Abstract:
:The gender differences in the in vitro microsomal metabolic activation of hepatotoxic clivorine, a representative naturally occurring hepatotoxic otonecine type pyrrolizidine alkaloid, in Sprague-Dawley rats and their relation to the gender differences in susceptibility to clivorine intoxication were reported in the present study. Clivorine-induced liver damage in the male rat via metabolic activation to form the reactive pyrrolic ester followed by covalent binding to liver tissue constituents has been reported previously by our research group. The present study demonstrated, for the first time, that cytochromes p450 3A1 and 3A2, which are constitutively expressed in the male rat, might play a significant role in the metabolic activation of clivorine in the rat. Thus, in the male rat, the metabolic activation by liver microsomes to form the reactive pyrrolic ester was found as the only direct metabolic pathway of clivorine followed by subsequent formation of the toxic tissue-bound pyrroles leading to hepatotoxicity. In the case of the female rat, a less significant metabolic activation was observed, whereas the formations of two novel nonpyrrolic metabolites were determined as the predominant biotransformations. None of the four cDNA-expressed rat enzymes (cytochrome p450 2C12, 2E1, 3A1, 3A2) tested could catalyze the formation of these two new metabolites. Furthermore, the female rat (LD(50) = 114 +/- 9 mg/kg, i.p.) was found to be significantly less susceptible to clivorine intoxication than the male rat (LD(50) = 91 +/- 3 mg/kg, i.p.). Therefore, the results suggested that a significantly lower metabolic activation due to the lack of cytochrome p450 3A1 and p450 3A2 activities mainly accounted for the smaller susceptibility of the female rat to clivorine intoxication.
journal_name
Chem Res Toxicoljournal_title
Chemical research in toxicologyauthors
Lin G,Cui YY,Liu XQdoi
10.1021/tx0340302subject
Has Abstractpub_date
2003-06-01 00:00:00pages
768-74issue
6eissn
0893-228Xissn
1520-5010journal_volume
16pub_type
杂志文章abstract::Prolonged exposure to estrogens correlates with an increased risk for breast cancer. One explanation is that estrogen metabolites cause mutations by reacting with DNA, leading to depurination. We describe an extraction procedure and a liquid chromatographic tandem mass spectrometric (LC/MS/MS) assay to detect estrone-...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx8001737
更新日期:2008-08-01 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
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.8b00286
更新日期:2019-04-15 00:00:00
abstract::Methylmercury (MeHg) reacts readily with GSH, leading to the formation of a MeHg-SG adduct that is excreted into extracellular space through multidrug-resistance-associated protein (MRP), which is regulated by the transcription factor Nrf2. We previously reported that MeHg covalently modifies Keap1 and activates Nrf2 ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx5002332
更新日期:2014-10-20 00:00:00
abstract::The development of a unique bioassay for cytotoxicity analysis of coal fly ash (CFA) particulate matter (PM) and its potential application for air quality monitoring is described. Using human cell lines, A549 and SK-MES-1, as live probes on microelectrode-embedded 96-well sensors, impedance changes over time are measu...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.6b00004
更新日期:2016-06-20 00:00:00
abstract::Atrazine (ATR) is extensively used worldwide as an herbicide, with a global ecological influence. The widespread distribution of herbicides may be one of the possible reasons for the decline in the global amphibian population. The acute toxicity and potential toxicological mechanisms of ATR on the immune system of fro...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.5b00238
更新日期:2015-10-19 00:00:00
abstract::Water samples from the Waka River, which runs through an area housing many chemical industry facilities in Wakayama, Japan, have been found to show significant mutagenicity, especially without a mammalian metabolic activation system (S9 mix) in the Salmonella typhimurium YG1024 strain. Mutagens in the river water were...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx010163g
更新日期:2002-03-01 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::Human hepatocellular carcinoma cells, HepG2, are often used for drug mediated mitochondrial toxicity assessments. Glucose in HepG2 culture media is replaced by galactose to reveal drug-induced mitochondrial toxicity as a marked shift of drug IC50 values for the reduction of cellular ATP. It has been postulated that ga...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.9b00033
更新日期:2019-08-19 00:00:00
abstract::The synthesis of the 8 possible stereoisomeric diol epoxides (DEs) at the terminal benzo ring of carcinogenic dibenz[a,h]anthracene (DBA) is reported. trans-3,4-Dihydroxy-3,4-dihydro-DBA (1) afforded the 4 bay region DEs: the enantiomeric pairs of the anti diastereomers (+)-3/(-)-3 and of the syn diastereomers (-)-4/(...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx200398b
更新日期:2011-12-19 00:00:00
abstract::Many cyanobacterial species are able to produce cyanotoxins as secondary metabolites. Among them, microcystins (MC) are a group of around 80 congeners of toxic cyclic heptapeptides. MC-LR is the most studied MC congener, in view of its high acute hepatotoxicity and tumor promoting activity. Humans may be exposed to cy...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx2000976
更新日期:2011-06-20 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::Capillary liquid chromatography-continuous-flow fast atom bombardment mass spectrometry is applied to the detection of deoxynucleoside adducts of N-acetoxy-N-acetyl-2-aminofluorene. In such a configuration, normal scan and tandem mass spectrometric techniques are shown to provide useful structural information for an N...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00037a013
更新日期:1994-01-01 00:00:00
abstract::To obtain definitive information about the mechanisms of urinary calculus formation and the structural characteristics of the calculi induced by biphenyl administration in rats, with a focus on the sex dependency, the constituents of the urinary calculi were analyzed by HPLC, inductively coupled plasma spectroscopy (I...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx0000163
更新日期:2000-08-01 00:00:00
abstract::The biological response of bronchial epithelial cells to particles is associated with a sequestration of cell metal by the particle surface and a subsequent disruption in host iron homeostasis. The macrophage is the cell type resident in the respiratory tract that is most likely to make initial contact with inhaled pa...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.8b00301
更新日期:2019-09-16 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
pub_type: 杂志文章
doi:10.1021/tx900358j
更新日期:2010-02-15 00:00:00
abstract::Oxidation of the tris(p-carboxyltetrathiaaryl)methyl (TAM) EPR radical probe, TAMa(•), by rat liver microsomes (RLM) + NADPH, or horseradish peroxidase (HRP) + H2O2, or K2IrCl6, led to an intermediate cation, TAMa(+), which was treated with glutathione (GSH), with formation of an adduct, TAMa-SG(•), resulting from the...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx400467p
更新日期:2014-04-21 00:00:00
abstract::Oxidative stress is a commonly cited mechanism of toxicity of environmental agents. Ubiquitous environmental chemicals such as the diesel exhaust component 1,2-naphthoquinone (1,2-NQ) induce oxidative stress by redox cycling, which generates hydrogen peroxide (H2O2). Cysteinyl thiolate residues on regulatory proteins ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.5b00424
更新日期:2015-12-21 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
pub_type: 杂志文章
doi:10.1021/tx800464q
更新日期:2009-04-01 00:00:00
abstract::Inhalation of environmental particulate matter (PM) is correlated with adverse health effects in humans, but gene products that couple detection with cellular responses, and the specific properties of PM that target different pathways, have not been fully elucidated. TRPA1 and V1 are two cation channels expressed by s...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx200123z
更新日期:2011-06-20 00:00:00
abstract::Electronic cigarette liquids (e-liquids) with sweetener additives such as sucralose, a synthetic chlorinated disaccharide, are popular among some e-cigarette consumers; sucralose can be added either by the manufacturer or by the consumer. The prevalence of sucralose in commercial e-liquids is not known, nor is the typ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.9b00047
更新日期:2019-06-17 00:00:00
abstract::Bisphenol A (BPA) is used in the production of polycarbonate plastics and epoxy resins for baby bottles, liners of canned food, and many other consumer products. Previously, BPA has been shown to reduce the activity of several antioxidant enzymes, which may contribute to oxidative stress. However, the underlying mecha...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx400036v
更新日期:2013-03-18 00:00:00
abstract::Platinum group metals (PGMs) is a group of metals that include platinum, palladium, rhodium, ruthenium, iridium, and osmium. Occupational respiratory exposure to platinum has been reported since 1945, but studies investigating occupational exposure to palladium, rhodium, ruthenium, iridium, and osmium are scarce. This...
journal_title:Chemical research in toxicology
pub_type: 杂志文章,评审
doi:10.1021/acs.chemrestox.7b00184
更新日期:2017-10-16 00:00:00
abstract::The reaction of the alpha, beta-unsaturated ketones methyl vinyl ketone (MVK) and ethyl vinyl ketone (EVK) with nucleosides and 5'-mononucleotides was studied. The genotoxic activity of MVK and EVK in the SOS Chromotest was investigated. Three different types of adducts with deoxyguanosine were found and their structu...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00019a007
更新日期:1991-01-01 00:00:00
abstract::Thioureas are oxygenated by flavin-containing monooxygenases (FMOs), forming reactive sulfenic and/or sulfinic acids. Sulfenic acids can reversibly react with GSH and drive oxidative stress through a redox cycle. For this reason, thiourea S-oxygenation is an example of FMO-dependent bioactivation of a xenobiotic. Func...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx034253s
更新日期:2004-05-01 00:00:00
abstract::Oxidative stress is believed to play a role in the pathogenesis of several diseases, including diabetes and inborn errors of metabolism. The types of oxidative damage observed in these pathologies have been attributed to the excessive production of reactive intermediates relating to the accumulation of toxic metabolit...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx049821y
更新日期:2004-12-01 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::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::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 c...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx950123a
更新日期:1996-01-01 00:00:00
abstract::Pesticide biotransformation, especially by cytochrome P450 enzymes (CYPs), may produce metabolites with substantially altered toxicological and physicochemical profiles, which has drawn great attention as a basis for environmental risk assessment. CYPs are active in the metabolism of various reactions of pesticides, a...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.0c00013
更新日期:2020-06-15 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
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.8b00194
更新日期:2018-11-19 00:00:00