

    pub_type: 杂志文章

    doi:10.1007/s00204-004-0596-6

    authors: Messinger H,Kleber M,Aulmann W

    更新日期:2004-12-01 00:00:00

  • Deficit in learning and memory of rats with chronic fluorosis correlates with the decreased expressions of M1 and M3 muscarinic acetylcholine receptors.

    abstract::To reveal the molecular mechanism of deficit in learning and memory induced by chronic fluorosis, the expression of muscarinic acetylcholine receptors (mAChRs) and oxidative stress were investigated. Sixty Sprague-Dawley (SD) rats were divided randomly into two groups (30 cases in each), i.e., the control group (<0.5 ...

    journal_title:Archives of toxicology

    pub_type: 杂志文章

    doi:10.1007/s00204-014-1408-2

    authors: Dong YT,Wang Y,Wei N,Zhang QF,Guan ZZ

    更新日期:2015-11-01 00:00:00

  • AhR-mediated changes in global gene expression in rat liver progenitor cells.

    abstract::Although the tumor-promoting effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), coplanar polychlorinated biphenyls (PCBs), and related compounds in liver tissue are primarily attributed to the activation of the aryl hydrocarbon receptor (AhR), the underlying molecular mechanisms are still unclear. Liver progenitor...

    journal_title:Archives of toxicology

    pub_type: 杂志文章

    doi:10.1007/s00204-012-0979-z

    authors: Faust D,Vondráček J,Krčmář P,Smerdová L,Procházková J,Hrubá E,Hulinková P,Kaina B,Dietrich C,Machala M

    更新日期:2013-04-01 00:00:00

  • Chelation in metal intoxication. XII. Antidotal efficacy of chelating agents on acute toxicity of manganese.

    abstract::Several structurally different metal chelating agents were screened for their relative efficacy in counteracting acute manganese intoxication in mice. Polyaminocarboxylic acids with nitrogen and oxygen as metal binding sites were more effective than certain sulfhydryl chelating agents and common drugs in preventing mo...

    journal_title:Archives of toxicology

    pub_type: 杂志文章

    doi:10.1007/BF00569233

    authors: Tandon SK,Khandelwal S

    更新日期:1982-05-01 00:00:00

  • Tamoxifen induces hepatocellular carcinoma in rat liver: a 1-year study with two antiestrogens.

    abstract::The effects of equimolar doses of the triphenylethylene antiestrogens tamoxifen and toremifene on female Sprague-Dawley rat liver were studied in a 52-week toxicity study which included a 13-week recovery period. Liver tumors were found in four out of five rats at the highest dose level of tamoxifen (45 mg/kg per day)...

    journal_title:Archives of toxicology

    pub_type: 杂志文章

    doi:10.1007/BF02072035

    authors: Hirsimäki P,Hirsimäki Y,Nieminen L,Payne BJ

    更新日期:1993-01-01 00:00:00

  • Hydrogen peroxide production in mouse tissues after acute d-amphetamine administration. Influence of monoamine oxidase inhibition.

    abstract::The toxicity of amphetamines is conditioned by a complex array of mechanisms, involving the increase of neurotransmission (e.g. leading to hyperthermia) and enzymatic and non-enzymatic oxidation of amphetamines and biogenic amines. Considering that all these processes may increase the generation of hydrogen peroxide (...

    journal_title:Archives of toxicology

    pub_type: 杂志文章

    doi:10.1007/s002040100264

    authors: Carvalho F,Duarte JA,Neuparth MJ,Carmo H,Fernandes E,Remião F,Bastos ML

    更新日期:2001-10-01 00:00:00

  • Experimental manganese lymphadenopathy in guinea pigs.

    abstract::Experimental manganese lymphadenopathy was produced by guinea pigs by intratracheal inoculation of manganese dioxide (50 mg/300 g body weight) and histopathologic changes in the tracheobronchial lymph nodes were studied up to 180 days. There was slow extracellular transport of manganese dust into the nodes, which did ...

    journal_title:Archives of toxicology

    pub_type: 杂志文章

    doi:10.1007/BF00351975

    authors: Shanker R,Dogra RK,Sahu AP,Zaidi SH

    更新日期:1976-10-28 00:00:00

  • Induction of Dectin-1 and asthma-associated signal transduction pathways in RAW 264.7 cells by a triple-helical (1, 3)-β-D glucan, curdlan.

    abstract::People living in damp buildings are typically exposed to spore and mycelial fragments of the fungi that grow on damp building materials. There is experimental evidence that this exposure to triple-helical (1, 3)-β-D glucan and low molecular weight toxins may be associated with non-atopic asthma observed in damp and mo...

    journal_title:Archives of toxicology

    pub_type: 杂志文章

    doi:10.1007/s00204-013-1042-4

    authors: Rand TG,Robbins C,Rajaraman D,Sun M,Miller JD

    更新日期:2013-10-01 00:00:00