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

authors： Shimada T,Tanaka K,Takenaka S,Murayama N,Martin MV,Foroozesh MK,Yamazaki H,Guengerich FP,Komori M

更新日期：2010-12-20 00:00:00

abstract：:Hydrophobic and volatile chemicals have proven to be difficult to dose in cell assays. Cosolvents are often needed to dissolve these chemicals in cell culture medium. Moreover, the free concentration of these chemicals in culture medium may diminish over time due to metabolism, evaporation, and nonspecific binding to ...

journal_title：Chemical research in toxicology

authors： Kramer NI,Busser FJ,Oosterwijk MT,Schirmer K,Escher BI,Hermens JL

更新日期：2010-11-15 00:00:00

abstract：:Acrolein (AC) and 4-hydroxy-2-nonenal (HNE) are endogenous bis-electrophiles that arise from the oxidation of polyunsaturated fatty acids. AC is also found in high concentrations in cigarette smoke and automobile exhaust. These reactive α,β-unsaturated aldehyde (enal) covalently modify nucleic acids, to form exocyclic...

journal_title：Chemical research in toxicology

authors： Kozekov ID,Turesky RJ,Alas GR,Harris CM,Harris TM,Rizzo CJ

更新日期：2010-11-15 00:00:00

abstract：:3-Methylindole (3MI) is a preferential pneumotoxicant found in cigarette smoke. A number of lung-expressed human cytochrome P450 enzymes, including 1A1, 2F1, and 2A13, catalyze the metabolism of 3MI to reactive intermediates that fragment DNA, measured with the Comet assay to assess DNA damage, in a cytochrome P450-de...

journal_title：Chemical research in toxicology

authors： Weems JM,Lamb JG,D'Agostino J,Ding X,Yost GS

更新日期：2010-11-15 00:00:00

abstract：:Protein-xenobiotic adducts are byproducts of xenobiotic metabolism. While there is a correlation between protein adduction and target organ toxicity, a cause and effect relationship is not often clear. Naphthoquinone (NQ) and monocrotaline pyrrole (MCTP) are two pneumotoxic electrophiles that form covalent adducts wit...

journal_title：Chemical research in toxicology

authors： Nakayama Wong LS,Lamé MW,Jones AD,Wilson DW

更新日期：2010-09-20 00:00:00

abstract：:The conjugation of reactive drug metabolites to GSH is considered an important detoxification mechanism that can be spontaneous and/or mediated by glutathione S-transferases (GSTs). In case GSTs play an important role in GSH conjugation, genetically determined deficiencies in GSTs may be a risk factor for adverse drug...

journal_title：Chemical research in toxicology

authors： Dragovic S,Boerma JS,van Bergen L,Vermeulen NP,Commandeur JN

更新日期：2010-09-20 00:00:00

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

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

更新日期：2010-08-16 00:00:00

abstract：:(R)-Thalidomide was oxidized to 5-hydroxythalidomide and 5'-hydroxythalidomide by NADPH-fortified liver microsomes from humans and monkeys. (R)-Thalidomide was hydroxylated more efficiently than (S)-thalidomide. Recombinant human P450s 3A4, 3A5, and 3A7 and monkey P450s 3A8 and 3A5 (coexpressed with NADPH-P450 reducta...

journal_title：Chemical research in toxicology

authors： Chowdhury G,Murayama N,Okada Y,Uno Y,Shimizu M,Shibata N,Guengerich FP,Yamazaki H

更新日期：2010-06-21 00:00:00

abstract：:Sulfamethoxazole (SMX) is an important antibiotic in the management of patients with cystic fibrosis, but allergic reactions may develop thus restricting therapy. The aim of this study was to utilize drug (metabolite) antigens to diagnose SMX-mediated allergic reactions in patients with cystic fibrosis. Lymphocytes fr...

journal_title：Chemical research in toxicology

authors： Lavergne SN,Whitaker P,Peckham D,Conway S,Park BK,Naisbitt DJ

更新日期：2010-06-21 00:00:00

abstract：:Mouse cytochrome P450 2A5 (CYP2A5) is upregulated in various pathophysiological liver diseases and induced by structurally variable hepatotoxic chemicals. A putative common feature for all of these conditions is altered cellular redox status. Nuclear factor erythroid 2-like 2 (Nrf2) is a transcription factor that is p...

journal_title：Chemical research in toxicology

authors： Lämsä V,Levonen AL,Leinonen H,Ylä-Herttuala S,Yamamoto M,Hakkola J

更新日期：2010-05-17 00:00:00

abstract：:Coumadin (R/S-warfarin) anticoagulant therapy poses a risk to over 50 million Americans, in part due to interpersonal variation in drug metabolism. Consequently, it is important to understand how metabolic capacity is influenced among patients. Cytochrome P450s (P450 or CYP for a specific isoform) catalyze the first m...

journal_title：Chemical research in toxicology

authors： Jones DR,Kim SY,Guderyon M,Yun CH,Moran JH,Miller GP

更新日期：2010-05-17 00:00:00

abstract：:Adverse effects of drugs (AEDs) continue to be a major cause of drug withdrawals in both development and postmarketing. While liver-related AEDs are a major concern for drug safety, there are few in silico models for predicting human liver toxicity for drug candidates. We have applied the quantitative structure-activi...

journal_title：Chemical research in toxicology

authors： Rodgers AD,Zhu H,Fourches D,Rusyn I,Tropsha A

更新日期：2010-04-19 00:00:00

abstract：:The C2'-oxidized abasic lesion (C2-AP) is produced in DNA that is subjected to oxidative stress. The lesion disrupts replication and gives rise to mutations that are dependent upon the identity of the upstream nucleotide. Ape1 incises C2-AP, but the 5'-phosphorylated fragment is not a substrate for the lyase activity ...

journal_title：Chemical research in toxicology

authors： Wong RS,Sczepanski JT,Greenberg MM

更新日期：2010-04-19 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

authors： Cao P,Cai J,Gupta RC

更新日期：2010-04-19 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

authors： Slade PG,Williams MV,Brahmbhatt V,Dash A,Wishnok JS,Tannenbaum SR

更新日期：2010-03-15 00:00:00

abstract：:Alzheimer's disease (AD) is the most common neurodegenerative disorder in the elderly population, above 65 years of age. Multiple lines of evidence confirm the central role of 40-42 residue Abeta peptides in the pathogenesis of AD, but exact mechanisms of Abeta toxicity remain unclear. Recently, evidence has accumulat...

journal_title：Chemical research in toxicology

authors： Rózga M,Bal W

更新日期：2010-02-15 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

authors： Kitchin KT,Conolly R

更新日期：2010-02-15 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

authors： Müllebner A,Patel A,Stamberg W,Staniek K,Rosenau T,Netscher T,Gille L

更新日期：2010-01-01 00:00:00

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

authors： Chen H,Grover S,Yu L,Walker G,Mutlib A

更新日期：2010-01-01 00:00:00

abstract：:The urine from mice exposed to styrene vapors (600 and 1200 mg/m(3), 6 h) was analyzed for ring-oxidized metabolites of styrene. To facilitate the identification of metabolites in urine, the following potential metabolites were prepared: 2-, 3-, and 4-vinylphenol (2-, 3-, and 4-VP), 4-vinylpyrocatechol, and 2-, 3-, an...

journal_title：Chemical research in toxicology

authors： Linhart I,Mráz J,Scharff J,Krouzelka J,Dusková S,Nohová H,Vodicková L

更新日期：2010-01-01 00:00:00

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

authors： Wang H,Cao H,Wang Y

更新日期：2010-01-01 00:00:00

abstract：:This paper reports on the analysis of the toxin content from Palythoa tuberculosa and Palythoa toxica samples collected off of the Hawaiian coast. Our work, based on in-depth high-resolution liquid chromatography-mass spectrometry analysis along with extensive NMR study, led us to structurally characterize 42-hydroxy-...

journal_title：Chemical research in toxicology

authors： Ciminiello P,Dell'aversano C,Dello Iacovo E,Fattorusso E,Forino M,Grauso L,Tartaglione L,Florio C,Lorenzon P,De Bortoli M,Tubaro A,Poli M,Bignami G

更新日期：2009-11-01 00:00:00

abstract：:The clinically used antitumor antibiotic mitomycin C requires a reductive activation to be converted to a bis-electrophile that forms several covalent adducts with DNA, including an interstrand cross-link which is considered to be the lesion responsible for the cytotoxic effects of the drug. Enzymes such as cytochrome...

journal_title：Chemical research in toxicology

authors： Paz MM

更新日期：2009-10-01 00:00:00

abstract：:It is well-known that aromatic diamino-, dihydroxy-, and amino-hydroxy compounds, with NH(2) and OH groups in ortho- or para-positions relative to each other, are strong skin sensitizers. In this paper, we analyze published potency and cross-reactivity data, whereby animals sensitized to one of these compounds are cha...

journal_title：Chemical research in toxicology

authors： Aptula AO,Enoch SJ,Roberts DW

更新日期：2009-09-01 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

authors： Barshteyn N,Elfarra AA

更新日期：2009-09-01 00:00:00

abstract：:Idiosyncratic drug reactions (IDRs) represent a major clinical problem, and at present, the mechanisms involved are still poorly understood. One animal model that we have used for mechanistic studies of IDRs is penicillamine-induced autoimmunity in Brown Norway (BN) rats. Previous work in our lab found that macrophage...

journal_title：Chemical research in toxicology

authors： Li J,Mannargudi B,Uetrecht JP

更新日期：2009-07-01 00:00:00

abstract：:Enzymatic methylation of cytosine residues in DNA, in conjunction with covalent histone modifications, establishes an epigenetic code essential for the proper control of gene expression in higher organisms. Once established during cellular differentiation, the epigenetic code must be faithfully transmitted to progeny ...

journal_title：Chemical research in toxicology

authors： Herring JL,Rogstad DK,Sowers LC

更新日期：2009-06-01 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

authors： Gonçalves LL,Ramkissoon A,Wells PG

更新日期：2009-05-01 00:00:00

abstract：:The toxicity of the ubiquitous pollutant and endogenous metabolite, acrolein, is due in part to covalent protein modifications. Acrolein reacts readily with protein nucleophiles via Michael addition and Schiff base formation. Potential acrolein targets in protein include the nucleophilic side chains of cysteine, histi...

journal_title：Chemical research in toxicology

authors： Cai J,Bhatnagar A,Pierce WM Jr

更新日期：2009-04-01 00:00:00

abstract：:Metabolic bioactivation, glutathione depletion, and covalent binding are the early hallmark events after acetaminophen (APAP) overdose. However, the subsequent metabolic consequences contributing to APAP-induced hepatic necrosis and apoptosis have not been fully elucidated. In this study, serum metabolomes of control ...

journal_title：Chemical research in toxicology

authors： Chen C,Krausz KW,Shah YM,Idle JR,Gonzalez FJ

更新日期：2009-04-01 00:00:00

abstract：:2,3-dimethoxy-1,4-naphthoquinone (CAS-RN 6959-96-3) (DMNQ) and 2-methyl-1,4-naphthoquinone (CAS-RN 58-27-5) (MNQ:menadione) are effective one electron redox cycling chemicals in vitro. In addition, in vitro MNQ forms a thioether conjugate with glutathione by nucleophilic attack at the third carbon. In contrast, here w...

journal_title：Chemical research in toxicology

authors： Parry JD,Pointon AV,Lutz U,Teichert F,Charlwood JK,Chan PH,Athersuch TJ,Taylor EL,Singh R,Luo J,Phillips KM,Vetillard A,Lyon JJ,Keun HC,Lutz WK,Gant TW

更新日期：2009-04-01 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

authors： Jiang Y,Wang Y,Wang Y

更新日期：2009-03-16 00:00:00

abstract：:Guidance from the Food and Drug Administration on drug interaction studies does not include a specific section on contributions of metabolites to observed inhibitory drug-drug interactions, and the quantitative role of drug metabolites in inhibitory drug-drug interactions is not presently known. The current work was u...

journal_title：Chemical research in toxicology

authors： Isoherranen N,Hachad H,Yeung CK,Levy RH

更新日期：2009-02-01 00:00:00

abstract：:Nuclear magnetic resonance (NMR) spectroscopy has traditionally been considered as an indispensable tool in elucidating structures of metabolites. With the advent of Fourier transform (FT) spectrometers, along with improvements in software and hardware (such as high-field magnets, cryoprobes, versatile pulse sequences...

journal_title：Chemical research in toxicology

authors： Espina R,Yu L,Wang J,Tong Z,Vashishtha S,Talaat R,Scatina J,Mutlib A

更新日期：2009-02-01 00:00:00

abstract：:The recent guidance on "Safety Testing of Drug Metabolites" issued by the U.S. Food and Drug Administration, Center for Drug Evaluation and Research (CDER) has highlighted the importance of identifying and characterizing drug metabolites as early as possible in drug discovery and development. Furthermore, upon identif...

journal_title：Chemical research in toxicology

authors： Vishwanathan K,Babalola K,Wang J,Espina R,Yu L,Adedoyin A,Talaat R,Mutlib A,Scatina J

更新日期：2009-02-01 00:00:00

abstract：:The clinical use of the immunosuppressant calcineurin inhibitor cyclosporine is limited by its nephrotoxicity. This is enhanced when combined with the immunosuppressive mTOR inhibitor sirolimus. Nephrotoxicity of both drugs is not yet fully understood. The goal was to gain more detailed mechanistic insights into the t...

journal_title：Chemical research in toxicology

authors： Klawitter J,Bendrick-Peart J,Rudolph B,Beckey V,Klawitter J,Haschke M,Rivard C,Chan L,Leibfritz D,Christians U,Schmitz V

更新日期：2009-01-01 00:00:00

abstract：:Lumiracoxib (Prexige; 2-[(2-fluoro-6-chlorophenyl)amino]-5-methyl-benzeneacetic acid) is a cyclooxygenase-2 selective inhibitor for the symptomatic treatment of osteoarthritis. Recently, the drug has been withdrawn in several countries due to serious liver side effects. Li et al. recently have shown that lumiracoxib i...

journal_title：Chemical research in toxicology

authors： Kang P,Dalvie D,Smith E,Renner M

更新日期：2009-01-01 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

authors： Dalvie D,Kang P,Zientek M,Xiang C,Zhou S,Obach RS

更新日期：2008-12-01 00:00:00

abstract：:Notopterygium forbesii Boiss (NF) has been used as a traditional Chinese medicine for the treatment of common cold and rheumatism. However, there has been limited research on the biological properties of NF, and the mechanisms of action remain unknown. Here, we aimed to study the mechanism of NF-induced heme oxygenase...

journal_title：Chemical research in toxicology

authors： Tang SY,Wang H,Zhang W,Halliwell B

更新日期：2008-12-01 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

authors： Yagi H,Frank H,Seidel A,Jerina DM

更新日期：2008-12-01 00:00:00