Abstract：
:The dosage-regimen-dependent teratogenicity as well as plasma and tissue levels of the antiepileptic drug valproic acid (VPA) were studied in the mouse by comparing various injection regimens and infusion of the drug via implanted osmotic minipumps. Concentrations of 225-248 micrograms VPA/ml maternal plasma (about 2X above the therapeutic concentration range) and 70-75 micrograms VPA/g gestational material (on gestation Day 8) resulted in a significant incidence of neural tube defects (exencephaly in the mouse). Similar effects were produced if those concentrations were reached several times after multiple injections or by steady-state application via implanted pumps. A single injection was less effective than multiple injections, although drug accumulation did not occur. The doses (or area under the concentration-time curve values) did not correlate with the teratogenic response of the different administration regimens: much higher (factor 10) doses were needed with the infusion regimen to produce exencephaly rates comparable to those obtained with the injection regimen. The pattern of embryotoxicity was also schedule dependent: steady-state concentrations produced predominantly embryolethality and fetal weight retardation, while intermittent injections produced a high incidence of exencephaly (up to 60% of live fetuses). The dose of VPA (and the areas under the concentration-time curves) correlated with the embryolethality and fetal weight retardation of the drug, while the peak or steady-state concentrations reached in mother and gestational material correlated with the incidence of neural tube defects.
journal_name
Toxicol Appl Pharmacoljournal_title
Toxicology and applied pharmacologyauthors
Nau Hdoi
10.1016/0041-008x(85)90081-xsubject
Has Abstractpub_date
1985-09-15 00:00:00pages
243-50issue
2eissn
0041-008Xissn
1096-0333pii
0041-008X(85)90081-Xjournal_volume
80pub_type
杂志文章abstract：:Isolated rat lymphocytes in salts-glucose medium (pH 7.2) were incubated with nickel chloride, nickel acetate, nickel sulfate, and a soluble form of nickel subsulfide (0-2 mM) at 37 degrees C for 2 h. The soluble form of nickel subsulfide induced a significant increase in DNA-protein crosslinks (DPXLs) (111%) beginnin...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1006/taap.2000.9097
更新日期：2001-02-01 00:00:00
abstract：:Laboratory studies have described the carcinogenicity of fumonisin B1 (FB1) in rodents and epidemiological evidence suggests an association between FB1 (a mycotoxin produced by Fusarium moniliforme) and cancer in humans. This study was designed to reveal in rainbow trout, a species with very low spontaneous tumor inci...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1006/taap.2001.9129
更新日期：2001-04-01 00:00:00
abstract：:Esophageal squamous cell carcinoma (SCC) is responsible for approximately one-sixth of all cancer-related mortality worldwide. This malignancy has a multifactorial etiology involving several environmental, dietary and genetic factors. Since esophageal cancer has often metastasized at the time of diagnosis, current tre...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.taap.2007.01.030
更新日期：2007-11-01 00:00:00
abstract：:The inter-relationship of "Thresholds" between chemical mixtures and their respective component single chemicals was studied using three sets of data and two types of analyses. Two in vitro data sets involve cytotoxicity in human keratinocytes from treatment of metals and a metal mixture [Bae, D.S., Gennings, C., Cart...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.taap.2006.11.016
更新日期：2007-09-01 00:00:00
abstract：:In the metabolism of isosorbide dinitrate (ISDN), fast denitration with the formation of nitrite ions and a mononitrate plays an important role. In contrast, the denitration of isosorbide-5-mononitrate (IS-5-MN) to isosorbide is very slow. Accordingly po administration of high doses of ISDN (92.5 and 236 mg/kg) in con...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(84)90258-8
更新日期：1984-01-01 00:00:00
abstract：:1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxin is a chemical inducer of Parkinson's disease (PD) whereas N-methylated beta-carbolines and isoquinolines are naturally occurring analogues of MPTP involved in PD. This research has studied the oxidation of MPTP by human CYP2D6 (CYP2D6*1 and CYP2D6*10 allel...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2006.06.003
更新日期：2006-11-01 00:00:00
abstract：:Propanil, 3,4-dichloropropionanilide, a commonly used herbicide, has been shown to induce effects on the mouse immune system. The aim of this study was to assess the immunotoxicity of propanil in occupationally exposed agricultural workers and to characterize its molecular mechanism of action. Seven agricultural worke...
journal_title：Toxicology and applied pharmacology
pub_type： 临床试验,杂志文章
doi：10.1016/j.taap.2007.04.017
更新日期：2007-07-15 00:00:00
abstract：:The effects of the chemical species and concentration of selenium (Se) in diets on the concentrations of Se in hair, blood serum, red blood cells (RBCs), and urine were studied to gain an insight into the toxicological and nutritional significance of different chemical forms of Se. Male Wistar rats were fed an Se-defi...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1006/taap.1998.8537
更新日期：1998-10-01 00:00:00
abstract：:Immobilization of nanoparticles on inorganic supports has been recently developed, resulting in the creation of nanocomposites. Concerning titanium dioxide nanoparticles (TiO2 NPs1), these have already been developed in conjugation with clays, but so far there are no available toxicological studies on these nanocompos...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2016.12.018
更新日期：2017-02-01 00:00:00
abstract：:Occupational exposure to low molecular weight chemicals, like trimellitic anhydride (TMA), can result in occupational asthma. Alveolar macrophages (AMs) are among the first cells to encounter inhaled compounds. These cells can produce many different mediators that have a putative role in asthma. In this study, we exam...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2005.05.012
更新日期：2006-02-15 00:00:00
abstract：:To evaluate the functional significance of bis(tri-n-butyltin)oxide (TBTO)-induced thymus atrophy, lymphocyte depletion in spleen and lymph nodes, lymphopenia, and increased serum IgM and decreased IgG concentrations, in vivo and in vitro function studies were performed for specific and nonspecific resistance. Weaned ...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(84)90177-7
更新日期：1984-09-30 00:00:00
abstract：:Recently, we described a family of non-targeting monomethylauristatin E (MMAE) antibody-drug conjugates (ADCs) whose pharmacokinetics could be tuned through incorporation of a short polyethylene glycol (PEG) moiety of up to twelve units into a drug-linker to render the ADC surface more hydrophilic. That work demonstra...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2020.114932
更新日期：2020-04-01 00:00:00
abstract：:Environmental risk assessment requires models for estimating the bioaccumulation of untested compounds. So far, bioaccumulation models have focused on lipophilic compounds, and only a few have included hydrophilic compounds. Our aim was to extend an existing bioaccumulation model to estimate the oral uptake efficiency...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2012.10.015
更新日期：2013-01-01 00:00:00
abstract：:The multidrug resistance (MDR) transporter is a phosphorylated glycoprotein (P-gp) that has been implicated in the efflux of a large variety of xenobiotics, thereby protecting vital organs. This study examines the hypothesis that the multidrug resistance transporter is involved in restricting the entry of polychlorina...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/s0041-008x(02)00069-8
更新日期：2003-03-15 00:00:00
abstract：:Juvenile rat toxicity studies with the direct renin inhibitor aliskiren were initiated to support treatment in the pediatric population. In Study 1, aliskiren was administered orally to juvenile rats at doses of 0, 30, 100 or 300 mg/kg/day with repeated dosing from postpartum day (PPD) 8 to PPD 35/36. In-life, clinica...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2013.12.019
更新日期：2014-02-15 00:00:00
abstract：:Ghrelin is a 28-amino-acid peptide that acts as a natural endogenous ligand of the growth hormone secretagogue receptor (GHSR) and strongly stimulates the release of growth hormone from the hypothalamus-pituitary axis. Previous studies have identified the important physiological effects of ghrelin on bone metabolism, ...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2013.07.018
更新日期：2013-11-01 00:00:00
abstract：:The present studies were designed to evaluate the role that metabolic activation plays in allylamine (AAM)-induced vascular toxicity. The effects of AAM were evaluated in primary cultures of rat vascular endothelial (VEC) and smooth muscle cells (SMC). Semicarbazide (SC) and diethyldithiocarbamate (DDC) were used as i...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/s0041-008x(88)80008-5
更新日期：1988-08-01 00:00:00
abstract：:Tabun represents the phosphoramidate class of organophosphates that are covalent inhibitors of acetylcholinesterase (AChE), an essential enzyme in neurotransmission. Currently used therapy in counteracting excessive cholinergic stimulation consists of a muscarinic antagonist (atropine) and an oxime reactivator of inhi...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2019.04.007
更新日期：2019-06-01 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：:The substrate preference of an aldehyde dehydrogenase induced in rat liver cytosol by 3-methylcholanthrene was examined. This enzyme, T-ALDH, is identical to the aldehyde dehydrogenase inducible in rat liver by 2,3,7,8-tetrachloro-dibenzo-p-dioxin and the tumor-associated aldehyde dehydrogenase found in rat hepatocell...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(88)90170-6
更新日期：1988-09-15 00:00:00
abstract：:Eupafolin, a major active component found in the methanol extracts of Phyla nodiflora, has been used to treat inflammation of skin. We examined its effects on cyclooxygenase-2 (COX-2) expression in LPS-treated human dermal fibroblasts. Lipopolysaccharide (LPS) significantly increased prostaglandin-E2 (PGE2) production...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2014.06.012
更新日期：2014-09-01 00:00:00
abstract：:Organophosphorus esters (OP) are highly toxic chemicals used as pesticides and nerve agents. Their acute toxicity is attributed to inhibition of acetylcholinesterase (AChE, EC 3.1.1.7) in nerve synapses. Our goal was to find a new therapeutic for protection against OP toxicity. We used a gene therapy vector, adeno-ass...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2005.12.008
更新日期：2006-07-15 00:00:00
abstract：:Arsenic trioxide (ATO) has been reported to inhibit the activity of Ten-eleven translocation methylcytosine dioxygenase (TET). TET modulates FOXP3 expression, while dysregulation of FOXP3 expression promotes the malignant progression of leukemia cells. We examined the role of TET-FOXP3 axis in the cytotoxic effects of...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2018.09.008
更新日期：2018-11-01 00:00:00
abstract：:An experimental system was chosen to investigate the bioactivity of a lipoprotein-sequestered toxicant at the cellular level based on recent studies demonstrating receptor-mediated uptake of lipoproteins by macrophages. Rat peritoneal exudate cell suspensions (PEC) were exposed to DDT and lipoprotein-sequestered DDT, ...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(86)90282-6
更新日期：1986-03-15 00:00:00
abstract：:The H295R cell bioassay was used to evaluate the potential endocrine disrupting effects of 18 of the most commonly used pharmaceuticals in the United States. Exposures for 48 h with single pharmaceuticals and binary mixtures were conducted; the expression of five steroidogenic genes, 3betaHSD2, CYP11beta1, CYP11beta2,...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2007.07.013
更新日期：2007-12-01 00:00:00
abstract：:Ethanol induces cumulative liver damage including steatosis, steatohepatitis and cirrhosis. The aim of this study is to investigate the global intrahepatic gene expression profile in the mouse liver treated with ethanol. A single oral dose of 0.5 or 5 g/kg ethanol was administered to male ICR mice, and liver samples w...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2007.06.018
更新日期：2007-09-15 00:00:00
abstract：:Daily subcutaneous administration of 20 or 100 mg/kg gentamicin for 4 days significantly decreased pyridoxal-5'-phosphate and lysosomal specific phosphatidylinositol-phospholipase C (PI-PLC) in newborn rat kidney. The fall in PI-PLC was associated with an elevation in renal phosphatidylinositol, phosphatidylserine, an...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(89)90111-7
更新日期：1989-06-01 00:00:00
abstract：:Dimethyl sulfoxide (DMSO) can protect the liver from injury produced by a variety of hepatotoxicants when administered prior to or concomitant with the toxicants. This protective action has previously been attributed to DMSO-induced inhibition of bioactivation of the compounds to toxic intermediates. In these studies,...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1006/taap.1996.8009
更新日期：1997-01-01 00:00:00
abstract：:Nickel (Ni) carcinogenesis is thought to involve gene chip silencing by epigenetic mechanisms. Serpina3g, a member of the mouse serpin family, was among the most down-regulated genes (32-fold) in response to Ni exposure of mouse cells based on the Affymetrix gene chip. Serpina3g down-regulation was controlled by a hyp...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2003.08.011
更新日期：2004-01-01 00:00:00
abstract：:In this study, the effects of pentavalent dimethylarsinic acid ((CH(3))(2)AsO(OH); DMA(V)) and trivalent dimethylarsinous acid ((CH(3))(2)As(OH); DMA(III)) on synaptic transmission generated by the excitatory Schaffer collateral-CA1 synapse were tested in hippocampal slices of young (14-21 day-old) and adult (2-4 mont...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2007.07.007
更新日期：2007-11-15 00:00:00
