Glutathione Conjugation and Protein Adduction by Environmental Pollutant 2,4-Dichlorophenol In Vitro and In Vivo.

Abstract:

:2,4-Dichlorophenol (2,4-DCP), an environmental pollutant, was reported to cause hepatotoxicity. The biochemical mechanisms of 2,4-DCP induced liver injury remain unknown. The present study showed that 2,4-DCP is chemically reactive and spontaneously reacts with GSH and bovine serum albumin to form GSH conjugates and BSA adducts. The observed conjugation/adduction apparently involved the addition of GSH and departure of chloride via the ipso substitution pathway. Two biliary GSH conjugates and one urinary N-acetyl cysteine conjugate were observed in rats given 2,4-DCP. The N-acetyl cysteine conjugate was chemically synthesized and characterized by mass spectrometry and NMR. As expected, 2,4-DCP was found to modify hepatic protein at cysteine residues in vivo by the same chemistry. The observed protein adduction reached its peak at 15 min and revealed dose dependency. The new findings allowed us to better understand the mechanisms of the toxic action of 2,4-DCP.

journal_name

Chem Res Toxicol

authors

Li Q,Li W,Zhao J,Guo X,Zou Q,Yang Z,Tian R,Peng Y,Zheng J

doi

10.1021/acs.chemrestox.0c00118

subject

Has Abstract

pub_date

2020-09-21 00:00:00

pages

2351-2360

issue

9

eissn

0893-228X

issn

1520-5010

journal_volume

33

pub_type

杂志文章
  • Chemical speciation of trivalent actinides and lanthanides in biological fluids: the dominant in vitro binding form of curium(III) and europium(III) in human urine.

    abstract::Radionuclides represent a serious health risk to humans in the case of incorporation. To elucidate the potential of time-resolved laser-induced fluorescence spectroscopy (TRLFS) to determine the dominant radionuclide species in natural biofluids, we investigated the in vitro speciation of curium(III) in human urine sa...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx100273g

    authors: Heller A,Barkleit A,Bernhard G

    更新日期:2011-02-18 00:00:00

  • Future of toxicology--lipid peroxidation in the future: from biomarker to etiology.

    abstract::On the basis of a large number of reports concerning the detection of lipid peroxidation products as biomarkers in human diseases, there is no doubt that their steady-state levels increase under pathophysiological states associated with oxidative stress. The key question is whether they play any causative roles. This ...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx600304n

    authors: Uchida K

    更新日期:2007-01-01 00:00:00

  • Systematic toxicity mechanism analysis of proton pump inhibitors: an in silico study.

    abstract::Proton pump inhibitors (PPIs) are extensively used for the treatment of gastric acid-related disorders. PPIs appear to be well tolerated and almost have no short-term side effects. However, the clinical adverse reactions of long-term PPI usage are increasingly reported in recent years. So far, there is no study that e...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx5003782

    authors: Wu D,Qiu T,Zhang Q,Kang H,Yuan S,Zhu L,Zhu R

    更新日期:2015-03-16 00:00:00

  • Metabolism of the food-borne mutagen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline in humans.

    abstract::The metabolism of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) was investigated in five human volunteers given a dietary equivalent of 14C-labeled MeIQx. The amount of the dose excreted in urine ranged from 20.2% to 58.6%, with unmetabolized MeIQx accounting for 0.7-2.8% of the dose. Five principal metabolite...

    journal_title:Chemical research in toxicology

    pub_type: 临床试验,杂志文章

    doi:10.1021/tx9701891

    authors: Turesky RJ,Garner RC,Welti DH,Richoz J,Leveson SH,Dingley KH,Turteltaub KW,Fay LB

    更新日期:1998-03-01 00:00:00

  • Formation of glutathionyl-spironolactone disulfide by rat liver cytochromes P450 or hog liver flavin-containing monooxygenases: a functional probe of two-electron oxidations of the thiosteroid?

    abstract::We have previously reported that the diuretic thiosteroid spironolactone (SPL) inactivates rat liver microsomal cytochromes P450 [P450 (P450 3A and P450 2C11)] in a in a mechanism-based fashion, and we have identified two polar SPL metabolites (SPL-sulfinic acid and -sulfonic acid), formed in a partition ratio of appr...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx00024a012

    authors: Decker CJ,Cashman JR,Sugiyama K,Maltby D,Correia MA

    更新日期:1991-11-01 00:00:00

  • Mechanistic Insights into the Cytotoxicity of Graphene Oxide Derivatives in Mammalian Cells.

    abstract::Graphene oxide derivatives (GODs) have superb physical/chemical properties with promise for applications in biomedicine. Shape, size, and chemistry of the GODs are identified as the key parameters that impact any biological system. In this work, the GODs with a wide range of shapes (sheets, helical/longitudinal ribbon...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/acs.chemrestox.9b00391

    authors: Lu P,Zehtab Yazdi A,Han XX,Al Husaini K,Haime J,Waye N,Chen P

    更新日期:2020-09-21 00:00:00

  • Can Galactose Be Converted to Glucose in HepG2 Cells? Improving the in Vitro Mitochondrial Toxicity Assay for the Assessment of Drug Induced Liver Injury.

    abstract::Human hepatocellular carcinoma cells, HepG2, are often used for drug mediated mitochondrial toxicity assessments. Glucose in HepG2 culture media is replaced by galactose to reveal drug-induced mitochondrial toxicity as a marked shift of drug IC50 values for the reduction of cellular ATP. It has been postulated that ga...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/acs.chemrestox.9b00033

    authors: Xu Q,Liu L,Vu H,Kuhls M,Aslamkhan AG,Liaw A,Yu Y,Kaczor A,Ruth M,Wei C,Imredy J,Lebron J,Pearson K,Gonzalez R,Mitra K,Sistare FD

    更新日期:2019-08-19 00:00:00

  • Miscoding by the exocyclic and related DNA adducts 3,N4-etheno-2'-deoxycytidine, 3,N4-ethano-2'-deoxycytidine, and 3-(2-hydroxyethyl)-2'-deoxyuridine.

    abstract::3,N4-Etheno-2'-deoxycytidine, 3-(hydroxyethyl)-2'-deoxyuridine, and 3,N4-ethano-2'-deoxy-cytidine are found in DNA of cells treated with either vinyl chloride or 1,3-bis(2-chloroethyl)-nitrosourea. These exocyclic and related DNA adducts were incorporated into oligodeoxynucleotides, which were then used as templates f...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx00043a021

    authors: Zhang W,Johnson F,Grollman AP,Shibutani S

    更新日期:1995-01-01 00:00:00

  • Enzyme-mediated dialdehyde formation: an alternative pathway for benzo[a]pyrene 7,8-dihydrodiol bioactivation.

    abstract::Polycyclic aromatic hydrocarbons, such as benzo[a]pyrene, are widespread environmental carcinogens of human concern. Several enzymatic systems have been shown to activate benzo[a]pyrene 7, 8-dihydrodiol, the proximate carcinogenic metabolite of benzo[a]pyrene, to a reactive species which produces both a chemiluminesce...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx000159p

    authors: Stansbury KH,Noll DM,Groopman JD,Trush MA

    更新日期:2000-11-01 00:00:00

  • Quantification of N2-carboxymethyl-2'-deoxyguanosine in calf thymus DNA and cultured human kidney epithelial cells by capillary high-performance liquid chromatography-tandem mass spectrometry coupled with stable isotope dilution method.

    abstract::Glyoxal is generated endogenously from the degradation of glucose and the oxidation of carbohydrates, lipids, and the 2-deoxyribose moieties of DNA. Glyoxal is also widely used in industry and is present in cigarette smoke and food. Glyoxal can conjugate with nucleobases and proteins to give advanced glycation end pro...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx900286c

    authors: Wang H,Cao H,Wang Y

    更新日期:2010-01-01 00:00:00

  • Highly Predictive Reprogramming of tRNA Modifications Is Linked to Selective Expression of Codon-Biased Genes.

    abstract::Cells respond to stress by controlling gene expression at several levels, with little known about the role of translation. Here, we demonstrate a coordinated translational stress response system involving stress-specific reprogramming of tRNA wobble modifications that leads to selective translation of codon-biased mRN...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/acs.chemrestox.5b00004

    authors: Chan CT,Deng W,Li F,DeMott MS,Babu IR,Begley TJ,Dedon PC

    更新日期:2015-05-18 00:00:00

  • Comparison of the Base Excision and Direct Reversal Repair Pathways for Correcting 1,N6-Ethenoadenine in Strongly Positioned Nucleosome Core Particles.

    abstract::1,N6-ethenoadenine (εA) is a mutagenic lesion and biomarker observed in numerous cancerous tissues. Two pathways are responsible for its repair: base excision repair (BER) and direct reversal repair (DRR). Alkyladenine DNA glycosylase (AAG) is the primary enzyme that excises εA in BER, generating stable intermediates ...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/acs.chemrestox.0c00089

    authors: Caffrey PJ,Kher R,Bian K,Li D,Delaney S

    更新日期:2020-07-20 00:00:00

  • Comparison of Free Radical Levels in the Aerosol from Conventional Cigarettes, Electronic Cigarettes, and Heat-Not-Burn Tobacco Products.

    abstract::Aerosols from electronic cigarettes and heat-not-burn tobacco products have been found to contain lower levels of almost all compounds from the list of Harmful and Potentially Harmful Constituents known to be present in tobacco products and tobacco smoke than smoke from conventional cigarettes. Free radicals, which al...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/acs.chemrestox.9b00085

    authors: Shein M,Jeschke G

    更新日期:2019-06-17 00:00:00

  • Predicting activation of the promiscuous human pregnane X receptor by pharmacophore ensemble/support vector machine approach.

    abstract::The nuclear receptor human pregnane X receptor (hPXR) is a ligand-regulated transcription factor that responds to a wide range of endogenous and xenobiotic molecules. Upon activation with ligands, hPXR can increase induction levels of metabolic enzymes. Therefore, hPXR plays a critical role in drug metabolism and excr...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx200310j

    authors: Chen CN,Shih YH,Ding YL,Leong MK

    更新日期:2011-10-17 00:00:00

  • Analysis of 4-hydroxy-1-(3-pyridyl)-1-butanone (HPB)-releasing DNA adducts in human exfoliated oral mucosa cells by liquid chromatography-electrospray ionization-tandem mass spectrometry.

    abstract::Quantitation of DNA adducts could provide critical information on the relationship between exposure to tobacco smoke and cancer risk in smokers. In this study, we developed a robust and sensitive liquid chromatography-tandem mass spectrometry method for the analysis of 4-hydroxy-1-(3-pyridyl)-1-butanone (HPB)-releasin...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx300282k

    authors: Stepanov I,Muzic J,Le CT,Sebero E,Villalta P,Ma B,Jensen J,Hatsukami D,Hecht SS

    更新日期:2013-01-18 00:00:00

  • Metabonomic evaluation of Schaedler altered microflora rats.

    abstract::Previously, we identified two distinct metabonomic phenotypes in Sprague-Dawley rats sourced from two different rooms (colonies) in the Charles River, Raleigh facility [Robosky, L. C., Wells, D. F., Egnash, L. A., Manning, M. L., Reily, M. D., and Robertson, D. G. (2005) Metabonomic identification of two distinct phen...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx700184u

    authors: Rohde CM,Wells DF,Robosky LC,Manning ML,Clifford CB,Reily MD,Robertson DG

    更新日期:2007-10-01 00:00:00

  • Enhancement of 2'-deoxyguanosine hydroxylation and DNA damage by coal and oil fly ash in relation to particulate metal content and availability.

    abstract::Epidemiologic studies have shown causal relationships between air pollution particles and adverse health effects in susceptible subpopulations. Fly ash particles (containing water-soluble and insoluble metals) are a component of ambient air particulate pollution and may contribute to particulate-induced health effects...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx000110j

    authors: Prahalad AK,Inmon J,Ghio AJ,Gallagher JE

    更新日期:2000-10-01 00:00:00

  • The inhaled glucocorticoid fluticasone propionate efficiently inactivates cytochrome P450 3A5, a predominant lung P450 enzyme.

    abstract::Inhaled glucocorticoid (GC) therapy is a vital part of the management of chronic asthma. GCs are metabolized by members of the cytochrome P450 3A family in both liver and lung, but the enzymes are differentially expressed. Selective inhibition of one or more P450 3A enzymes could substantially modify target and system...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx100124k

    authors: Murai T,Reilly CA,Ward RM,Yost GS

    更新日期:2010-08-16 00:00:00

  • Metabolism of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline in human hepatocytes: 2-amino-3-methylimidazo[4,5-f]quinoxaline-8-carboxylic acid is a major detoxification pathway catalyzed by cytochrome P450 1A2.

    abstract::Metabolic pathways of the mutagen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) remain incompletely characterized in humans. In this study, the metabolism of MeIQx was investigated in primary human hepatocytes. Six metabolites were characterized by UV and mass spectroscopy. Novel metabolites were additionally ...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx000176e

    authors: Langouët S,Welti DH,Kerriguy N,Fay LB,Huynh-Ba T,Markovic J,Guengerich FP,Guillouzo A,Turesky RJ

    更新日期:2001-02-01 00:00:00

  • Experimental Exposure Assessment of Ionizable Organic Chemicals in In Vitro Cell-Based Bioassays.

    abstract::Exposure assessment in in vitro cell-based bioassays is challenging for ionizable organic chemicals (IOCs), because they are present as more than one chemical species in the bioassay medium. Furthermore, compared to neutral organic chemicals, their binding to medium proteins and lipids is driven by more complex molecu...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/acs.chemrestox.0c00067

    authors: Huchthausen J,Mühlenbrink M,König M,Escher BI,Henneberger L

    更新日期:2020-07-20 00:00:00

  • Immunochemical Detection of Protein Modification Derived from Metabolic Activation of 8-Epidiosbulbin E Acetate.

    abstract::Furanoid 8-epidiosbulbin E acetate (EEA) is one of the most abundant diterpenoid lactones in herbal medicine Dioscorea bulbifera L. (DB). Our early work proved that EEA could be metabolized to EEA-derived cis-enedial (EDE), a reactive intermediate, which is required for the hepatotoxicity observed in experimental anim...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/acs.chemrestox.0c00016

    authors: Zhou S,Zhang N,Hu Z,Lin D,Li W,Peng Y,Zheng J

    更新日期:2020-07-20 00:00:00

  • Synthesis and structural characterization of the N2G-mitomycin C-N2G interstrand cross-link in a model synthetic 23 base pair oligonucleotide DNA duplex.

    abstract::Mitomycin C (MMC) is a genotoxic cancer chemotherapeutic agent that reacts principally at the N2 position of guanine to form one of two predominant monoadducts, or a G-G interstrand cross-link at CpG sites, or a G-G intrastrand cross-link at GpG sites. Previous studies of MMC adduction have principally used very short...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx960070c

    authors: Warren AJ,Hamilton JW

    更新日期:1996-10-01 00:00:00

  • Comparative Toxicogenomic Responses to the Flame Retardant mITP in Developing Zebrafish.

    abstract::Monosubstituted isopropylated triaryl phosphate (mITP) is a major component of Firemaster 550, an additive flame retardant mixture commonly used in polyurethane foams. Developmental toxicity studies in zebrafish established mITP as the most toxic component of FM 550, which causes pericardial edema and heart looping fa...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/acs.chemrestox.6b00423

    authors: Haggard DE,Das SR,Tanguay RL

    更新日期:2017-02-20 00:00:00

  • Metabolism of genistein by rat and human cytochrome P450s.

    abstract::The metabolism of genistein (4',5,7-trihydroxyisoflavone), a phytoestrogen derived from soy products, was investigated using rat and human liver microsomes and recombinant human cytochrome P450 enzymes. Metabolism of genistein by microsomes obtained from rats treated with pyridine, phenobarbital, beta-naphthoflavone, ...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx9802320

    authors: Roberts-Kirchhoff ES,Crowley JR,Hollenberg PF,Kim H

    更新日期:1999-07-01 00:00:00

  • Role of thiocyanate ion in detoxification of the anticancer agent chlorambucil.

    abstract::N,N-Bis(2-chloroethyl)-p-aminophenylbutyric acid (chlorambucil, 1) is an orally administrated drug widely used in the chemotherapy of chronic lymphocytic leukemia. We have recently described a new metabolic path for the decomposition of 1 in human gastric juice based on its reactions with saliva-derived thiocyanate io...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx980122t

    authors: Hovinen J,Pettersson-Fernholm T,Lahti M,Vilpo J

    更新日期:1998-11-01 00:00:00

  • Activation of phospholipase A2 in 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine liposomes containing lipid ozonation products.

    abstract::The activation of phospholipase A2 (PLA2) by lipid ozonation products is reported. The principal products from the ozonation of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) are 1-palmitoyl-2-[8-[3(5-octyl-1,2,4-trioxolan-3-yl)octanoyl]--sn-gly cero-3- phosphocholine (PC-Criegee ozonide) and 1-palmitoyl-2-(9...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx00039a026

    authors: Salgo MG,Squadrito GL,Pryor WA

    更新日期:1994-05-01 00:00:00

  • Dityrosine cross-linked Abeta peptides: fibrillar beta-structure in Abeta(1-40) is conducive to formation of dityrosine cross-links but a dityrosine cross-link in Abeta(8-14) does not induce beta-structure.

    abstract::Recent reports by Galeazzi and co-workers demonstrated the susceptibility of Abeta(1-42) to undergo dityrosine formation via peroxidase-catalyzed tyrosine cross-linking. We have formed dityrosine cross-links in Abeta(1-40) using these enzymatic conditions as well as a copper-H(2)O(2) method. The efficiency of dityrosi...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx025666g

    authors: Yoburn JC,Tian W,Brower JO,Nowick JS,Glabe CG,Van Vranken DL

    更新日期:2003-04-01 00:00:00

  • Pharmacodynamics of cytochrome P450 2B induction by phenobarbital, 5-ethyl-5-phenylhydantoin, and 5-ethyl-5-phenyloxazolidinedione in the male rat liver or in cultured rat hepatocytes.

    abstract::The pharmacodynamics of rat hepatic cytochrome P450 2B (P450 2B) induction by phenobarbital (PB) and two structural congeners, dl-5-ethyl-5-phenylhydantoin (EPH) and dl-5-ethyl-5-phenyloxazolidinedione (EPO), were investigated. The in vivo induction of P450 2B was probed in F344/NCr rats by measuring immunoreactive he...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx00032a008

    authors: Nims RW,Sinclair PR,Sinclair JF,Thomas PE,Jones CR,Mellini DW,Syi JL,Lubet RA

    更新日期:1993-03-01 00:00:00

  • A Multiplatform Approach for the Discovery of Novel Drug-Induced Kidney Injury Biomarkers.

    abstract::Drug-induced kidney injury (DIKI) is a common toxicity observed in pharmaceutical development. We demonstrated the use of label-free liquid chromatography-mass spectrometry (LC-MS) and multiplex liquid chromatography-single reaction monitoring (LC-SRM) as practical extensions of standard immunoassay based safety bioma...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/acs.chemrestox.7b00159

    authors: Chen L,Smith J,Mikl J,Fryer R,Pack F,Williams BJ,Phillips JA,Papov VV Jr

    更新日期:2017-10-16 00:00:00

  • Oxidative DNA damage induced by activation of polychlorinated biphenyls (PCBs): implications for PCB-induced oxidative stress in breast cancer.

    abstract::We have previously reported that mono- and dichlorinated biphenyls (PCBs) can be metabolized to dihydroxy compounds and further oxidized to reactive metabolites which form adducts with nitrogen and sulfur nucleophiles including DNA [Amaro et al. (1966) Chem. Res. Toxicol. 9, 623-629; Oakley et al. (1996) Carcinogenesi...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx960103o

    authors: Oakley GG,Devanaboyina U,Robertson LW,Gupta RC

    更新日期:1996-12-01 00:00:00