当前位置： SCI文献检索 > TOXICOLOGY AND APPLIED PHARMACOLOGY期刊下所有文献 > Knockout of the aryl hydrocarbon receptor results in distinct hepatic and renal phenotypes in rats and mice.

Knockout of the aryl hydrocarbon receptor results in distinct hepatic and renal phenotypes in rats and mice.

Abstract：

:The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor which plays a role in the development of multiple tissues and is activated by a large number of ligands, including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). In order to examine the roles of the AHR in both normal biological development and response to environmental chemicals, an AHR knockout (AHR-KO) rat model was created and compared with an existing AHR-KO mouse. AHR-KO rats harboring either 2-bp or 29-bp deletion mutation in exon 2 of the AHR were created on the Sprague-Dawley genetic background using zinc-finger nuclease (ZFN) technology. Rats harboring either mutation type lacked expression of AHR protein in the liver. AHR-KO rats were also insensitive to thymic involution, increased hepatic weight and the induction of AHR-responsive genes (Cyp1a1, Cyp1a2, Cyp1b1, Ahrr) following acute exposure to 25 μg/kg TCDD. AHR-KO rats had lower basal expression of transcripts for these genes and also accumulated ~30-45-fold less TCDD in the liver at 7 days post-exposure. In untreated animals, AHR-KO mice, but not AHR-KO rats, had alterations in serum analytes indicative of compromised hepatic function, patent ductus venosus of the liver and persistent hyaloid arteries in the eye. AHR-KO rats, but not AHR-KO mice, displayed pathological alterations to the urinary tract: bilateral renal dilation (hydronephrosis), secondary medullary tubular and uroepithelial degenerative changes and bilateral ureter dilation (hydroureter). The present data indicate that the AHR may play significantly different roles in tissue development and homeostasis and toxicity across rodent species.

journal_name

Toxicol Appl Pharmacol

journal_title

Toxicology and applied pharmacology

authors

Harrill JA,Hukkanen RR,Lawson M,Martin G,Gilger B,Soldatow V,Lecluyse EL,Budinsky RA,Rowlands JC,Thomas RS

doi

10.1016/j.taap.2013.06.024

subject

Has Abstract

pub_date

2013-10-15 00:00:00

pages

503-18

issue

2

eissn

0041-008X

issn

1096-0333

pii

S0041-008X(13)00297-4

journal_volume

272

pub_type

杂志文章

相关文献

TOXICOLOGY AND APPLIED PHARMACOLOGY文献大全
  • Protective effects of antioxidants and anti-inflammatory agents against manganese-induced oxidative damage and neuronal injury.

    abstract：:Exposure to excessive manganese (Mn) levels leads to neurotoxicity, referred to as manganism, which resembles Parkinson's disease (PD). Manganism is caused by neuronal injury in both cortical and subcortical regions, particularly in the basal ganglia. The basis for the selective neurotoxicity of Mn is not yet fully un...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.taap.2011.06.001

    authors： Milatovic D,Gupta RC,Yu Y,Zaja-Milatovic S,Aschner M

    更新日期：2011-11-01 00:00:00

  • Sex-related differences in mouse renal metabolism and toxicity of acetaminophen.

    abstract：:The objective of this study is to elucidate the role of cytochrome P450 2E1 in the metabolic activation of acetaminophen (APAP) in mouse kidneys. With the kidney microsomes from C3H/HeJ mice, a significant sex-related difference was observed in the NADPH-dependent formation of a reactive APAP metabolite which was trap...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1006/taap.1993.1167

    authors： Hu JJ,Lee MJ,Vapiwala M,Reuhl K,Thomas PE,Yang CS

    更新日期：1993-09-01 00:00:00

  • Toxicology and pharmacokinetics of DTGM, a fusion toxin consisting of a truncated diphtheria toxin (DT388) linked to human granulocyte-macrophage colony-stimulating factor, in cynomolgus monkeys.

    abstract：:We developed a fusion toxin consisting of the catalytic and translocation domains of diphtheria toxin linked to human granulocyte-macrophage colony-stimulating factor (GM-CSF) (DTGM) for the treatment of patients with acute myeloid leukemia (AML). Our goal in this study was to determine the toxicity and pharmacokineti...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1006/taap.1999.8691

    authors： Hotchkiss CE,Hall PD,Cline JM,Willingham MC,Kreitman RJ,Gardin J,Latimer A,Ramage J,Feely T,DeLatte S,Tagge EP,Frankel AE

    更新日期：1999-07-15 00:00:00

  • NF-κB-regulation of miR-155, via SOCS1/STAT3, is involved in the PM2.5-accelerated cell cycle and proliferation of human bronchial epithelial cells.

    abstract：:Air pollution, especially fine particulate matter (PM2.5, particles <2.5 μm in size), induces adverse health effects on the respiratory system. Uncontrolled proliferation of bronchial epithelial cells, resulting from deregulated cell cycle progression, contributes to pulmonary homeostatic imbalance. Although dysregula...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.taap.2019.114616

    authors： Xiao T,Ling M,Xu H,Luo F,Xue J,Chen C,Bai J,Zhang Q,Wang Y,Bian Q,Liu Q

    更新日期：2019-08-15 00:00:00

  • Induction of cytokine mRNAs in mice after oral exposure to the trichothecene vomitoxin (deoxynivalenol): relationship to toxin distribution and protein synthesis inhibition.

    abstract：:The effects of oral exposure to 0, 5, and 25 mg/kg body wt vomitoxin (VT) on cytokine mRNA levels in spleen, Peyer's patches (PP), liver, kidney, and small intestine were evaluated in B6C3F1 mice at 2 and 4 hr postexposure using RT-PCR in conjunction with Southern hybridization analysis. The abundance of mRNAs for sev...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1006/taap.1995.1132

    authors： Azcona-Olivera JI,Ouyang Y,Murtha J,Chu FS,Pestka JJ

    更新日期：1995-07-01 00:00:00

  • Placental transfer and fetal distribution of fluoxetine in the rat.

    abstract：:Previously conducted reproduction and teratology studies in rats (unpublished observations) exposed to fluoxetine have revealed no compound-related adverse effects on fertility and no teratogenic effects. In order to confirm embryonic/fetal exposure to fluoxetine and/or metabolites, dissection and whole-body autoradio...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1016/0041-008x(89)90225-1

    authors： Pohland RC,Byrd TK,Hamilton M,Koons JR

    更新日期：1989-04-01 00:00:00

  • Online monitoring of cell metabolism for studying pharmacodynamic effects.

    abstract：:To characterize modes of action of substances and their cytotoxic effects Bionas GmbH has developed a new screening system to allow the continuous recording of how an active substance can act (Bionas 2500 analyzing system). In the pharmaceutical industry it is important to acquire as much information as possible about...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.taap.2006.12.027

    authors： Thedinga E,Kob A,Holst H,Keuer A,Drechsler S,Niendorf R,Baumann W,Freund I,Lehmann M,Ehret R

    更新日期：2007-04-01 00:00:00

  • Neurotoxic injury pathways in differentiated mouse motor neuron-neuroblastoma hybrid (NSC-34D) cells in vitro--limited effect of riluzole on thapsigargin, but not staurosporine, hydrogen peroxide and homocysteine neurotoxicity.

    abstract：:The neuroblastoma-spinal motor neuron fusion cell line, NSC-34, in its differentiated form, NSC-34D, permits examining the effects of riluzole, a proven treatment for amyotrophic lateral sclerosis (ALS) on cell death induction by staurosporine (STS), thapsigargin (Thaps), hydrogen peroxide (H(2)O(2)) and homocysteine ...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.taap.2011.10.022

    authors： Hemendinger RA,Armstrong EJ 3rd,Radio N,Brooks BR

    更新日期：2012-01-15 00:00:00

  • Lactate dehydrogenase isoenzymes in hamster lung lavage fluid after lung injury.

    abstract：:Lactate Dehydrogenase Isoenzymes in Hamster Lung Lavage Fluid after Lung Injury. Beck, B. D., Gerson, B., Feldman, H. A., and Brain, J. D. (1983). Toxicol. Appl. Pharmacol. 71, 59-71. Lactate dehydrogenase (LD) levels and isoenzyme patterns were determined in the cell-free supernatant fractions of lung lavage fluid fr...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1016/0041-008x(83)90045-5

    authors： Beck BD,Gerson B,Feldman HA,Brain JD

    更新日期：1983-10-01 00:00:00

  • Protection by clonidine from the cardiovascular changes and lethality following soman administration in the rat: role of brain acetylcholine.

    abstract：:The organophosphate cholinesterase inhibitor soman produced a dramatic increase in arterial blood pressure of up to 60 mm Hg in the unanesthetized rat with variable changes in heart rate. Pretreatment with clonidine resulted in a dose-related inhibition of soman-induced cardiovascular changes and enhanced the time of ...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1016/0041-008x(88)90364-x

    authors： Magrí V,Buccafusco JJ,Aronstam RS

    更新日期：1988-09-30 00:00:00

  • Mechanism of inhibition of lysyl hydroxylase activity by the organophosphates malathion and malaoxon.

    abstract：:Direct inhibition of lysyl hydroxylase by malathion and malaoxon was observed in an in vitro enzyme assay with recombinant lysyl hydroxylase expressed via a baculoviral system. The IC50 values for malathion and malaoxon were estimated to be approximately 60 and 45 mM, respectively. Additional kinetic studies showed th...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1006/taap.2001.9275

    authors： Samimi A,Last JA

    更新日期：2001-11-01 00:00:00

  • A mathematical model of production, distribution, and metabolism of melatonin in mammalian systems.

    abstract：:Melatonin is a neuroendocrine hormone which is currently receiving considerable attention as a treatment for jet lag, a treatment for insomnia and, by some, a possible "magic bullet" for delaying the effects of aging and preventing cancer. Production of melatonin is focused primarily in the pineal gland with very wide...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1006/taap.1997.8247

    authors： Blumenthal GM,Kohn MC,Portier CJ

    更新日期：1997-11-01 00:00:00

  • Toxicity and kinetics of [3H]microcystin-LR in isolated perfused rat livers.

    abstract：:Isolated rat livers were perfused for 60 min with either 0.3 or 0.5 microgram/ml (initial volume, 119 ml) of [3H]microcystin-LR at a constant flow of 10 ml/min in a recirculating system. During the 60-min exposure, toxin caused stimulation of glycogenolysis, liver engorgement, and cessation of bile flow. Electron micr...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1016/0041-008x(91)90303-v

    authors： Pace JG,Robinson NA,Miura GA,Matson CF,Geisbert TW,White JD

    更新日期：1991-03-01 00:00:00

  • A metabonomic evaluation of the monocrotaline-induced sinusoidal obstruction syndrome (SOS) in rats.

    abstract：:The main curative treatment of colorectal cancer remains the surgery. However, when metastases are suspected, surgery is followed by a preventive chemotherapy using oxaliplatin which, unfortunately, may cause liver sinusoidal obstruction syndrome (SOS). Such hepatic damage is barely detected during or after chemothera...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.taap.2014.02.008

    authors： Conotte R,Colet JM

    更新日期：2014-04-15 00:00:00

  • Adjuvant effect of respiratory irritation on pulmonary allergic sensitization: time and site dependency.

    abstract：:It has been suggested that airway irritation, by acting as an adjuvant, as well as producing damage, may be an important factor related to asthma. The present study examined the window of time following acute upper and lower airway irritant exposure to determine the period of increased risk of immunological sensitizat...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1006/taap.1997.8148

    authors： Siegel PD,Al-Humadi NH,Nelson ER,Lewis DM,Hubbs AF

    更新日期：1997-06-01 00:00:00

  • Evaluation of the interindividual human variation in bioactivation of methyleugenol using physiologically based kinetic modeling and Monte Carlo simulations.

    abstract：:The present study aims at predicting the level of formation of the ultimate carcinogenic metabolite of methyleugenol, 1'-sulfooxymethyleugenol, in the human population by taking variability in key bioactivation and detoxification reactions into account using Monte Carlo simulations. Depending on the metabolic route, v...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.taap.2014.12.009

    authors： Al-Subeihi AA,Alhusainy W,Kiwamoto R,Spenkelink B,van Bladeren PJ,Rietjens IM,Punt A

    更新日期：2015-03-01 00:00:00

  • Gene expression profiling and pathway analysis of human bronchial epithelial cells exposed to airborne particulate matter collected from Saudi Arabia.

    abstract：:Epidemiological studies have established a positive correlation between human mortality and increased concentration of airborne particulate matters (PM). However, the mechanisms underlying PM related human diseases, as well as the molecules and pathways mediating the cellular response to PM, are not fully understood. ...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.taap.2012.10.008

    authors： Sun H,Shamy M,Kluz T,Muñoz AB,Zhong M,Laulicht F,Alghamdi MA,Khoder MI,Chen LC,Costa M

    更新日期：2012-12-01 00:00:00

  • Oxidative stress and hepatic stellate cell activation are key events in arsenic induced liver fibrosis in mice.

    abstract：:Arsenic is an environmental toxicant and carcinogen. Exposure to arsenic is associated with development of liver fibrosis and portal hypertension through ill defined mechanisms. We evaluated hepatic fibrogenesis after long term arsenic exposure in a murine model. BALB/c mice were exposed to arsenic by daily gavages of...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.taap.2010.11.016

    authors： Ghatak S,Biswas A,Dhali GK,Chowdhury A,Boyer JL,Santra A

    更新日期：2011-02-15 00:00:00

  • Protective effects of melittin on transforming growth factor-β1 injury to hepatocytes via anti-apoptotic mechanism.

    abstract：:Melittin is a cationic, hemolytic peptide that is the main toxic component in the venom of the honey bee (Apis mellifera). Melittin has multiple effects, including anti-bacterial, anti-viral and anti-inflammatory, in various cell types. However, the anti-apoptotic mechanisms of melittin have not been fully elucidated ...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.taap.2011.08.012

    authors： Lee WR,Park JH,Kim KH,Park YY,Han SM,Park KK

    更新日期：2011-10-15 00:00:00

  • 2,3,7,8-Tetrachlorodibenzo-p-dioxin metabolism and disposition in yellow perch.

    abstract：:Accumulation, tissue distribution, and depuration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-derived 3H were examined in fingerling yellow perch fed a diet containing 494 ppt of [3H]TCDD for 13 weeks followed by the same diet without TCDD for 13 weeks. None of the TCDD-exposed perch showed any signs of overt toxici...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1016/0041-008x(86)90222-x

    authors： Kleeman JM,Olson JR,Chen SM,Peterson RE

    更新日期：1986-05-01 00:00:00

  • Role of 3,4-dichlorophenyl methyl sulfone, a metabolite of o-dichlorobenzene, in the changes in hepatic microsomal drug-metabolizing enzymes caused by o-dichlorobenzene administration in rats.

    abstract：:2,3- and 3,4-Dichlorophenyl methyl sulfoxides and 2,3- and 3,4-dichlorophenyl methyl sulfones (2,3- and 3,4-DCPSO2Mes) were detected in the urine of rats administered o-dichlorobenzene (o-DCB). After administration of o-DCB to rats, swift decreases were observed in the concentrations of o-DCB in blood, liver, and kidn...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1006/taap.1997.8191

    authors： Kato Y,Kimura R

    更新日期：1997-08-01 00:00:00

  • Mass spectrometry in identification of ecotoxicants including chemical and biological warfare agents.

    abstract：:Mass spectrometry is a unique tool to detect and identify trace levels of organic and bioorganic compounds as well as microorganisms in the environment. The range of potential chemical warfare (CW) and biological warfare (BW) agents is very broad. An important advantage of mass spectrometry over other techniques invol...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章,评审

    doi：10.1016/j.taap.2005.02.040

    authors： Lebedev AT

    更新日期：2005-09-01 00:00:00

  • Ethambutol-induced toxicity is mediated by zinc and lysosomal membrane permeabilization in cultured retinal cells.

    abstract：:Ethambutol, an efficacious antituberculosis agent, can cause irreversible visual loss in a small but significant fraction of patients. However, the mechanism of ocular toxicity remains to be established. We previously reported that ethambutol caused severe vacuole formation in cultured retinal cells, and that the addi...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.taap.2008.11.006

    authors： Chung H,Yoon YH,Hwang JJ,Cho KS,Koh JY,Kim JG

    更新日期：2009-03-01 00:00:00

  • Induction of Fas receptor and Fas ligand by nodularin is mediated by NF-κB in HepG2 cells.

    abstract：:Nodularin is a natural toxin with multiple features, including inhibitor of protein phosphatases 1 and 2A as well as tumor initiator and promoter. One unique feature of nodularin is that this chemical is a hepatotoxin. It can accumulate into the liver after contact and lead to severe damage to hepatocyte, such as apop...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.taap.2011.01.009

    authors： Feng G,Li Y,Bai Y

    更新日期：2011-03-15 00:00:00

  • Inhibition of Fas receptor (CD95)-induced hepatic caspase activation and apoptosis by acetaminophen in mice.

    abstract：:The mechanism of liver cell injury induced by an overdose of the analgesic acetaminophen (AAP) remains controversial. Recently, it was hypothesized that a significant number of hepatocytes die by apoptosis. Since caspases have been implicated as critical signal and effector proteases in apoptosis, we investigated thei...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1006/taap.1999.8635

    authors： Lawson JA,Fisher MA,Simmons CA,Farhood A,Jaeschke H

    更新日期：1999-05-01 00:00:00

  • The hematotoxic effects of 6-hydroxy-trans,trans-2,4-hexadienal, a reactive metabolite of trans,trans-muconaldehyde, in CD-1 mice.

    abstract：:6-Hydroxy-trans,trans-2,4-hexadienal (CHO-M-OH) is a metabolite of trans,trans-muconaldehyde (muconaldehyde or MUC), a microsomal hematotoxic ring-opened metabolite of benzene. In the present study, the toxicity of CHO-M-OH was examined. In order to assess potential toxic effects of CHO-M-OH on the maturation of eryth...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1006/taap.1995.1101

    authors： Zhang Z,Schafer F,Schoenfeld H,Cooper K,Snyder R,Goldstein BD,Witz G

    更新日期：1995-06-01 00:00:00

  • Mechanistic studies of in vitro cytotoxicity of poly(amidoamine) dendrimers in mammalian cells.

    abstract：:Poly(amidoamine) (PAMAM) dendrimer nanoparticles have been demonstrated to elicit a well defined cytotoxicological response from mammalian cell lines, the response increasing systematically with dendrimer generation and number of surface amino groups. In this work, using generation G4, G5, and G6 dendrimers, this syst...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.taap.2010.08.016

    authors： Mukherjee SP,Lyng FM,Garcia A,Davoren M,Byrne HJ

    更新日期：2010-11-01 00:00:00

  • Myelopotentiating effect of curcumin in tumor-bearing host: role of bone marrow resident macrophages.

    abstract：:The present investigation was undertaken to study if curcumin, which is recognized for its potential as an antineoplastic and immunopotentiating agent, can also influence the process of myelopoiesis in a tumor-bearing host. Administration of curcumin to tumor-bearing host augmented count of bone marrow cell (BMC) acco...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.taap.2012.06.004

    authors： Vishvakarma NK,Kumar A,Kumar A,Kant S,Bharti AC,Singh SM

    更新日期：2012-08-15 00:00:00

  • How do male germ cells handle DNA damage?

    abstract：:Male reproductive health has received considerable attention in recent years. In addition to declining sperm quality, fertility problems and increased incidence of testicular cancer, there is accumulating evidence that genetic damage, in the form of unrepaired DNA lesions or de novo mutations, may be transmitted via s...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章,评审

    doi：10.1016/j.taap.2005.01.060

    authors： Olsen AK,Lindeman B,Wiger R,Duale N,Brunborg G

    更新日期：2005-09-01 00:00:00

  • Analysis of the safety and pharmacodynamics of human fibrinogen concentrate in animals.

    abstract：:Fibrinogen, a soluble 340kDa plasma glycoprotein, is critical in achieving and maintaining hemostasis. Reduced fibrinogen levels are associated with an increased risk of bleeding and recent research has investigated the efficacy of fibrinogen concentrate for controlling perioperative bleeding. European guidelines on t...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.taap.2014.07.019

    authors： Beyerle A,Nolte MW,Solomon C,Herzog E,Dickneite G

    更新日期：2014-10-01 00:00:00