Abstract:
:Four novel cadmium-chelating agents N,N'di(D-glucosyl)alkanediamine-N,N'-bis(carbodithioates) 4a-e were prepared as disodium salts of the general formula (CH2)n[N(CS2Na)CH2(CHOH)4CH2OH]2, where n = 7, 8, 10, and 12. They were synthesized by the reductive coupling of 2 mol of alpha-D-(+)-glucose (1) with 1 mol of the corresponding alkanediamines 2a-e followed by reaction with CS2 in a basic medium. The elemental analyses of the Cd complexes 5a, b, d, and e prepared revealed that these bis(carbodithioates) form 1:1 complexes with Cd2+. The in vivo cadmium-mobilizing efficacy of three of the new chelators (4a, b, and d) was determined in rats pretreated ip with CdCl2.H2O containing 2 microCi of 109Cd (74 kBq), and comparable data were obtained on a previously reported member of this series (4c, n = 9), and with BGDTC (sodium N-benzyl-D-glucamine-N-carbodithioate, 6), all given once at 1.0 mmol/kg ip. The compound with n = 12 (4e, C12G2DTC) proved to be too toxic in the preliminary study and was not evaluated further. A single injection of the 4a, b, and d caused a reduction in Cd levels of the whole body to ca. 50% and liver to ca. 12% of control levels. Comparable experimental data on BGDTC resulted in a reduction of whole-body cadmium to only 78% of the control levels and a reduction in liver cadmium to only 56% of control. After one and six injections at the same dosage, the new chelators (4a, b, and d) and C9G2DTC (4c, n = 9) significantly surpassed BGDTC for whole-body and liver Cd depletion but caused only a very modest depletion of renal Cd. While these compounds were designed to allow the two dithiocarbamate groups to coordinate to the same Cd2+ in vivo, the data do not prove that the two > NCS2Na groups bind to the same cadmium ion in vivo. The very rapid reduction in liver cadmium levels following only a single injection indicates that these -2 anions rapidly gain access to intracellular hepatic sites by some transport system.
journal_name
Chem Res Toxicoljournal_title
Chemical research in toxicologyauthors
Singh PK,Jones MM,Kostial K,Blanusa M,Piasek Mdoi
10.1021/tx950123asubject
Has Abstractpub_date
1996-01-01 00:00:00pages
313-7issue
1eissn
0893-228Xissn
1520-5010pii
tx950123ajournal_volume
9pub_type
杂志文章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::A series of 13 cyclopenta polycyclic aromatic hydrocarbons have been studied using quantum mechanical methods. The three-dimensional molecular structure of each carbocation that might result from the opening of a protonated epoxide ring formed between the carbon atoms completing the cyclopenta ring was computed with A...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00026a022
更新日期:1992-03-01 00:00:00
abstract::By the action of UVA light, fluphenazine reacted with nucleophiles through a mechanism involving defluorination of its trifluoromethyl group, giving rise to carboxylic acid derivatives that were easily detected by electrospray mass spectrometry. This photoreaction took place with alcohols, sulphydryls, and amines. Whe...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx700123u
更新日期:2007-10-01 00:00:00
abstract::Diastereomeric 8,5'-cyclopurine 2'-deoxynucleosides, containing a covalent bond between the deoxyribose and the purine base, are induced in DNA by ionizing radiation. They are suspected to play a role in the etiology of neurodegeneration in xeroderma pigmentosum patients. If not repaired, the S-8,5'-cyclo-2'-deoxyguan...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx2005053
更新日期:2012-02-20 00:00:00
abstract::Green tea catechins and hydrolyzable tannins are gaining increasing attention as chemopreventive agents. However, their mechanism of action is poorly understood. We investigated the effects of four green tea catechins and two hydrolyzable tannins on microsome-induced benzo[a]pyrene (BP)-DNA adducts and the possible st...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx900412a
更新日期:2010-04-19 00:00:00
abstract::Spin-trapping with 5,5-dimethyl-1-pyrroline 1-oxide (DMPO) was used to demonstrate that 3-nitrotyrosine (nitrotyrosine) promotes the formation of substantial amounts of reactive oxygen species (O2.- and *OH), when incubated with NAD(H)-cytochrome c reductase and a corresponding electron donor. Spin adduct formation is...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx970201p
更新日期:1998-05-01 00:00:00
abstract::Exposure to arsenic affects large human populations worldwide and has been associated with a long list of human diseases, including skin, bladder, lung, and liver cancers, diabetes, and cardiovascular disorders. In addition, there are large individual differences in susceptibility to arsenic-induced diseases, which ar...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx4002868
更新日期:2013-12-16 00:00:00
abstract::Sex-, species-, and chain length-dependent renal elimination is the hallmark of mammalian elimination of perfluorocarboxylates (PFCAs) and has been extensively studied for almost 30 years. In this review, toxicokinetic data of PFCAs (chain lengths ranging from 4 to 10) in different species are compared with an emphasi...
journal_title:Chemical research in toxicology
pub_type: 杂志文章,评审
doi:10.1021/tx200363w
更新日期:2012-01-13 00:00:00
abstract::The role of prostaglandin H synthase-1 (PHS-1) and a related model enzyme, horseradish peroxidase (HRP), in catalyzing the bioactivation of dopamine (DA) and epinephrine and their precursors and metabolites to potential neurodegenerative free radical intermediates was examined. To determine the potential contribution ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx800423s
更新日期:2009-05-01 00:00:00
abstract::MXenes have attracted extensive attention due to their unique physicochemical properties. Especially, the flexibility and good conductivity endow MXenes with a great application prospect in the neural interfaces. However, the cytotoxicity of MXenes to nervous system remains unclear. In this study, we evaluated the cyt...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.0c00232
更新日期:2020-12-21 00:00:00
abstract::Tocopherols (alpha-, beta-, gamma-, and delta-Toc) and tocopheryl quinones (alpha-, beta-, gamma-, and delta-TQ) were recently suggested to modulate mitochondrial electron transfer in mammals. Intriguingly, Tocs and stigmatellin, a potent inhibitor of the mitochondrial cytochrome (cyt) bc(1) complex, possess a common ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx900333f
更新日期:2010-01-01 00:00:00
abstract::Chromium(III) tris(picolinate) [Cr(pic)3] is currently a very popular nutritional supplement; however, its safety has recently been questioned, especially with regard to its ability to act as a clastogen. At physiologically relevant concentrations, Cr(pic)3 is reduced by biological reductants, including ascorbate and ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx9900167
更新日期:1999-06-01 00:00:00
abstract::Ochratoxin A (OTA) is a mycotoxin that shows potent nephrotoxicity and renal carcinogenicity in rodents. One hypothesis for OTA-induced tumor formation is based on its genotoxic properties that are promoted by oxidative metabolism. Like other chlorinated phenols, OTA undergoes an oxidative dechlorination process to ge...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx060138g
更新日期:2006-09-01 00:00:00
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
更新日期:2017-10-16 00:00:00
abstract::An increased risk of breast cancer has been observed in women who consume "very well-done" meats. Heterocyclic amines are mutagenic and carcinogenic pyrolysis products formed during high temperature cooking of meats. In the present study, human milk samples were analyzed for PhIP, one of the most abundant dietary hete...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx015556u
更新日期:2001-11-01 00:00:00
abstract::Cytochrome P-450 enzymes have been postulated to oxidize amines through a variety of mechanisms. One of the means of distinguishing among potential pathways involves the use of kinetic hydrogen isotope effects: low isotope effects are characteristic of aminium radical mechanisms while high values are consistent with h...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00013a004
更新日期:1990-01-01 00:00:00
abstract::Two 2-aminofluorene-derived hydroxamic acids that differ only in the nature of the N-acyl group were examined for their relative abilities to undergo covalent binding to nucleic acids. Studies of the bioactivation of N-hydroxy-N-acetyl-2-aminofluorene (N-OH-AAF) and N-hydroxy-N-glycolyl-2-aminofluorene (N-OH-GAF) were...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00001a008
更新日期:1988-01-01 00:00:00
abstract::The oral dipeptidyl peptidase 1 (DPP1) inhibitor AZD5248 showed aortic binding in a rat quantitative whole-body autoradiography (QWBA) study, and its development was terminated prior to human dosing. A mechanistic hypothesis for this finding was established invoking reactivity with aldehydes involved in the cross-link...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.5b00236
更新日期:2015-10-19 00:00:00
abstract::Raloxifene (Evista) is a second generation selective estrogen receptor modulator used in the treatment of osteoporosis and for chemoprevention of breast cancer. It is bioactivated to reactive intermediates, which covalently bind to proteins and form GSH conjugates upon incubation with NADPH and GSH-supplemented human ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx800323w
更新日期:2008-12-01 00:00:00
abstract::Hemoglobin adducts have been used to assess exposure to carcinogenic compounds in tobacco smoke. However, because of background levels in nonsmokers, most adducts that have been studied are not useful for monitoring low-level exposure. Bergmark [(1997) Chem. Res. Toxicol. 10, 78-84] showed that the level of adducts of...
journal_title:Chemical research in toxicology
pub_type: 临床试验,杂志文章
doi:10.1021/tx9900728
更新日期:1999-10-01 00:00:00
abstract::Exposure to inorganic arsenic (iAs) induces cancer in human lungs, urinary bladder, skin, kidney, and liver, with the majority of deaths from lung and bladder cancer. To date, cancer risk assessments for iAs have not relied on mechanistic data, as we have lacked sufficient understanding of arsenic's pharmacokinetics a...
journal_title:Chemical research in toxicology
pub_type: 杂志文章,评审
doi:10.1021/tx900343d
更新日期:2010-02-15 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::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::Liver microsomes from uninduced hogs catalyzed the NADPH-dependent N-oxidation of the hydroxylamine (Z)-3-(4-bromophenyl)-N-hydroxy-N-methyl-3-(3-pyridyl)allylamine. The conjugated nitrone N-[(2Z)-3-(4-bromophenyl)-3-(3-pyridyl)-2-propenylidene]methylamin e N-oxide was the principal product and accounted for 90-95% of...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00017a007
更新日期:1990-09-01 00:00:00
abstract::Carbon disulfide (CS2) induces embryo implantation disorders. Macrophages participate in the process of pregnancy. Therefore, we want to explore the effects of CS2 exposure on polarization and immune function of macrophages in pregnant mice uteri. The exposure times were gestation days 3 (GD3), 4 (GD4), and 5 (GD5), a...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.9b00119
更新日期:2019-10-21 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::S-(1,2-Dichlorovinyl)-L-cysteine (DCVC), a mutagenic and nephrotoxic metabolite of trichloroethylene, is bioactivated to S-(1,2-dichlorovinyl)-L-cysteine sulfoxide (DCVCS) and chlorothioketene and/or 2-chlorothionoacetyl chloride by cysteine conjugate S-oxidase (S-oxidase) and cysteine conjugate beta-lyase (beta-lyase...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx900219x
更新日期:2009-09-01 00:00:00
abstract::8-Aminoguanine had previously been identified as one of the nucleic acid base modifications produced in livers of rats by treatment with the hepatocarcinogen 2-nitropropane (2-NP), and a hypothetical mechanism of activation of 2-NP to hydroxylamine-O-sulfonate or acetate that would lead to NH2+, an aminating species, ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00039a011
更新日期:1994-05-01 00:00:00
abstract::Pyrrolizidine alkaloids (PAs) are known hepatotoxins. The execution of the toxicities of the alkaloids requires metabolic activation. Protein modification by reactive metabolites of PAs has been suggested to be an important mechanism of the toxic actions of PAs. The objectives of the present study were to define the i...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.5b00488
更新日期:2016-03-21 00:00:00
abstract::Ferroptosis is a form of cell death that requires phospholipid peroxidation and has attracted increased attention, both as a means to eradicate tumors resistant to standard chemotherapy and for its potential contribution to tissue damage such as in ischemia/reperfusion. The center stage taken by phospholipid peroxidat...
journal_title:Chemical research in toxicology
pub_type: 杂志文章,评审
doi:10.1021/acs.chemrestox.8b00349
更新日期:2019-03-18 00:00:00