Bioactivation of lumiracoxib by peroxidases and human liver microsomes: identification of multiple quinone imine intermediates and GSH adducts.

abstract：:Idiosyncratic adverse drug reactions due to the anti-inflammatory drug diclofenac have been proposed to be caused by the generation of reactive acyl glucuronides and oxidative metabolites. For the oxidative metabolism of diclofenac by cytochromes P450 at least five different reactive intermediates have been proposed p...

journal_title：Chemical research in toxicology

authors： Dragovic S,Boerma JS,Vermeulen NP,Commandeur JN

更新日期：2013-11-18 00:00:00

abstract：:Paraquat (PQ) is a free radical-inducing agent commonly used as an herbicide. This study assesses the acute immunotoxicity of PQ in BALB/c mice and examines its effect on cytokine gene expression profile. It was found that single subtoxic oral doses of 2, 4, and 20 mg/kg significantly inhibited the in vitro mitogen-in...

journal_title：Chemical research in toxicology

authors： Hassuneh MR,Albini MA,Talib WH

更新日期：2012-10-15 00:00:00

abstract：:The tumorigenic activity of manufactured gas plant residue (MGP) was evaluated in female A/J mice using a F0927 basal gel diet system. Adulterated diets containing MGP (0.10% or 0.25%) or benzo[a]pyrene (B[alpha]P; 16 or 98 ppm) were fed for 260 days. A negative control group was maintained on a nonadulterated basal g...

journal_title：Chemical research in toxicology

authors： Weyand EH,Chen YC,Wu Y,Koganti A,Dunsford HA,Rodriguez LV

更新日期：1995-10-01 00:00:00

abstract：:Zileuton, an inhibitor of 5-lipooxygenase, the initial enzyme in the leukotriene pathway, was marketed as a new treatment for asthma. This drug has been associated with liver toxicity, which has limited its clinical usefulness. We provide evidence here that the liver toxicity likely involves a sequence of biotransform...

journal_title：Chemical research in toxicology

authors： Joshi EM,Heasley BH,Chordia MD,Macdonald TL

更新日期：2004-02-01 00:00:00

abstract：:DNA molecules utilize adenine, thymine, cytosine, and guanine for coding genetic information. In addition to these four canonical nucleobases, DNA molecules also contain a variety of modified nucleobases that can control and regulate gene expression and chromosome structure. Elucidating the functions of DNA modificati...

journal_title：Chemical research in toxicology

authors： Yuan BF

更新日期：2020-03-16 00:00:00

abstract：:Flucloxacillin, an isoxazolyl-penicillin, causes cholestasis and biliary epithelium injury. The aim of the study was to determine whether flucloxacillin, either directly or through metabolite formation, may induce cytotoxicity in hepatic or biliary cells. Cytotoxicity was assessed by lactate dehydrogenase release in p...

journal_title：Chemical research in toxicology

authors： Lakehal F,Dansette PM,Becquemont L,Lasnier E,Delelo R,Balladur P,Poupon R,Beaune PH,Housset C

更新日期：2001-06-01 00:00:00

abstract：:Thalidomide is an infamous teratogen and it is continuously being explored for its anticancer properties. Fibroblast growth factor receptors (FGFRs) are implicated in embryo development and cancer pathophysiology. With striking similarities observed between FGFR implicated conditions and thalidomide embryopathy, we hy...

journal_title：Chemical research in toxicology

authors： Sundaresan L,Kumar P,Manivannan J,Balaguru UM,Kasiviswanathan D,Veeriah V,Anishetty S,Chatterjee S

更新日期：2019-04-15 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

authors： Watanabe K,Guengerich FP

更新日期：2006-08-01 00:00:00

abstract：:Methyleugenol (ME), an alkenylbenzene compound, is a natural ingredient of several herbs and is used as flavoring agent in foodstuffs and fragrance in cosmetics. The hepatotoxicity, cytotoxicity, and carcinogenesis of ME have been well documented, and metabolic activation has been suggested to involve in ME-induced to...

journal_title：Chemical research in toxicology

authors： Feng Y,Wang H,Wang Q,Huang W,Peng Y,Zheng J

更新日期：2017-02-20 00:00:00

abstract：:Mitomycin C (MC), a cytotoxic anticancer drug and bifunctional DNA DNA alkylating agent, induces cross-linking of the complementary strands of DNA. The DNA interstrand cross-links (ICLs) are thought to be the critical cytotoxic lesions produced by MC. Decarbamoyl mitomycin C (DMC) has been regarded as a monofunctional...

journal_title：Chemical research in toxicology

authors： Palom Y,Suresh Kumar G,Tang LQ,Paz MM,Musser SM,Rockwell S,Tomasz M

更新日期：2002-11-01 00:00:00

abstract：:The rat esophagus is strikingly sensitive to tumor induction by nitrosamines, and it has been hypothesized that this tissue contains cytochrome P450 enzymes (P450s) which catalyze the metabolic activation of these carcinogens. The metabolic capacity of the esophagus is not well characterized. In the study described he...

journal_title：Chemical research in toxicology

authors： von Weymarn LB,Murphy SE

更新日期：2001-10-01 00:00:00

abstract：:Troglitazone (TGZ), a 2,4-thiazolidinedione antidiabetic, causes hepatotoxicity in 1.9% of patients. TGZ is an inducer of, and substrate for, hepatic P450 3A. Microsomal metabolism yields a benzoquinone (TGZQ) and reactive intermediates. Kassahun et al. [Kassahun et al. (2001) Chem. Res. Toxicol. 14, 62-70] have trapp...

journal_title：Chemical research in toxicology

authors： Tettey JN,Maggs JL,Rapeport WG,Pirmohamed M,Park BK

更新日期：2001-08-01 00:00:00

abstract：:The antioxidant properties of a number of water-soluble diorganyl tellurides have been investigated. These organotellurium compounds efficiently protect against peroxynitrite-mediated oxidation of dihydrorhodamine 123, hydroxylation of benzoate, and nitration of 4-hydroxyphenyl acetate. The peroxidation of the zinc st...

journal_title：Chemical research in toxicology

authors： Jacob C,Arteel GE,Kanda T,Engman L,Sies H

更新日期：2000-01-01 00:00:00

abstract：:4-Hydroxy-2-nonenal (HNE), a major electrophilic byproduct of lipid peroxidation, is mutagenic and cytotoxic. The two pairs of HNE-derived diastereomeric 1,N2-propanodeoxyguanosine 3'-monophosphate adducts were synthesized from reaction of HNE with 2'-deoxyguanosine 3'-monophosphate. After HPLC separation, these adduc...

journal_title：Chemical research in toxicology

authors： Yi P,Zhan D,Samokyszyn VM,Doerge DR,Fu PP

更新日期：1997-11-01 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

authors： Sanchez AM,Minko IG,Kurtz AJ,Kanuri M,Moriya M,Lloyd RS

更新日期：2003-08-01 00:00:00

abstract：:Cyadox is a novel derivative of quinoxaline-1,4-dioxides (QdNOs) with the potential to be developed as a feed additive. However, the pharmacological and toxicological bioactive molecules of cyadox and the molecular mechanism of its pharmacological and toxic actions remain unclear. In the present study, cyadox and its ...

journal_title：Chemical research in toxicology

authors： Liu Q,Lei Z,Zhou K,Yu H,Liu S,Sun Q,Wang X,Dai M,Yuan Z

更新日期：2018-11-19 00:00:00

abstract：:Among the cellular components that can react directly with peroxynitrite in the presence of physiological CO(2) concentrations are sulfur-, selenium-, and metal-containing proteins, in particular hemoproteins. We have previously shown that the reactions of peroxynitrite with oxymyoglobin (MbFeO(2)) and oxyhemoglobin p...

journal_title：Chemical research in toxicology

authors： Herold S,Exner M,Boccini F

更新日期：2003-03-01 00:00:00

abstract：:Aryl radicals can react at the C8-site of 2'-deoxyguanosine (dG) to produce DNA adducts with a C8-C linkage (denoted C-linked). Such adducts are structurally distinct from those possessing a flexible amine (N-linked) or ether (O-linked) linkage, which separates the C8-aryl moiety from the guanine nucleobase. In the cu...

journal_title：Chemical research in toxicology

authors： Sproviero M,Verwey AM,Witham AA,Manderville RA,Sharma P,Wetmore SD

更新日期：2015-08-17 00:00:00

abstract：:Peroxynitrite (PN), a very reactive oxidant formed by the combination of superoxide and nitric oxide, appears to play a role in producing tissue damage in a number of inflammatory conditions. Pharmacological scavenging and decomposition of PN within these areas has therapeutic value in several tissue injury models. Re...

journal_title：Chemical research in toxicology

authors： Carroll RT,Galatsis P,Borosky S,Kopec KK,Kumar V,Althaus JS,Hall ED

更新日期：2000-04-01 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

authors： Watson WP,Munter T,Golding BT

更新日期：2004-12-01 00:00:00

abstract：:The N-reduction of the centrally acting alpha 2-adrenoreceptor agonist guanoxabenz (Benzérial), an N-hydroxyamidinohydrazone, to the amidinohydrazone guanabenz (Wytensin, Hipten, Rexitene) by microsomal fractions from rabbits, pigs and humans has been detected in vitro. The conversion rates with rabbit microsomal frac...

journal_title：Chemical research in toxicology

authors： Clement B,Demesmaeker M,Linne S

更新日期：1996-06-01 00:00:00

abstract：:Exposure of individual histone proteins (H1, H2A, H2B, H3, or H4) and histone octamers (consisting of two molecules each of H2A, H2B, H3, and H4) to hydroxyl radicals, generated by gamma-irradiation, in the presence of O(2) generates protein-bound hydroperoxides in a dose-dependent fashion; this is in accord with prev...

journal_title：Chemical research in toxicology

authors： Luxford C,Dean RT,Davies MJ

更新日期：2000-07-01 00:00:00

abstract：:A diverse series of aliphatic alpha,beta-unsaturated esters, ketones, and aldehydes were evaluated for reactivity with the model nucleophile sulfhydryl group in the form of the cysteine residue of the tripeptide glutathione; the reactive end point (RC50) was then related to aquatic toxicity (IGC50) assessed in the Tet...

journal_title：Chemical research in toxicology

authors： Yarbrough JW,Schultz TW

更新日期：2007-03-01 00:00:00

abstract：:The hepatic metabolism of microcystins (MCs), potent cyclic peptide hepatotoxins produced by cyanobacteria, was studied by i.p. injection in mice and rats. An immunoaffinity purification method using an anti-MC-LR monoclonal antibody showed a remarkable effect on the removal of contaminants in the hepatic cytosol and ...

journal_title：Chemical research in toxicology

authors： Kondo F,Matsumoto H,Yamada S,Ishikawa N,Ito E,Nagata S,Ueno Y,Suzuki M,Harada K

更新日期：1996-12-01 00:00:00

abstract：:meso-2,3-Dimercaptosuccinic acid is an orally active chelating agent useful for the treatment of lead intoxication. Since it is believed to be extracellular in its distribution, analogs have been synthesized in a search for one that will enter the cell and successfully complete for firmly bound intracellular toxic hea...

journal_title：Chemical research in toxicology

authors： Aposhian HV,Levine DJ,Rivera M,Fernando Q

更新日期：1993-03-01 00:00:00

abstract：:Two samples of highly pure multiwalled carbon nanotubes (MWCNTs) similar in hydrophobicity and surface reactivity were prepared with similar length, <5 μm, but markedly different diameter (9.4 vs 70 nm). The samples were compared for their cytotoxic activity, uptake, and ability to induce oxidative stress (ROS product...

journal_title：Chemical research in toxicology

authors： Fenoglio I,Aldieri E,Gazzano E,Cesano F,Colonna M,Scarano D,Mazzucco G,Attanasio A,Yakoub Y,Lison D,Fubini B

更新日期：2012-01-13 00:00:00

abstract：:This work reveals a novel mechanism for triplet carbonyl formation (and hence chemiluminescence) during lipid peroxidation, whose chemiluminescence has been attributed to both triplet carbonyls and singlet oxygen. As a model for polyunsaturated fatty acid hydroperoxides, we have synthesized 3-hydroperoxy-2,3-dimethyl-...

journal_title：Chemical research in toxicology

authors： Tímmins GS,dos Santos RE,Whitwood AC,Catalani LH,Di Mascio P,Gilbert BC,Bechara EJ

更新日期：1997-10-01 00:00:00

abstract：:With CO2 present in excess, ONOO- reacts to form an adduct in solution and in the solid state, most likely ONOOCO2-. In solution, the adduct appears within 2 ms and absorbs at 300 with an extinction coefficient, which is either 50% or 100% (preferred) of that of ONOO-, 1.70 × 103 M-1 cm-1, and at 685 nm with an extinc...

journal_title：Chemical research in toxicology

authors： Serrano-Luginbuehl S,Kissner R,Koppenol WH

更新日期：2018-08-20 00:00:00

abstract：:Smoked cigarettes are the most prevalent form of litter worldwide, often finding their way into oceans and inland waterways. Cigarette smoke contains more than 4000 individual chemicals, some of them carcinogenic or otherwise toxic. We examined the cytotoxicity, genotoxicity, aryl hydrocarbon receptor (AhR), estrogen ...

journal_title：Chemical research in toxicology

authors： Xu EG,Richardot WH,Li S,Buruaem L,Wei HH,Dodder NG,Schick SF,Novotny T,Schlenk D,Gersberg RM,Hoh E

更新日期：2019-08-19 00:00:00

abstract：:Acrolein is a highly toxic environmental pollutant that readily alkylates the epsilon-amino group of lysine residues in proteins. In model systems, such chemistry involves sequential addition of two acrolein molecules to a given nitrogen, forming bis-Michael-adducted species that undergo aldol condensation and dehydra...

journal_title：Chemical research in toxicology

authors： Kaminskas LM,Pyke SM,Burcham PC

更新日期：2005-11-01 00:00:00