Isothiocyanates reduce mercury accumulation via an Nrf2-dependent mechanism during exposure of mice to methylmercury.

Abstract:

BACKGROUND:Methylmercury (MeHg) exhibits neurotoxicity through accumulation in the brain. The transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2) plays an important role in reducing the cellular accumulation of MeHg. OBJECTIVES:We investigated the protective effect of isothiocyanates, which are known to activate Nrf2, on the accumulation of mercury after exposure to MeHg in vitro and in vivo. METHODS:We used primary mouse hepatocytes in in vitro experiments and mice as an in vivo model. We used Western blotting, luciferase assays, atomic absorption spectrometry assays, and MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assays, and we identified toxicity in mice based on hind-limb flaccidity and mortality. RESULTS:The isothiocyanates 6-methylsulfinylhexyl isothiocyanate (6-HITC) and sulforaphane (SFN) activated Nrf2 and up-regulated downstream proteins associated with MeHg excretion, such as glutamate-cysteine ligase, glutathione S-transferase, and multidrug resistance-associated protein, in primary mouse hepatocytes. Under these conditions, intracellular glutathione levels increased in wild-type but not Nrf2-deficient primary mouse hepatocytes. Pretreatment with 6-HITC and SFN before MeHg exposure suppressed cellular accumulation of mercury and cytotoxicity in wild-type but not Nrf2-deficient primary mouse hepatocytes. In comparison, in vivo administration of MeHg to Nrf2-deficient mice resulted in increased sensitivity to mercury concomitant with an increase in mercury accumulation in the brain and liver. Injection of SFN before administration of MeHg resulted in a decrease in mercury accumulation in the brain and liver of wild-type, but not Nrf2-deficient, mice. CONCLUSIONS:Through activation of Nrf2, 6-HITC and SFN can suppress mercury accumulation and intoxication caused by MeHg intake.

authors

Toyama T,Shinkai Y,Yasutake A,Uchida K,Yamamoto M,Kumagai Y

doi

10.1289/ehp.1003123

subject

Has Abstract

pub_date

2011-08-01 00:00:00

pages

1117-22

issue

8

eissn

0091-6765

issn

1552-9924

journal_volume

119

pub_type

杂志文章
  • Benzene adducts with rat nucleic acids and proteins: dose-response relationship after treatment in vivo.

    abstract::The dose-response relationship of the benzene covalent interaction with biological macromolecules from rat organs was studied. The administered dose range was 3.6 x 10(7) starting from the highest dosage employed, 486 mg/kg, which is oncogenic for rodents, and included low and very low dosages. The present study was i...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.8982259

    authors: Mazzullo M,Bartoli S,Bonora B,Colacci A,Grilli S,Lattanzi G,Niero A,Turina MP,Parodi S

    更新日期:1989-07-01 00:00:00

  • Endocrine disruptors and human health--is there a problem? An update.

    abstract::It has been hypothesized that environmental exposure to synthetic estrogenic chemicals and related endocrine-active compounds may be responsible for a global decrease in sperm counts, decreased male reproductive capacity, and breast cancer in women. Results of recent studies show that there are large demographic varia...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章,评审

    doi:10.1289/ehp.00108487

    authors: Safe SH

    更新日期:2000-06-01 00:00:00

  • Pulmonary toxicity of bleomycin.

    abstract::Diffuse pulmonary fibrosis is associated with bleomycin administration to humans. The sequential reactions of lung cells to this drug have now been investigated in mice following injection of 20 mg/kg bleomycin twice per week for 4 to 8 weeks. Cytoplasmic and subendothelial edema was first observed in large vessels an...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.7616119

    authors: Adamson IY

    更新日期:1976-08-01 00:00:00

  • State-of-the-science workshop report: issues and approaches in low-dose-response extrapolation for environmental health risk assessment.

    abstract::Low-dose extrapolation model selection for evaluating the health effects of environmental pollutants is a key component of the risk assessment process. At a workshop held in Baltimore, Maryland, on 23-24 April 2007, sponsored by U.S. Environmental Protection Agency and Johns Hopkins Risk Sciences and Public Policy Ins...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.11502

    authors: White RH,Cote I,Zeise L,Fox M,Dominici F,Burke TA,White PD,Hattis DB,Samet JM

    更新日期:2009-02-01 00:00:00

  • Nutritional needs in environmental intoxication: vitamin E and air pollution, an example.

    abstract::Dietary vitamin E affects the susceptibility of mice and rats to ozone and nitrogen dioxide, suggesting a free radical mechanism of toxicity. Conventional peroxidation does not completely explain the effects of alterations of lung fatty acid composition on both nitrogen dioxide and ozone toxicity. A new scheme is prop...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.7929105

    authors: Menzel DB

    更新日期:1979-04-01 00:00:00

  • Coupling between annual and ENSO timescales in the malaria-climate association in Colombia.

    abstract::We present evidence that the El Niño phenomenon intensifies the annual cycle of malaria cases for Plasmodium vivax and Plasmodium falciparum in endemic areas of Colombia as a consequence of concomitant anomalies in the normal annual cycle of temperature and precipitation. We used simultaneous analyses of both variable...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.01109489

    authors: Poveda G,Rojas W,Quiñones ML,Vélez ID,Mantilla RI,Ruiz D,Zuluaga JS,Rua GL

    更新日期:2001-05-01 00:00:00

  • Developmental neurotoxicity of chlorpyrifos: what is the vulnerable period?

    abstract::Previously, we found that exposure of neonatal rats to chlorpyrifos (CPF) produced brain cell damage and loss, with resultant abnormalities of synaptic development. We used the same biomarkers to examine prenatal CPF treatment so as to define the critical period of vulnerability. One group of pregnant rats received CP...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.021101097

    authors: Qiao D,Seidler FJ,Padilla S,Slotkin TA

    更新日期:2002-11-01 00:00:00

  • Effect of air pollution on daily mortality in Hong Kong.

    abstract::In different weather conditions, constituents and concentrations of pollutants, personal exposure, and biologic responses to air pollution may vary. In this study we assessed the effects of four air pollutants on mortality in both cool and warm seasons in Hong Kong, a subtropical city. Daily counts of mortality, due t...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.01109335

    authors: Wong CM,Ma S,Hedley AJ,Lam TH

    更新日期:2001-04-01 00:00:00

  • Using the micronucleus assay to detect genotoxic effects of metal ions.

    abstract::The lymphocyte micronucleus assay was used to measure the average frequency of micronuclei in a population and thus assess genotoxic effects. Data from 174 persons give an average value of 16.4 +/- 7.3, and a slight age-dependence was observed. To detect combined environmental mutagen injuries the micronucleus assay w...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.101-1521140

    authors: Bérces J,Otos M,Szirmai S,Crane-Uruena C,Köteles GJ

    更新日期:1993-10-01 00:00:00

  • Methylmercury exposure and adverse cardiovascular effects in Faroese whaling men.

    abstract:BACKGROUND:Methylmercury (MeHg), a worldwide contaminant found in fish and seafood, has been linked to an increased risk of cardiovascular mortality. OBJECTIVE:We examined 42 Faroese whaling men (30-70 years of age) to assess possible adverse effects within a wide range of MeHg exposures from consumption of pilot whal...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.11608

    authors: Choi AL,Weihe P,Budtz-Jørgensen E,Jørgensen PJ,Salonen JT,Tuomainen TP,Murata K,Nielsen HP,Petersen MS,Askham J,Grandjean P

    更新日期:2009-03-01 00:00:00

  • UV-B exposure impairs resistance to infection by Trichinella spiralis.

    abstract::To assess the possibility that increases in UV-B exposure on the earth's surface could lead to impaired resistance to several infectious diseases, we studied the effect of UV-B exposure on resistance against Trichinella spiralis. Wistar rats, orally infected with T. spiralis larvae, were exposed to suberythemal doses ...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.94102298

    authors: Goettsch W,Garssen J,Deijns A,de Gruijl FR,van Loveren H

    更新日期:1994-03-01 00:00:00

  • Application of HPLC to the isolation of molecular targets in dosimetry studies.

    abstract::High-performance liquid chromatography (HPLC) methods are described which permit the rapid isolation of multiple target macromolecules from the tissues of animals exposed to chemical mutagens. DNA and selected chromosomal proteins are isolated in a simple two step separation scheme. Isolated nuclei are dissolved in 3 ...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.856273

    authors: Balhorn R,Mazrimas JA,Corzett M

    更新日期:1985-10-01 00:00:00

  • Distribution of metallothionein-bound cadmium and cadmium chloride in mice: preliminary studies.

    abstract::Metallothionein from livers of mice was isolated by gel chromatography and isoelectric focusing. One of two forms thus obtained contained 32 percent cysteine. This form, labeled in vitro with 109Cd, was injected intravenously in mice, and the distribution of 109Cd was studied. Animals killed after 4 hrs had over 80 pe...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.7512103

    authors: Nordberg M,Nordberg GF

    更新日期:1975-12-01 00:00:00

  • Effects of noise and electromagnetic fields on reproductive outcomes.

    abstract::Much public health research has been directed to studies of cancer risks due to chemical agents. Recently, increasing attention has been given to adverse reproductive outcomes as another, shorter-term biologic indicator of public health impact. Further, several low-level ubiquitous physical agents have been implicated...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章,评审

    doi:10.1289/ehp.8981193

    authors: Meyer RE,Aldrich TE,Easterly CE

    更新日期:1989-05-01 00:00:00

  • Effects of chronic arsenic exposure on hematopoietic function in adult mammalian liver.

    abstract::In these studies the effects of ingested arsenic (As(+5)) on hepatic heme biosynthetic capability and hemoprotein function in adult male rats were investigated. Animals exposed for 6 weeks to 0, 20, 40, or 85 ppm sodium arsenate in the drinking water suffered depression of hepatic delta-aminolevulinic acid (ALA) synth...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.7719209

    authors: Woods JS,Fowler BA

    更新日期:1977-08-01 00:00:00

  • Neighborhood food environment and walkability predict obesity in New York City.

    abstract:BACKGROUND:Differences in the neighborhood food environment may contribute to disparities in obesity. OBJECTIVES:The purpose of this study was to examine the association of neighborhood food environments with body mass index (BMI) and obesity after control for neighborhood walkability. METHODS:This study employed a c...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.11590

    authors: Rundle A,Neckerman KM,Freeman L,Lovasi GS,Purciel M,Quinn J,Richards C,Sircar N,Weiss C

    更新日期:2009-03-01 00:00:00

  • Medications as a source of human exposure to phthalates.

    abstract::Phthalates are a group of multifunctional chemicals used in consumer and personal care products, plastics, and medical devices. Laboratory studies show that some phthalates are reproductive and developmental toxicants. Recently, human studies have shown measurable levels of several phthalates in most of the U.S. gener...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.6804

    authors: Hauser R,Duty S,Godfrey-Bailey L,Calafat AM

    更新日期:2004-05-01 00:00:00

  • Modification of the interleukin-6 response to air pollution by interleukin-6 and fibrinogen polymorphisms.

    abstract:BACKGROUND:Evidence suggests that cardiovascular effects of air pollution are mediated by inflammation and that air pollution can induce genetic expression of the interleukin-6 gene (IL6). OBJECTIVES:We investigated whether IL6 and fibrinogen gene variants can affect plasma IL-6 responses to air pollution in patients ...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.0800370

    authors: Ljungman P,Bellander T,Schneider A,Breitner S,Forastiere F,Hampel R,Illig T,Jacquemin B,Katsouyanni K,von Klot S,Koenig W,Lanki T,Nyberg F,Pekkanen J,Pistelli R,Pitsavos C,Rosenqvist M,Sunyer J,Peters A

    更新日期:2009-09-01 00:00:00

  • Analysis of dietary intake of selected metals in the NHEXAS-Maryland investigation.

    abstract::As part of a large pilot investigation of multimedia exposure to several classes of environmental contaminants, the National Human Exposure Assessment Survey (NHEXAS)-Maryland study, we collected 388 semiquantitative food checklists and duplicate diet solid food samples, analyzed for arsenic, cadmium, chromium, and le...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.01109121

    authors: Ryan PB,Scanlon KA,MacIntosh DL

    更新日期:2001-02-01 00:00:00

  • Prenatal Exposure to Perfluoroalkyl Acids and Serum Testosterone Concentrations at 15 Years of Age in Female ALSPAC Study Participants.

    abstract:BACKGROUND:Exposure to perfluorooctane sulfonic acid (PFOS) or to perfluorooctanoic acid (PFOA) increases mouse and human peroxisome proliferator-activated receptor alpha (PPARα) subtype activity, which influences lipid metabolism. Because cholesterol is the substrate from which testosterone is synthesized, exposure to...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.1408847

    authors: Maisonet M,Calafat AM,Marcus M,Jaakkola JJ,Lashen H

    更新日期:2015-12-01 00:00:00

  • Effect of chlorocamphene on the isoenzyme spectrum of lactate dehydrogenase in rat serum and liver.

    abstract::Rats were used to study the general activity and the isoenzyme spectrum of lactate dehydrogenase (LDH) during single-instance and long-term introduction of polychlorocamphene. Total lactate dehydrogenase activity decreases in the liver during the single-instance introduction of half the LD50 (120 mg/kg). The isoenzyme...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.7613127

    authors: Kuz'minskaya UA,Alekhina SM

    更新日期:1976-02-01 00:00:00

  • Risk estimation for badge-monitored radiation workers.

    abstract::In estimating the cancer mortality risk for radiation workers it is conventional to use data obtained from the populations exposed to radiation as a result of the atomic bomb blast in Hiroshima and Nagasaki. This A-bomb experience resulted in relatively high doses of radiation and short periods of exposure. The availa...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.97105s61603

    authors: Stewart A

    更新日期:1997-12-01 00:00:00

  • The privileged access model of 1,3-butadiene disposition.

    abstract::In previous attempts to model disposition of 1,3-butadiene in mice and rats, parameter values for 1,2-epoxybut-3-ene metabolism were optimized to reproduce elimination of this gas from closed chambers. However, each of these models predicted much higher concentrations of circulating epoxybutene than were subsequently ...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.00108s5911

    authors: Kohn MC,Melnick RL

    更新日期:2000-10-01 00:00:00

  • Biostatistical analysis of the micronucleus mutagenicity assay based on the assumption of a mixing distribution.

    abstract::The in vivo micronucleus assay can be analyzed by comparing the number of micronuclei (MN) of several dose groups with those of a control group. In several publications, difficulties arose in estimating a suitable distribution for MN, even in the untreated historical control groups. Mitchell et al. described the prese...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.94102s1121

    authors: Hothorn L

    更新日期:1994-01-01 00:00:00

  • Biomarker measurements in a coastal fish-eating population environmentally exposed to organochlorines.

    abstract::The Lower North Shore region of the St. Lawrence River is home to a fish-eating population that displays an unusually high body burden of several organochlorines, including polychlorinated biphenyls (PCBs) and dioxin-like compounds (DLCs). We measured biomarkers indicative of liver enzyme induction and investigated th...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.7970

    authors: Ayotte P,Dewailly E,Lambert GH,Perkins SL,Poon R,Feeley M,Larochelle C,Pereg D

    更新日期:2005-10-01 00:00:00

  • Reduction in heart rate variability with traffic and air pollution in patients with coronary artery disease.

    abstract:INTRODUCTION:Ambient particulate pollution and traffic have been linked to myocardial infarction and cardiac death risk. Possible mechanisms include autonomic cardiac dysfunction. METHODS:In a repeated-measures study of 46 patients 43-75 years of age, we investigated associations of central-site ambient particulate po...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.0901003

    authors: Zanobetti A,Gold DR,Stone PH,Suh HH,Schwartz J,Coull BA,Speizer FE

    更新日期:2010-03-01 00:00:00

  • Skin permeation and cutaneous hypersensitivity as a basis for making risk assessments of chromium as a soil contaminant.

    abstract::A literature review of experimental and human exposure studies of skin permeation and cutaneous hypersensitivity reactions evoked by chromium was carried out to provide a basis for making a risk assessment of chromium as a soil contaminant. In vitro and in vivo studies demonstrated that 1 to 4% of the applied dose of ...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章,评审

    doi:10.1289/ehp.92-1519389

    authors: Bagdon RE,Hazen RE

    更新日期:1991-05-01 00:00:00

  • Is it worth a dam?

    abstract::Once a sign of modernization and growth, dams are often seen today as symbols of environmental and social devastation. Over 800,000 dams have been built worldwide to provide drinking water, flood control, hydropower, irrigation, navigation, and water storage. Dams do indeed provide these things,but at the cost of seve...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.971051050

    authors: Joyce S

    更新日期:1997-10-01 00:00:00

  • Risk of internal cancers from arsenic in drinking water.

    abstract::The U.S. Environmental Protection Agency is under a congressional mandate to revise its current standard for arsenic in drinking water. We present a risk assessment for cancers of the bladder, liver, and lung from exposure to arsenic in water, based on data from 42 villages in an arseniasis-endemic region of Taiwan. W...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.00108655

    authors: Morales KH,Ryan L,Kuo TL,Wu MM,Chen CJ

    更新日期:2000-07-01 00:00:00

  • Associations between organochlorine contaminant concentrations and clinical health parameters in loggerhead sea turtles from North Carolina, USA.

    abstract::Widespread and persistent organochlorine (OC) contaminants, such as polychlorinated biphenyls (PCBs) and pesticides, are known to have broad-ranging toxicities in wildlife. In this study we investigated, for the first time, their possible health effects on loggerhead sea turtles (Caretta caretta). Nonlethal fat biopsi...

    journal_title:Environmental health perspectives

    pub_type: 杂志文章

    doi:10.1289/ehp.6923

    authors: Keller JM,Kucklick JR,Stamper MA,Harms CA,McClellan-Green PD

    更新日期:2004-07-01 00:00:00