Abstract：
:Divicine is an unstable aglycon metabolite of the fava bean pyrimidine beta-glucoside vicine. Divicine has long been thought to be a mediator of an acute hemolytic crisis, known as favism, in susceptible individuals who ingest fava beans (Vicia faba). However, a recent report has questioned the chemical identity of the divicine that was used in most of the studies on divicine hemotoxicity. The present study was undertaken to examine the hemolytic potential of synthetic divicine. Divicine was synthesized and its identity and purity were confirmed by HPLC, mass spectrometry, and NMR spectroscopy. The stability and redox behavior of divicine, under physiological conditions, were examined by HPLC and cyclic voltammetry. The data indicate that divicine is readily oxidized under aerobic conditions; however, it was sufficiently stable at pH 7.4 to permit its experimental manipulation. When 51Cr-labeled rat erythrocytes were exposed in vitro to the parent glucoside, vicine (5 mM), and then readministered to rats, no decrease in erythrocyte survival was observed. In contrast, erythrocyte survival was dramatically reduced by in vitro exposure to divicine (1.5 mM). These data demonstrate that divicine is a direct-acting hemolytic agent and thus may be a mediator of the hemolytic crisis induced by fava bean ingestion.
journal_name
Chem Res Toxicoljournal_title
Chemical research in toxicologyauthors
McMillan DC,Schey KL,Meier GP,Jollow DJdoi
10.1021/tx00034a009subject
Has Abstractpub_date
1993-07-01 00:00:00pages
439-44issue
4eissn
0893-228Xissn
1520-5010journal_volume
6pub_type
杂志文章abstract：:Previous studies suggested that lamotrigene (LTG) underwent bioactivation to a reactive aryl epoxide intermediate in rats. Nevertheless, definitive structures of these thioether conjugates, which are often needed to substantiate the mechanism of bioactivation and identity of reactive intermediate(s), were not fully es...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx9003243
更新日期：2010-01-01 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：:The reaction of the antitumor agent leinamycin with thiols converts this natural product into an episulfonium ion that alkylates the N7-position of guanine residues in double-stranded DNA. It is reported here that depurination of this adduct is unusually facile, occurring with a half-life of about 3.5 h at pH 7 and 37...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx049964k
更新日期：2004-07-01 00:00:00
abstract：:The procarcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is the most abundant heterocyclic amine formed during the cooking of foods. Metabolism of PhIP by CYP1A2 differs substantially between humans and rodents, with more N2-hydroxylation (activation) and less 4'-hydroxylation (detoxication) in humans....
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx050136g
更新日期：2005-09-01 00:00:00
abstract：:Dibenzo[a,l]pyrene (DB[a,l]P) is one of the most potent carcinogens ever tested in mouse skin and rat mammary gland. DB[a,l]P is present in cigarette smoke and, presumably, in other environmental pollutants. Metabolism and mutagenicity studies of this compound compared to the weak carcinogen dibenzo[a,e]pyrene (DB[a,e...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx00018a014
更新日期：1990-11-01 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：:DNA nucleobases are the prime targets for chemical modifications by endogenous and exogenous electrophiles. Alkylation of the N7 position of guanine and adenine in DNA triggers base-catalyzed imidazole ring opening and the formation of N5-substituted formamidopyrimidine (N5-R-FAPy) lesions. Me-FAPy-dG adducts induced ...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.6b00392
更新日期：2017-01-17 00:00:00
abstract：:Hypoxia-inducible factor-1 alpha (HIF-1 alpha) and the aryl hydrocarbon receptor (AhR) work as environmental sensors in human tissues. These proteins are members of the helix-loop-helix/Per-ARNT-SIM transcription factor family and form heterodimers with the aryl hydrocarbon receptor nuclear translocator. HIF-1 alpha c...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx7001838
更新日期：2008-02-01 00:00:00
abstract：:Acrolein is a bifunctional electrophile, present as an ubiquitous environmental pollutant and an endogenous cellular product of lipid peroxidation. Reaction of acrolein with deoxyguanosine produces two regioisomeric DNA adducts, specifically gamma-hydroxypropanodeoxyguanosine (gamma-HOPdG) and alpha-hydroxypropanodeox...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx034066u
更新日期：2003-08-01 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：:The conformation of the crotonaldehyde-derived N(2)-[3-oxo-1(S)-methyl-propyl]-dG adduct in the oligodeoxynucleotide 5'-d(G(1)C(2)T(3)A(4)G(5)C(6)X(7)A(8)G(9)T(10)C(11)C(12))-3'.5'-d(G(13)G(14)A(15)C(16)T(17)C(18)G(19)C(20)T(21)A(22)G(23)C(2)(4))-3', where X = N(2)-[3-oxo-1(S)-methyl-propyl]-dG, is reported. This addu...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx0600604
更新日期：2006-08-01 00:00:00
abstract：:The issue of the safety of drug metabolites in humans is a complex one. In this commentary, a proposal is made regarding how to deal with drug metabolites observed in humans such that the safety of these molecules can be assured. The human radiolabeled ADME study, in which metabolites are identified and quantified in ...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx0602012
更新日期：2006-12-01 00:00:00
abstract：:Drug hypersensitivity reactions adversely affect treatment outcome, increase the length of patients' hospitalization, and limit the prescription options available to physicians. In addition, late stage drug attrition and the withdrawal of licensed drugs cost the pharmaceutical industry billions of dollars. This signif...
journal_title：Chemical research in toxicology
pub_type： 杂志文章,评审
doi：10.1021/acs.chemrestox.9b00327
更新日期：2020-01-21 00:00:00
abstract：:The toxicity of paraquat (PQ2+) is attributed to intracellularly formed PQ*+, O(2)*-, H(2)O(2), and secondary.OH radicals generated through Fenton-like reactions. Yet, no antidote for PQ2+ toxicity in human has been found also due to poor cell permeability of many common antioxidants that remove toxic species predomin...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx0155956
更新日期：2002-05-01 00:00:00
abstract：:Finger 3 of transcription factor IIIA of Xenopus laevis was synthesized and constituted with Zn(2+) or Cd(2+). The C-block element of the internal control region of the promoter of the 5S rRNA gene binds to the Zn-F3 and Cd-F3 with dissociation constants of 2.6 x 10(-5) and 1.5 x 10(-4) M, respectively. According to N...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx030057+
更新日期：2004-07-01 00:00:00
abstract：:Two hemorrhagic proteases, Lachesis hemorrhagic toxins a and b (LHTa and LHTb), were isolated from the venom of Lachesis muta, which is distributed in Central and South America. One protease showed strong hemorrhagic action, while the other showed weak hemorrhagic activity even though the two enzymes are very similar ...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx00006a003
更新日期：1988-11-01 00:00:00
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
更新日期：2007-10-01 00:00:00
abstract：:The diarrhetic shellfish toxin composition in the digestive glands of mussels collected in June 2001 from the Northern Adriatic sea was investigated by high-performance liquid chromatography coupled with electrospray ion trap mass spectrometry. Along with known yessotoxins (1, 3-6), identified by comparison of their r...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx025527z
更新日期：2002-07-01 00:00:00
abstract：:Elevated levels of the estrone metabolite, 16α-hydroxyestrone (16αOHE1), have been linked with multiple diseases. As an electrophilic reactive metabolite, covalent binding to proteins is thought to constitute one of the possible mechanisms in the onset of deleterious health outcomes associated with 16αOHE1. Whereas ma...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.0c00171
更新日期：2020-08-17 00:00:00
abstract：:Cryogenic (4-10 K) laser-induced vibrationless ground state and vibronic excited state fluorescence emission spectra of the adducts resulting from reaction in vitro of human serum albumin and the carcinogen (+-)-r-7,t-8-dihydroxy-c-9,c-10-epoxy-7,8,9,10- tetrahydrobenzo[a]-pyrene were recorded in order to determine th...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx00025a012
更新日期：1992-01-01 00:00:00
abstract：:The preparation and DNA binding characteristics of a structural analog of Hoechst 33258 bearing two pyridinic nitrogen atoms are described. The 1H NMR signals of the complex formed between the new ligand 1 and decadeoxyribonucleotide d(CATGGCCATG)2 were assigned by employing one- and two-dimensional NMR techniques. In...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx00029a003
更新日期：1992-09-01 00:00:00
abstract：:A series of (alkylthio)trifluoropropanones containing a heterocyclic moiety was synthesized. The compounds were tested for in vitro inhibition of four hydrolytic enzymes including insect juvenile hormone esterase (JHE), eel acetylcholinesterase (AChE), yeast lipase (LP), and bovine alpha-chymotrypsin. The I50 values r...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx00016a009
更新日期：1990-07-01 00:00:00
abstract：:Evidence from laboratory studies and clinical trials suggests that plant-derived polyphenolic compounds such as curcumin, resveratrol, or phloretin might be useful in the treatment of certain diseases (e.g., Alzheimer's disease) and acute tissue injury states (e.g., spinal cord trauma). However, despite this potential...
journal_title：Chemical research in toxicology
pub_type： 杂志文章,评审
doi：10.1021/acs.chemrestox.6b00300
更新日期：2016-12-19 00:00:00
abstract：:The major plant growth regulator ethephon degrades to ethylene and phosphate in aqueous solutions and plants and is spontaneously activated to a butyrylcholinesterase (BChE) inhibitor in alkaline solutions and animal tissues. In the present (31)P NMR kinetic study of the reactions of ethephon in pH 7.4 carbonate buffe...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx4002429
更新日期：2013-09-16 00:00:00
abstract：:Antineoplastic therapy with anthracyclines like doxorubicin (DOX) and daunorubicin (DNR) is limited by the possible development of a dose-related cardiomyopathy. Secondary alcohol metabolites like doxorubicinol (DOXol) and daunorubicinol (DNRol), formed by cytoplasmic two-electron reductases, have been implicated as p...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx060159a
更新日期：2006-11-01 00:00:00
abstract：:Carcinogens induce complex transcriptional responses in cells that may hold key mechanistic information. Benzo(a)pyrene (BaP) modulation of transcription may occur through the activation of the aryl hydrocarbon receptor (AHR) or through responses to DNA damage. To characterize further the expression profiles induced b...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx700252n
更新日期：2007-12-01 00:00:00
abstract：:Electrochemical oxidation of drug molecules is a useful tool to generate several different types of metabolites. In the present study we developed a model system involving electrochemical oxidation followed by characterization of the oxidation products and their propensity to modify peptides. The CB1 antagonist rimona...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx500255r
更新日期：2014-10-20 00:00:00
abstract：:Formyl chloride has been indirectly implicated as an intermediate in the oxidation of CH(2)Cl(2) and proposed to be a product of the oxidation of some other compounds. Formyl chloride was synthesized and added to aqueous solutions, with CO formed as a product. The presence of glutathione (GSH) did not reduce the yield...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx060087n
更新日期：2006-08-01 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：:4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N'-nitrosonornicotine (NNN) are important human carcinogens in tobacco products. They are metabolized to produce a variety 4-(3-pyridyl)-4-oxobutyl (POB) DNA adducts including O(2)-[4-(3-pyridyl)-4-oxobut-1-yl]thymidine (O(2)-POB-dT), the most abundant POB adduc...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.5b00468
更新日期：2016-03-21 00:00:00
