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 animals exposed to EEA. Also, we found that EDE could modify hepatic protein by reaction with thiol groups and/or primary amines of protein. The present study was inclined to develop polyclonal antibodies to detect protein modified by EDE. An immunogen was prepared by reaction of EDE with keyhole limpet hemocyanin (KLH), and polyclonal antibodies were raised in rabbits immunized with the immunogen. Antisera collected from the immunized rabbits demonstrated high titers evaluated by enzyme-linked immunosorbent assays (ELISAs). Immunoblot analysis showed that the polyclonal antibodies recognized EDE-modified bovine serum albumin (BSA) in a hapten load-dependent manner but did not cross-react with native BSA. Competitive inhibition experiments elicited high selectivity of the antibodies toward EDE-modified BSA. The antibodies allowed us to detect and enrich EDE-modified protein in liver homogenates obtained from EEA-treated mice. The developed immunoprecipitation technique, along with mass spectrometry, enabled us to succeed in identifying multiple hepatic proteins of animals given EEA. We have successfully developed polyclonal antibodies with the ability to recognize EDE-derived protein adducts, which is a unique tool for us to define the mechanisms of toxic action of EEA.
journal_name
Chem Res Toxicoljournal_title
Chemical research in toxicologyauthors
Zhou S,Zhang N,Hu Z,Lin D,Li W,Peng Y,Zheng Jdoi
10.1021/acs.chemrestox.0c00016subject
Has Abstractpub_date
2020-07-20 00:00:00pages
1752-1760issue
7eissn
0893-228Xissn
1520-5010journal_volume
33pub_type
杂志文章abstract::Because of the association between inhalation of airborne particulate matter (PM) and human respiratory and cardiovascular disease, it is necessary to understand the tissue damage induced by these particles. One of the cell types principally involved in the body's reaction to PM are macrophages, which remove particles...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx034118f
更新日期:2004-01-01 00:00:00
abstract::The synthesis of a series of 1,2,4-triazole-containing oligopeptide lexitropsins related to the natural antitumor antibiotic distamycin is described. The binding properties of these new agents to both native DNAs and synthetic polydeoxyribonucleotides were determined by UV absorption and circular dichroism studies. Th...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00020a019
更新日期:1991-03-01 00:00:00
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
更新日期:2019-06-17 00:00:00
abstract::The location of carcinogen-modified nucleobases (DNA adducts) within DNA sequences is a critical factor affecting their promutagenic properties and persistence in DNA. We now report the use of controlled exonuclease digestion followed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MAL...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx010062i
更新日期:2001-08-01 00:00:00
abstract::Sudoxicam and meloxicam are nonsteroidal anti-inflammatory drugs (NSAIDs) from the enol-carboxamide class. While the only structural difference between the two NSAIDs is the presence of a methyl group on the C5-position of the 2-carboxamidothiazole motif in meloxicam, a marked difference in their toxicological profile...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx800185b
更新日期:2008-09-01 00:00:00
abstract::The use of powerful analytical technologies to detect endogenous carbonyls formed as byproducts of oxidative cell injury has revealed that these species contribute to many human diseases. As electrophiles, they are attacked by reactive centers in cell macromolecules to form adducts, the levels of which serve as useful...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx700399q
更新日期:2008-04-01 00:00:00
abstract::To prevent the accumulation of reactive oxygen species and limit associated damage to biological macromolecules, cells express a variety of oxidant-detoxifying enzymes, including peroxiredoxins. In Saccharomyces cerevisiae, the peroxiredoxin Tsa1 plays a key role in peroxide clearance and maintenance of genome stabili...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.8b00346
更新日期:2019-03-18 00:00:00
abstract::NADPH in microsomes reduces the hydroxocob(III)alamin form of vitamin B12 to cob(II)alamin and the supernucleophilic cob(I)alamin, which are both highly reactive toward xenobiotic epoxides formed by mammalian metabolism of dienes such as the industrially important chemicals chloroprene and 1,3-butadiene. With styrene,...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx0497898
更新日期:2004-12-01 00:00:00
abstract::Structure-function relationships for the inhibition of human cytochrome P450s (P450s) 1A1, 1A2, 1B1, 2C9, and 3A4 by 33 flavonoid derivatives were studied. Thirty-two of the 33 flavonoids tested produced reverse type I binding spectra with P450 1B1, and the potencies of binding were correlated with the abilities to in...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx100286d
更新日期:2010-12-20 00:00:00
abstract::Two novel pectenotoxins (PTXs) were detected by LC-MS in solid phase extracts of net hauls taken at Flødevigen, Norway, in June 2002 that were dominated by Dinophysis acuminata and Dinophysis norvegica. The new compounds were isolated as minor components from a large collection of a Dinophysis acuta-dominated bloom ob...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx049870a
更新日期:2004-11-01 00:00:00
abstract::The crystal structure of the food mutagen 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP) has been determined by single-crystal X-ray crystallography. Crystals grown by evaporation of an aqueous solution form in the monoclinic space group P2(1)/n with two molecules of PhIP per asymmetric unit, along with six w...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx950168b
更新日期:1996-04-01 00:00:00
abstract::Rutaevin is one of the major bioactive constituents isolated from Evodia rutaecarpa, a well-known herbal medicine that has been widely prescribed for the treatment of gastrointestinal disorders in China. However, oral administration of rutaevin has been shown to cause hepatotoxicity in mice. Bioactivation was suggeste...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.0c00475
更新日期:2020-12-21 00:00:00
abstract::Because the manganese-based contrast agents used in magnetic, resonance imaging are unstable in vivo, some concern exists about the potential toxicity coming from the Mn2+ released by the complexes. This potential problem arises because the manganese is known to accumulate in the brain of people intoxicated by this me...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx960194p
更新日期:1997-04-01 00:00:00
abstract::In vitro techniques have been utilized to investigate the microsomal enzymes involved in the metabolism of lauric acid and to establish conditions in which it can be used as a model substrate for both cytochrome P450 4A and cytochrome P450 2E1 in human liver microsomes. Studies of enzyme kinetics of lauric acid omega-...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00042a018
更新日期:1994-11-01 00:00:00
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
更新日期:2013-01-18 00:00:00
abstract::Exposure to aristolochic acid I (AAI) is associated with aristolochic acid nephropathy, Balkan endemic nephropathy, and urothelial cancer. Individual differences in xenobiotic-metabolizing enzyme activities are likely to be a reason for interindividual susceptibility to AA-induced disease. We evaluated the reductive a...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx200259y
更新日期:2011-10-17 00:00:00
abstract::Marine toxins such as brevetoxins and ciguatoxins are produced by dinoflagellates and can accumulate in seafood. These toxins affect humans through seafood consumption. Intoxication is mainly characterized by gastrointestinal and neurological disorders and, in most severe cases, by cardiovascular problems. To prevent ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx0342262
更新日期:2004-04-01 00:00:00
abstract::A new procedure has been developed for the extraction of 2-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine (PhIP) and other heterocyclic aromatic amines from human breast milk samples. Extracts were analyzed by high-performance liquid chromatography/electrospray ionization/tandem mass spectrometry (HPLC/ESI-MS/MS) with...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx0601861
更新日期:2007-01-01 00:00:00
abstract::Reactive oxygen species can induce the formation of tandem DNA lesions. We recently showed that the treatment of calf thymus DNA with Cu2+/H2O2/ascorbate could result in the efficient formation of a tandem lesion where a 5,6-dihydroxy-5,6-dihydrothymidine (or thymidine glycol) is situated on the 5' side of an 8-oxo-7,...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx8003449
更新日期:2009-03-16 00:00:00
abstract::Prolonged ingestion of Yellow Starthistle (Centaurea solstitialis) and Russian Knapweed (Centaurea repens) by horses has been shown to result in a fatal neurodegenerative disorder called equine nigropallidal encephalomalacia (ENE). Bioassay-guided fractionation of extracts from Centaurea species using the PC12 cell li...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx049864e
更新日期:2004-09-01 00:00:00
abstract::Contact allergy is caused by a wide range of chemicals after skin contact. Its clinical manifestation, allergic contact dermatitis (ACD), is developed upon repeated contact with the allergen. This perspective focuses on two areas that have yielded new useful information during the last 20 years: (i) structure-activity...
journal_title:Chemical research in toxicology
pub_type: 杂志文章,评审
doi:10.1021/tx7002239
更新日期:2008-01-01 00:00:00
abstract::The .CCl3 radical generated during the metabolism of CCl4 is readily spin trapped in vivo and in vitro by phenyl N-tert-butylnitrone (PBN) to form the stable PBN/.CCl3 radical adduct, which can then be extracted into organic solvents and detected by ESR spectroscopy. We have used this technique to examine the proposed...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00035a017
更新日期:1993-09-01 00:00:00
abstract::This study was designed to distinguish and evaluate the contribution of reactive metabolite and reactive oxygen species as the mechanism of metabolism-dependent valproic acid-induced in vitro cytotoxicity. The involvement of reactive oxygen species in the mechanism of in vitro cytotoxicity was examined by the addition...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx9801864
更新日期:1999-04-01 00:00:00
abstract::We have reassigned relative and absolute configurations by unambiguous stereoselective syntheses of the cis- (13s and 13R) and trans-N6-deoxyadenosine (dAdo) adduct diastereomers (14S and 14R) derived from (+/-)-11beta,12alpha-dihydroxy-13alpha,14alpha-epoxy-11,12,13,14-tetrahydrodibenzo[a,l]pyrene (DB[a,l]P DE-2), pr...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx800268f
更新日期:2008-12-01 00:00:00
abstract::Arylamines (AAs) and heterocyclic aromatic amines (HAAs) are structurally related carcinogens formed during the combustion of tobacco or cooking of meat. They undergo cytochrome P450 mediated N-hydroxylation to form metabolites which bind to DNA and lead to mutations. The N-hydroxylated metabolites of many AAs also ca...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.5b00418
更新日期:2016-03-21 00:00:00
abstract::Faithful replication of DNA is a critical aspect in maintaining genome integrity. DNA polymerases are responsible for replicating DNA, and high-fidelity polymerases do this rapidly and at low error rates. Upon exposure to exogenous or endogenous substances, DNA can become damaged and this can alter the speed and fidel...
journal_title:Chemical research in toxicology
pub_type: 杂志文章,评审
doi:10.1021/acs.chemrestox.7b00224
更新日期:2017-11-20 00:00:00
abstract::The environmental contaminant benzo[c]phenanthrene (B[c]Ph) has weak carcinogenic activity in rodent bioassays; however, the fjord region diol epoxides of B[c]Ph, B[c]Ph-3,4-diol 1,2-epoxides (B[c]PhDE), are potent carcinogens. To determine the role of cytochrome P450 isozymes in the activation of B[c]Ph in MCF-7 cell...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx960174n
更新日期:1997-05-01 00:00:00
abstract::Reaction of lysine with estrone 3,4-o-quinone gave a complex mixture of products. Six compounds were isolated and identified using spectroscopic techniques. Among the reaction products isolated were 4-hydroxyestrone (2), 3-aminoisoestrone (3), 3-(N-pentyl-5-amino)-isoestrone (4), 1-lysylestrone 3,4-o-iminoquinone (5),...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00041a016
更新日期:1994-09-01 00:00:00
abstract::The hydroperoxide of linoleic acid (13-HPODE) degrades to 9,12-dioxo-10(E)-dodecenoic acid (DODE), which readily modifies proteins. This study identified the major proteins in MCF7 cells modified by DODE. To reduce false positives, three methods were used to identify DODE-modified proteins. First, cells were treated w...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx9002808
更新日期:2010-03-15 00:00:00
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 B...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.0c00118
更新日期:2020-09-21 00:00:00