Abstract:
:Vinyl carbamate epoxide (VCO) is believed to be the metabolite of ethyl carbamate (EC) ultimately responsible for its carcinogenic effects. This study investigates the role of glutathione (GSH) in protection against VCO-mediated adduct formation, and the involvement of glutathione S-transferases (GSTs) in detoxification of VCO. Formation of 1,N6-ethenoadenosine from VCO and adenosine in vitro was employed as a measure of VCO toxicity. GSH inhibited formation of ethenoadenosine in a concentration-dependent manner at concentrations ranging from 1 to 8 mM. This effect was significantly enhanced by addition of rat liver GST. Mouse liver cytosol was also found to inhibit formation of ethenoadenosine in a concentration-dependent manner, and the inhibition was relieved by addition of S-octylglutathione, a competitive inhibitor of GST. Pretreatment of mice with 1% dietary (2(3)-tert-butyl-4-hydroxyanisole (BHA) caused parallel increases in cytosolic GST activity and cytosolic enhancement of detoxification of VCO by GSH. Furthermore, BHA increased hepatic steady-state concentrations of GSH greater than twofold. The effect of BHA on detoxification of EC in vivo was examined using formation of 2-oxoethylvaline (OEV) adducts of hemoglobin as a biomarker. Pretreatment with BHA decreased overall formation of OEV adducts 23%. The major conclusions of this study are (1) VCO can be detoxified by spontaneous conjugation with GSH, (2) conjugation of VCO with GST can be catalyzed by GST(s), (3) pretreatment with BHA protects against binding of active EC metabolites in vitro and in vivo, and (4) the protective effect of BHA against EC is mediated by increases in GST activity and GSH concentration.
journal_name
Toxicol Appl Pharmacoljournal_title
Toxicology and applied pharmacologyauthors
Kemper RA,Myers SR,Hurst HEdoi
10.1006/taap.1995.1213subject
Has Abstractpub_date
1995-11-01 00:00:00pages
110-8issue
1eissn
0041-008Xissn
1096-0333pii
S0041-008X(85)71213-6journal_volume
135pub_type
杂志文章abstract::There are conflicting reports in the literature regarding the role of the Ah locus in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) immunotoxicity. The present studies have utilized two congenic strains of C57Bl/6 mice that differ only at this locus to assess its influence on TCDD-induced suppression of antibody response...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(90)90356-y
更新日期:1990-08-01 00:00:00
abstract::A pressing need exists to develop and validate molecular biomarkers to assess the early effects of chemical agents, both individually and in mixtures. This is particularly true for new and chemically intensive industries such as the semiconductor industry. Previous studies from this laboratory and others have demonstr...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2005.01.020
更新日期:2005-08-07 00:00:00
abstract::Prescribing appropriate Tacrolimus (Tac) dosing is still a challenge for clinicians due to the interindividual variability in dose requirement and the narrow therapeutic index. Our objective is to identify potential factors that affects Tac exposure in Tunisian Kidney patients and to develop and validate a Tac dose re...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2020.115245
更新日期:2020-11-15 00:00:00
abstract::Environmental exposure to polychlorinated biphenyls (PCBs) is associated with an increased risk of incidence of metabolic disease, however the molecular mechanisms underlying this phenomenon are not fully understood. Our study provides new insights into molecular interactions between PCBs and retinoids (vitamin A and ...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2019.114731
更新日期:2019-10-15 00:00:00
abstract::In an earlier study, we exposed nine healthy volunteers to known concentrations of mercury (Hg) vapor in air (median 399; range 365-430 micrograms/m3) for 15 min during light physical exercise (50 W) (Sandborgh-Englund, G., et al., Toxicol. Appl. Pharmacol. 150, 146-153, 1998). Exhaled air, urine, and plasma samples w...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1998.8585
更新日期:1999-03-01 00:00:00
abstract::The results of a series of screening tests to determine the potential teratogenicity and neurotoxicity of developmental exposure to TBTO in rats are presented in this paper. For prenatal exposure, pregnant Long Evans rats were intubated with 0-16 mg/kg/day bis(tri-n-butyltin)oxide TBTO from Days 6 to 20 of gestation (...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(89)90060-4
更新日期:1989-01-01 00:00:00
abstract::Previous studies have shown that fumonisin B1 (FB1) inhibits ceramide synthase, resulting in accumulation of free sphinganine and sphingosine. Tumor necrosis factor-alpha (TNFalpha) plays an important role in FB1 toxicity and the expression of TNFalpha mRNA in liver and kidney is increased following FB1 exposure in mi...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.2001.9189
更新日期:2001-07-01 00:00:00
abstract::The high affinity metal-binding protein metallothionein (MT) is thought to detoxify cadmium (Cd) but appears to be deficient in several known targets of Cd carcinogenesis. The rat ventral prostate (VP) was recently identified as one of these target tissues. The nature of the Cd-binding proteins in the prostate has not...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(89)90214-7
更新日期:1989-10-01 00:00:00
abstract::Organic cations (OCs) constitute a diverse array of compounds of physiological, pharmacological, and toxicological importance. Renal secretion of these compounds, which occurs principally along the proximal portion of the nephron, plays a critical role in regulating the concentration of OCs in the plasma and in cleari...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.taap.2004.10.021
更新日期:2005-05-01 00:00:00
abstract::Eicosanoids released after ozone exposure of a human bronchial epithelial cell line, BEAS-S6, were analyzed by high-pressure liquid chromatography (HPLC) of supernatants from exposed cells prelabeled with [3H]arachidonic acid. BEAS cells released thromboxane B2 (TxB2), prostaglandin E2 (PGE2), leukotriene C4 (LTC4), L...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1993.1027
更新日期:1993-02-01 00:00:00
abstract::The differential effects of oral and dermal administration of single doses of 100 to 1000 mg/kg S,S,S-tri-n-butyl phosphorotrithioate (DEF) on nonspecific esterases and liver metabolism enzymes were investigated one day following administration. O,O-Diethyl O-(4-nitrophenyl) phosphorothioate (parathion) and tri-o-cres...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(84)90336-3
更新日期:1984-04-01 00:00:00
abstract::It was investigated whether protective influence of zinc (Zn) against cadmium (Cd)-induced disorders in bone metabolism may be related to its antioxidative properties and impact on the receptor activator of nuclear factor (NF)-κΒ (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) system. Numerous indices of oxidative/an...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2013.05.016
更新日期:2013-10-01 00:00:00
abstract::Endothelial apoptosis is a driving force in atherosclerosis development. Oxidized low-density lipoprotein (oxLDL) promotes inflammatory and thrombotic processes and is highly atherogenic, as it stimulates macrophage cholesterol accumulation and foam cell formation. Previous studies have shown that the phosphatidylinos...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2010.07.025
更新日期:2010-10-15 00:00:00
abstract::Natural flavonoids have diverse pharmacological activities, including anti-oxidative, anti-inflammatory, and anti-cancer activities. In this study, we investigated the molecular mechanism underlying the action of 5-methoxyflavanone (5-MF) which has a strong bioavailability and metabolic stability. Our results show tha...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2011.05.003
更新日期:2011-08-01 00:00:00
abstract::While procedures have been developed and used for many years to assess risk and determine acceptable exposure levels to individual chemicals, most cases of environmental contamination can result in concurrent or sequential exposure to more than one chemical. Toxicological predictions of such combinations must be based...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.taap.2006.07.009
更新日期:2007-09-01 00:00:00
abstract::Clofibric acid (CA), a potent peroxisome proliferator (PP), has been shown to cause tumor formation in rat liver. The precise mechanism of action of PPs remains largely unknown. However, it has been proposed that they act by increasing reactive oxygen species (ROS), leading to a cellular oxidative stress. In the prese...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.2001.9214
更新日期:2001-08-01 00:00:00
abstract::A comparative study was undertaken in order to assess the hematotoxic effects of hydroquinone (HQ), 1,4-benzoquinone (BQ), and doxorubicin (DX) on mouse and human bone marrow (BM) cells. Initial experiments indicated that the inhibitory effects of near-ambient pO2 and HQ on granulocyte/macrophage colony-stimulating fa...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1994.1232
更新日期:1994-11-01 00:00:00
abstract::Risk assessments are enhanced when policy and other decision-makers have access to experimental science designed to specifically inform key policy questions. Currently, our scientific understanding and science policy for environmental mixtures are based largely on extrapolating from and combining data in the observabl...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.taap.2007.02.010
更新日期:2007-09-01 00:00:00
abstract::Aromatase inhibitors like anastrozole play an undisputed key role in the treatment of breast cancer, but on the other hand, various side effects like osteoporosis and increased risk of bone fracture accompany the chronic administration of these drugs. Here we show for the first time that selenium nanoparticles, when g...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2013.01.028
更新日期:2013-04-15 00:00:00
abstract::Dietary consumption of phytoestrogens like genistein has been linked with lower incidence of prostate cancer. The estradiol-like benzopyran core of genistein confers estrogen receptor-β (ER-β) selectivity that imparts weak anti-proliferative activity against prostate cancer cells. DL-2-[4-(2-piperidinoethoxy)phenyl]-3...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2015.01.017
更新日期:2015-03-15 00:00:00
abstract::Ah receptor was identified and characterized in cytosol and nuclear extracts from the rainbow trout hepatoma cell line RTH-149. The cytosolic receptor was detectable with both halogenated ([3H]2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)) and non-halogenated ([3H]3-methylcholanthrene and [3H]benzo[a]pyrene) aromatic hyd...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(90)90105-4
更新日期:1990-10-01 00:00:00
abstract::Zinc oxide (ZnO) particle induced cytotoxicity was dependent on size, charge and solubility, factors which at sublethal concentrations may influence the activation of the human monocytic cell line THP1. ZnO nanoparticles (NP; average diameter 70nm) were more toxic than the bulk form (<44μm mesh) and a positive charge ...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2012.10.020
更新日期:2013-01-01 00:00:00
abstract::The selenoprotein thioredoxin reductase (TXNRD) is a promising therapeutic target for cancer. To discover novel TXNRD inhibitors, a library of α, β-unsaturated carbonyl compounds were applied in structure-based virtual screening for the selection of hit compounds. Fifteen top-ranked compounds were further validated ex...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2019.03.014
更新日期:2019-05-01 00:00:00
abstract::To characterize modes of action of substances and their cytotoxic effects Bionas GmbH has developed a new screening system to allow the continuous recording of how an active substance can act (Bionas 2500 analyzing system). In the pharmaceutical industry it is important to acquire as much information as possible about...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2006.12.027
更新日期:2007-04-01 00:00:00
abstract::The Constitutive Androstane Receptor (CAR, NR1I3) has been newly described as a regulator of energy metabolism. A relevant number of studies using animal models of obesity suggest that CAR activation could be beneficial on the metabolic balance. However, this remains controversial and the underlying mechanisms are sti...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2016.05.006
更新日期:2016-07-15 00:00:00
abstract::Arsenic had been reported to be associated with carotid atherosclerosis. However, there were few studies to evaluate the association between the susceptible gene of lipid metabolism and inflammation and carotid atherosclerosis among arsenic exposure residents. The aim of the study was to investigate the associations b...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2007.10.013
更新日期:2008-02-15 00:00:00
abstract::1,6-Hexamethylene diisocyanate biuret trimer (HDI-BT) is a nonvolatile isocyanate that is a component of polyurethane spray paints. HDI-BT is a potent irritant that when inhaled stimulates sensory nerves of the respiratory tract. The role of sensory nerves in modulating lung injury following inhalation of HDI-BT was a...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2007.06.007
更新日期:2007-10-01 00:00:00
abstract::Staphylococcal enterotoxin C2 (SEC2), a member of bacterial superantigen, is one of the most potent known activators of T lymphocytes. With this property, SEC2 has already been used in clinic as a tumor immunotherapy agent in China. To increase the antitumor activity, a SEC2 mutant named ST-4 (GKVTG102-106WWH) with am...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2016.10.009
更新日期:2016-12-15 00:00:00
abstract::Acute exposure to Cd produces liver injury, whereas chronic exposure results in kidney injury. Tolerance to the hepatotoxicity is observed during chronic exposure to Cd due to the induction of metallothionein (MT). The nephrotoxicity produced by chronic Cd exposure purportedly results from renal uptake of Cd-metalloth...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(88)90231-1
更新日期:1988-01-01 00:00:00
abstract::The relationship of exposure and tissue concentration of parent chemical and metabolites over prolonged exposure is a critical issue for chronic toxicities mediated by metabolite(s) rather than parent chemical alone. This is an issue for AsV because its trivalent metabolites have unique toxicities and relatively great...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2008.07.018
更新日期:2008-11-01 00:00:00