当前位置： SCI文献检索 > TOXICOLOGY AND APPLIED PHARMACOLOGY期刊下所有文献 > Protection of the Cyp1a2(-/-) null mouse against uroporphyria and hepatic injury following exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

Protection of the Cyp1a2(-/-) null mouse against uroporphyria and hepatic injury following exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

Abstract：

:The effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the liver of C57BL/6J mice is a model for clinical sporadic porphyria cutanea tarda (PCT). There is massive uroporphyria, inhibition of uroporphyrinogen decarboxylase (UROD) activity, and hepatocellular damage. A variety of evidence implicates the CYP1A2 enzyme as necessary for mouse uroporphyria. Here we report that, 5 weeks after a single oral dose of TCDD (75 microg/kg), Cyp1a2(+/+) wild-type mice showed severe uroporphyria and greater than 90% decreases in UROD activity; in contrast, despite exposure to this potent agent Cyp1a2(-/-) knockout mice displayed absolutely no increases in hepatic porphyrin levels, even after prior iron overload, and no detectable inhibition of UROD activity. Plasma levels of alanine-aminotransferase (ALT) and aspartate aminotransferase (AST)-although elevated in both genotypes after TCDD exposure-were significantly less in Cyp1a2(-/-) than in Cyp1a2(+/+) mice, suggesting that the absence of CYP1A2 also affords partial protection against TCDD-induced liver toxicity. Histological examination confirmed a decrease in hepatocellular damage in TCDD-treated Cyp1a2(-/-) mice; in particular, there was no bile duct damage or proliferation that in the Cyp1a2(+/+) mice might be caused by uroporphyrin. We conclude that CYP1A2 is both necessary and essential for the potent uroporphyrinogenic effects of TCDD in mice, and that CYP1A2 also plays a role in contributing to TCDD-induced hepatocellular injury. This study has implications for both the toxicity assessment of TCDD and the hepatic injury seen in PCT patients.

journal_name

Toxicol Appl Pharmacol

journal_title

Toxicology and applied pharmacology

authors

Smith AG,Clothier B,Carthew P,Childs NL,Sinclair PR,Nebert DW,Dalton TP

doi

10.1006/taap.2001.9167

subject

Has Abstract

pub_date

2001-06-01 00:00:00

pages

89-98

issue

2

eissn

0041-008X

issn

1096-0333

pii

S0041-008X(01)99167-7

journal_volume

173

pub_type

杂志文章

相关文献

TOXICOLOGY AND APPLIED PHARMACOLOGY文献大全
  • Response of mouse skin to tattooing: use of SKH-1 mice as a surrogate model for human tattooing.

    abstract：:Tattooing is a popular cosmetic practice involving more than 45 million US citizens. Since the toxicology of tattoo inks and pigments used to formulate tattoo inks has not been reported, we studied the immunological impact of tattooing and determined recovery time from this trauma. SKH-1 hairless mice were tattooed us...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.taap.2005.04.003

    authors： Gopee NV,Cui Y,Olson G,Warbritton AR,Miller BJ,Couch LH,Wamer WG,Howard PC

    更新日期：2005-12-01 00:00:00

  • The surface charge of visible particulate matter predicts biological activation in human bronchial epithelial cells.

    abstract：:The physicochemical complexity of airborne particulate matter (PM) has hampered identifying a specific mechanism(s) for its toxicity. In this study, selected physicochemical characteristics (i.e., size, particle number, acidity, and surface charge) were measured on various field PM, derived from urban ambient (St. Lou...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1006/taap.2001.9341

    authors： Veronesi B,de Haar C,Lee L,Oortgiesen M

    更新日期：2002-02-01 00:00:00

  • The effects of organophosphate-induced cholinergic stimulation on the antibody response to sheep erythrocytes in inbred mice.

    abstract：:In a previous study, we demonstrated that parathion suppressed both the primary IgM and IgG response to sheep erythrocytes (SRC) in inbred and outbred mice (G. P. Casale, S. D. Cohen, and R. A. DiCapua, 1982, toxicologist 2, 94). Suppression occurred after a dosage which produced cholinergic effects but was absent aft...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1016/0041-008x(83)90004-2

    authors： Casale GP,Cohen SD,DiCapua RA

    更新日期：1983-04-01 00:00:00

  • Herb-drug interaction prediction based on the high specific inhibition of andrographolide derivatives towards UDP-glucuronosyltransferase (UGT) 2B7.

    abstract：:Herb-drug interaction strongly limits the clinical application of herbs and drugs, and the inhibition of herbal components towards important drug-metabolizing enzymes (DMEs) has been regarded as one of the most important reasons. The present study aims to investigate the inhibition potential of andrographolide derivat...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.taap.2014.02.021

    authors： Ma HY,Sun DX,Cao YF,Ai CZ,Qu YQ,Hu CM,Jiang C,Dong PP,Sun XY,Hong M,Tanaka N,Gonzalez FJ,Ma XC,Fang ZZ

    更新日期：2014-05-15 00:00:00

  • Sarin-like and soman-like organophosphorous agents activate PLCgamma in rat brains.

    abstract：:We report that there is a time-related change in the phospholipase C (PLC) activities of rat brain cytosol and membrane fractions after iv injection of a soman-like or a sarin-like organophosphorous agent (bis(isopropyl methyl)phosphonate [BIMP] and bis(pinacolyl methyl)phosphonate [BPMP]). PLCgamma was activated in t...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1006/taap.1998.8628

    authors： Niijima H,Nagao M,Nakajima M,Takatori T,Matsuda Y,Iwase H,Kobayashi M

    更新日期：1999-04-01 00:00:00

  • Development and validation of an alternative dermal sensitization test: the mouse ear swelling test (MEST).

    abstract：:Traditional predictive tests for dermal sensitization in humans use the albino guinea pig as a model. A number of factors make the prospect of an alternative attractive. Guinea pig designs are labor intensive, require significant animal, caging, and husbandry resources, and are expensive. Extensive development and val...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1016/0041-008x(86)90419-9

    authors： Gad SC,Dunn BJ,Dobbs DW,Reilly C,Walsh RD

    更新日期：1986-06-15 00:00:00

  • Thiopurine-induced toxicity is associated with dysfunction variant of the human molybdenum cofactor sulfurase gene (xanthinuria type II).

    abstract：BACKGROUND:The aim of our study was to identify the genetic background of thiopurine-induced toxicity in a patient with a wild-type thiopurine methyltransferase genotype and activity. A 38-year-old Caucasian woman presented with cutaneous necrotizing vasculitis pancytopenia one month after starting azathioprine therapy...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.taap.2018.06.015

    authors： Stiburkova B,Pavelcova K,Petru L,Krijt J

    更新日期：2018-08-15 00:00:00

  • Area under the curve as a dose metric for promotional responses following 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure.

    abstract：:An underlying basis of risk assessment is that an equivalent risk for a specified dose metric exists that allows for extrapolation of dose-response relationships between species. To better understand the use of area under the curve (AUC) as a dose metric for complex biological responses following 2,3,7,8-tetrachlorodi...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1016/s0041-008x(03)00225-4

    authors： Kim AH,Kohn MC,Nyska A,Walker NJ

    更新日期：2003-08-15 00:00:00

  • Prevention of short-term ultraviolet B radiation-mediated damages by resveratrol in SKH-1 hairless mice.

    abstract：:Nonmelanoma skin cancer is the most common cancer among humans and solar UV radiation, particularly its UVB component (290-320 nm), is its major cause. One way to reduce the occurrence of the cancer is via the use of substances (often antioxidants) termed "photochemopreventive agents". Resveratrol (trans-3,4',5-trihyd...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1016/s0041-008x(02)00014-5

    authors： Afaq F,Adhami VM,Ahmad N

    更新日期：2003-01-01 00:00:00

  • The kinetics of intravenously administered methyl mercury in man.

    abstract：:We describe a compartmental pharmacokinetic model for methyl mercury and its metabolite mercuric mercury in humans. A tracer dose of 203Hg-labeled methyl mercury was administered iv to seven healthy young adult male volunteers. Blood samples were obtained periodically and urine and feces were collected throughout the ...

    journal_title：Toxicology and applied pharmacology

    pub_type： 临床试验,杂志文章

    doi：10.1006/taap.1994.1204

    authors： Smith JC,Allen PV,Turner MD,Most B,Fisher HL,Hall LL

    更新日期：1994-10-01 00:00:00

  • Blood pressure elevation in young dogs during low-level lead poisoning.

    abstract：:Clinical and experimental studies suggest an association between low-level lead exposure and hypertension. This association was investigated in six 3-month-old dogs who were randomly paired with their littermates. The daily oral dose of lead acetate was 1.0 mg Pb/kg body wt for 5 months; the controls received equimola...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1016/0041-008x(88)90041-5

    authors： Fine BP,Vetrano T,Skurnick J,Ty A

    更新日期：1988-05-01 00:00:00

  • Electrophysiological effects of desmethylimipramine and desmethyldoxepin on canine cardiac Purkinje fibers.

    abstract：:Although the tricyclic antidepressant drugs imipramine and doxepin exert similar direct electrophysiological effects on cardiac cells, toxic cardiac arrhythmias and conduction disturbances are much more commonly associated with imipramine than doxepin in clinical use. To ascertain if this discrepancy could be due to d...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1016/0041-008x(84)90143-1

    authors： Brennan FJ

    更新日期：1984-06-30 00:00:00

  • Dendritic cells and skin sensitization: biological roles and uses in hazard identification.

    abstract：:Recent advances have been made in our understanding of the roles played by cutaneous dendritic cells (DCs) in the induction of contact allergy. A number of associated changes in epidermal Langerhans cell phenotype and function required for effective skin sensitization are providing the foundations for the development ...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章,评审

    doi：10.1016/j.taap.2007.03.006

    authors： Ryan CA,Kimber I,Basketter DA,Pallardy M,Gildea LA,Gerberick GF

    更新日期：2007-06-15 00:00:00

  • Polycyclic aromatic hydrocarbons as skin carcinogens: comparison of benzo[a]pyrene, dibenzo[def,p]chrysene and three environmental mixtures in the FVB/N mouse.

    abstract：:The polycyclic aromatic hydrocarbon (PAH), benzo[a]pyrene (BaP), was compared to dibenzo[def,p]chrysene (DBC) and combinations of three environmental PAH mixtures (coal tar, diesel particulate and cigarette smoke condensate) using a two stage, FVB/N mouse skin tumor model. DBC (4nmol) was most potent, reaching 100% tu...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.taap.2012.08.014

    authors： Siddens LK,Larkin A,Krueger SK,Bradfield CA,Waters KM,Tilton SC,Pereira CB,Löhr CV,Arlt VM,Phillips DH,Williams DE,Baird WM

    更新日期：2012-11-01 00:00:00

  • Ellagic acid protects endothelial cells from oxidized low-density lipoprotein-induced apoptosis by modulating the PI3K/Akt/eNOS pathway.

    abstract：:Endothelial apoptosis is a driving force in atherosclerosis development. Oxidized low-density lipoprotein (oxLDL) promotes inflammatory and thrombotic processes and is highly atherogenic, as it stimulates macrophage cholesterol accumulation and foam cell formation. Previous studies have shown that the phosphatidylinos...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.taap.2010.07.025

    authors： Ou HC,Lee WJ,Lee SD,Huang CY,Chiu TH,Tsai KL,Hsu WC,Sheu WH

    更新日期：2010-10-15 00:00:00

  • Proteomic profiling revealed the functional networks associated with mitotic catastrophe of HepG2 hepatoma cells induced by 6-bromine-5-hydroxy-4-methoxybenzaldehyde.

    abstract：:Mitotic catastrophe, a form of cell death resulting from abnormal mitosis, is a cytotoxic death pathway as well as an appealing mechanistic strategy for the development of anti-cancer drugs. In this study, 6-bromine-5-hydroxy-4-methoxybenzaldehyde was demonstrated to induce DNA double-strand break, multipolar spindles...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.taap.2011.03.003

    authors： Zhang B,Huang B,Guan H,Zhang SM,Xu QZ,He XP,Liu XD,Wang Y,Shang ZF,Zhou PK

    更新日期：2011-05-01 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

  • Concentration-response relationships of rat lungs to exposure to oxidant air pollutants: a critical test of Haber's Law for ozone and nitrogen dioxide.

    abstract：:Exposure protocols were designed to ask whether lung damage in rats exposed to either ozone or nitrogen dioxide is proportional to dose rate or to cumulative dose. Thus, the response of rats to a constant product of concentration of oxidant air pollutant and time of exposure (C x T) was evaluated for 3-day exposures o...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1016/0041-008x(92)90281-v

    authors： Gelzleichter TR,Witschi H,Last JA

    更新日期：1992-01-01 00:00:00

  • The NADPH oxidase inhibitor apocynin (acetovanillone) induces oxidative stress.

    abstract：:Apocynin (acetovanillone) is often used as a specific inhibitor of NADPH oxidase. In N11 glial cells, apocynin induced, in a dose-dependent way, a significant increase of both malonyldialdehyde level (index of lipid peroxidation) and lactate dehydrogenase release (index of a cytotoxic effect). Apocynin evoked also, in...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.taap.2005.07.011

    authors： Riganti C,Costamagna C,Bosia A,Ghigo D

    更新日期：2006-05-01 00:00:00

  • The area under the concentration-time curve of all-trans-retinoic acid is the most suitable pharmacokinetic correlate to the embryotoxicity of this retinoid in the rat.

    abstract：:Earlier studies with etretinate and its metabolite acitretin suggested that area under the concentration-time curve (AUC) is the most suitable pharmacokinetic correlate to etretinate-induced teratogenesis. In an attempt to test this hypothesis with respect to the embryotoxic effects of all-trans-retinoic acid (all-tra...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1006/taap.1997.8105

    authors： Tzimas G,Thiel R,Chahoud I,Nau H

    更新日期：1997-04-01 00:00:00

  • The activity of membrane enzymes in homogenate fractions of rat kidney after administration of lead.

    abstract：:Rats received one or two consecutive daily ip injections, each 0.5 mg Pb2+/100 g body weight, and the kidneys were studied 48 or 24 hr, respectively, after the injection. Renal brush border preparations from Pb2+-treated rats exhibited significant decreases in the activity of alanine aminopeptidase and gamma-glutamyl ...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1016/0041-008x(83)90224-7

    authors： Nicholls DM,Teichert-Kuliszewska K,Kuliszewski MJ

    更新日期：1983-02-01 00:00:00

  • A low-molecular-weight cadmium-binding substance in human and rat livers and human blood.

    abstract：:A cadmium-binding substance with a molecular weight even lower than that of metallothionein was demonstrated on Sephadex G-75 gel filtration chromatography of the soluble fractions from newborn human and adult rat liver homogenates and adult human hemolysate which were mixed with CdCl2 in vitro. This substance was pur...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1016/0041-008x(84)90057-7

    authors： Katoh M,Mizutani N,Keino H,Kashiwamata S

    更新日期：1984-03-30 00:00:00

  • Role of surfactant protein-A (SP-A) in lung injury in response to acute ozone exposure of SP-A deficient mice.

    abstract：:Millions are exposed to ozone levels above recommended limits, impairing lung function, causing epithelial damage and inflammation, and predisposing some individuals to pneumonia, asthma, and other lung conditions. Surfactant protein-A (SP-A) plays a role in host defense, the regulation of inflammation, and repair of ...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.taap.2006.12.017

    authors： Haque R,Umstead TM,Ponnuru P,Guo X,Hawgood S,Phelps DS,Floros J

    更新日期：2007-04-01 00:00:00

  • Dantrolene and mepacrine antagonize the hemolysis of human red blood cells by halothane and bee venom phospholipase A2.

    abstract：:Dantrolene is an effective antagonist of anesthesia-induced malignant hyperthermia due to a poorly understood action on skeletal muscle. The present study examines whether the red blood cell can be used as a model to investigate the mechanism of dantrolene action. Halothane (4.7 mM) caused 9% hemolysis of red blood ce...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1016/0041-008x(87)90133-5

    authors： Fletcher JE,Kistler P,Rosenberg H,Michaux K

    更新日期：1987-09-30 00:00:00

  • Exposure to bisphenol A in young adult mice does not alter ovulation but does alter the fertilization ability of oocytes.

    abstract：:Follicle growth culminates in ovulation, which allows for the expulsion of fertilizable oocytes and the formation of corpora lutea. Bisphenol A (BPA) is present in many consumer products, and it has been suggested that BPA impairs ovulation; however, the underlying mechanisms are unknown. Therefore, this study first e...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.taap.2015.10.010

    authors： Moore-Ambriz TR,Acuña-Hernández DG,Ramos-Robles B,Sánchez-Gutiérrez M,Santacruz-Márquez R,Sierra-Santoyo A,Piña-Guzmán B,Shibayama M,Hernández-Ochoa I

    更新日期：2015-12-15 00:00:00

  • Comparative aromatic hydroxylation and N-demethylation of MPTP neurotoxin and its analogs, N-methylated beta-carboline and isoquinoline alkaloids, by human cytochrome P450 2D6.

    abstract：:1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxin is a chemical inducer of Parkinson's disease (PD) whereas N-methylated beta-carbolines and isoquinolines are naturally occurring analogues of MPTP involved in PD. This research has studied the oxidation of MPTP by human CYP2D6 (CYP2D6*1 and CYP2D6*10 allel...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.taap.2006.06.003

    authors： Herraiz T,Guillén H,Arán VJ,Idle JR,Gonzalez FJ

    更新日期：2006-11-01 00:00:00

  • Effect of sulfhydryl-deficient diets on hepatic metallothionein, glutathione, and adenosine 3'-phosphate 5'-phosphosulfate (PAPS) levels in rats.

    abstract：:Low dietary concentrations of methionine and cysteine are known to decrease hepatic glutathione content. However, it is not known if restricting the dietary content of these sulfur containing amino acids also affects hepatic levels of adenosine 3'-phosphate 5'-phosphosulfate (PAPS), the cofactor for sulfation, or meta...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1016/0041-008x(90)90025-p

    authors： Sendelbach LE,White CA,Howell S,Gregus Z,Klaassen CD

    更新日期：1990-02-01 00:00:00

  • Maternal selenium deficiency enhances the fetolethal toxicity of methyl mercury.

    abstract：:The effect of maternal selenium deficiency on methyl mercury fetotoxicity was examined in the ICR strain of mice. Pregnant mice were fed either selenium-deficient diets based on torula yeast or selenium-supplemented diets which were identical to the former except that 0.1, 0.2, or 0.4 mg of selenium per kilogram of di...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1016/0041-008x(87)90207-9

    authors： Nishikido N,Furuyashiki K,Naganuma A,Suzuki T,Imura N

    更新日期：1987-05-01 00:00:00

  • Ondansetron can enhance cisplatin-induced nephrotoxicity via inhibition of multiple toxin and extrusion proteins (MATEs).

    abstract：:The nephrotoxicity limits the clinical application of cisplatin. Human organic cation transporter 2 (OCT2) and multidrug and toxin extrusion proteins (MATEs) work in concert in the elimination of cationic drugs such as cisplatin from the kidney. We hypothesized that co-administration of ondansetron would have an effec...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.taap.2013.08.024

    authors： Li Q,Guo D,Dong Z,Zhang W,Zhang L,Huang SM,Polli JE,Shu Y

    更新日期：2013-11-15 00:00:00

  • Valproate induced hepatic steatosis by enhanced fatty acid uptake and triglyceride synthesis.

    abstract：:Steatosis is the characteristic type of VPA-induced hepatotoxicity and may result in life-threatening hepatic lesion. Approximately 61% of patients treated with VPA have been diagnosed with hepatic steatosis through ultrasound examination. However, the mechanisms underlying VPA-induced intracellular fat accumulation a...

    journal_title：Toxicology and applied pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.taap.2017.03.022

    authors： Bai X,Hong W,Cai P,Chen Y,Xu C,Cao D,Yu W,Zhao Z,Huang M,Jin J

    更新日期：2017-06-01 00:00:00