Abstract:
:To investigate mechanisms of chemical-induced congenital heart defects (CHD) we have developed a rat model using dimethadione (DMO), the N-demethylated metabolite of the anticonvulsant, trimethadione (TMD). Dosing pregnant rats with 300mg/kg DMO every 12h from the evening of gestational day (GD) 8 until the morning of GD 11 (six total doses) produces a mean 74% incidence of CHD with inter litter variability ranging from 40 to 100%. The goal of this study was to determine if the variability in maternal serum concentrations of DMO on GD 14, a surrogate marker for total exposure, was related to the inter-litter differences in teratogenic outcomes. To test this hypothesis, pregnant rats were dosed as described above and serum levels of DMO assessed on GD 14. On GD 21, foetuses were collected by caesarean section, assessed for a number endpoints and the outcomes were correlated with the GD 14 serum concentrations of DMO. DMO exposure was associated with decreased foetal body weight, increased incidence of sternal defects and CHD, but these endpoints were not meaningfully correlated with maternal concentrations of DMO. Novel findings were decreased viability as measured one-hour following caesarean section, and delayed alveolar maturation. The major conclusions from these studies were first, that serum DMO concentrations on GD 14 did not predict teratogenicity, and second, delayed lung development may contribute to the decreased survival of foetuses at the time of caesarean section.
journal_name
Toxicologyjournal_title
Toxicologyauthors
Rodger I,Lam I,Purssell E,Thompson M,Rutter A,Ozolinš TRdoi
10.1016/j.tox.2014.10.014subject
Has Abstractpub_date
2014-12-04 00:00:00pages
142-52eissn
0300-483Xissn
1879-3185pii
S0300-483X(14)00210-8journal_volume
326pub_type
杂志文章相关文献
TOXICOLOGY文献大全abstract::The effects of di-(2-ethylhexyl)adipate (DEHA) have been compared in female F344 rats and female B6C3F1 mice fed diets containing 0-4.0% DEHA and 0-2.5% DEHA, respectively, for periods of 1, 4 and 13 weeks. In both the rat and mouse treatment with DEHA at all time points produced a dose-dependent increase in relative ...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/s0300-483x(97)00125-x
更新日期:1997-12-05 00:00:00
abstract::Cisplatin is used as a cytotoxic agent for the management of cervical cancer. However, the severity of the side-effects limits the use of this drug, particularly at high doses. Resistance to cisplatin is often attributed to a disruption in the normal apoptotic response via aberrant activation of pathways such as the m...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2015.07.010
更新日期:2015-09-01 00:00:00
abstract::Young adult male and female Wistar rats were inhalationally exposed head-only for 1 or 4 h to different anticholinesterase aerosols. The compounds tested were dichlorvos, fenamiphos, methamidophos, parathion, a pyrimidine thiophosphate and the carbamate propoxur. These compounds are direct or indirect inhibitors of ch...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(87)90126-0
更新日期:1987-10-30 00:00:00
abstract::In order to test the hypothesis that Leydig cells are required for the acute toxic effect of cadmium on the testis, adult male rats were treated with the Leydig cell toxin ethane dimethanesulphonate (EDS). Four days later, when all Leydig cells are removed from the testis, the EDS treated and control rats were given a...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(90)90041-e
更新日期:1990-08-01 00:00:00
abstract::Although NO2-induced cytotoxic responses have been well characterized, the specific mechanisms responsible for initiating toxicity remain equivocal. The inhomogeneous distribution of epithelial injury suggests that differential interactions between NO2 and the lung surfaces may contribute to the extent of regional res...
journal_title:Toxicology
pub_type: 杂志文章,评审
doi:10.1016/0300-483x(94)90099-x
更新日期:1994-05-20 00:00:00
abstract::In this report the neurotoxicity of aspartame and its constituent amino acids aspartic acid and phenylalanine is reviewed. The adverse reactions ascribed to the consumption of aspartame-containing products, as reported in the U.S.A., are discussed and placed in perspective with the results of recent behavioural studie...
journal_title:Toxicology
pub_type: 杂志文章,评审
doi:10.1016/0300-483x(88)90117-5
更新日期:1988-06-01 00:00:00
abstract::Groups of 15 male and 15 female rats were give 0 (control), 50, 100, 200 or 800 ppm allyl alcohol in the drinking water for 15 weeks. There were no effects attributable to allyl alcohol in the results of the haematological examinations or analyses of serum. There was a dose-related reduction in the fluid intake at all...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(78)90029-x
更新日期:1978-02-01 00:00:00
abstract::Consequences of exposure of rats for 2 days or less to O3 at various concentrations between 0.12 and 0.96 ppm were measured using several assays performed on bronchoalveolar lavage fluid. Changes in apparent lung permeability were assessed by measurement of recovery of labelled bovine serum albumin in lung lavage flui...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(86)90074-0
更新日期:1986-08-01 00:00:00
abstract::We compared the results of the multiple-dose guinea pig maximization test (GPMT) and the non-radioactive murine local lymph-node assay (LLNA) for various biocides. Thirteen out of 17 positive biocides in the GPMT gave positive results in the LLNA. In the GPMT, the minimum first induction doses ranged over four orders ...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2005.02.014
更新日期:2005-07-01 00:00:00
abstract::Inhibition of fungal lanosterol-14 alpha-demethylase (CYP51) is the working principle of the antifungal activity of azoles used in agriculture and medicine. Inhibition of human CYP51 may result in endocrine disruption since follicular fluid-meiosis activating steroid (FF-MAS), the direct product of lanosterol demethyl...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2006.08.007
更新日期:2006-11-10 00:00:00
abstract::Ochratoxin A (OCT A) has the potential to cause myelotoxicity in addition to the well-known toxic effects on the liver and kidney. Whereas in previous studies the bone marrow parameters were examined shortly after injection, experiments reported here were designed to determine whether mice would recover from the myelo...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(88)90236-3
更新日期:1988-12-16 00:00:00
abstract::Transforming growth factor beta (TGF beta) is a multifunctional regulator of cell growth that has either a stimulatory or inhibitory effect on cell proliferation, depending on TGF beta concentration and on cell type, history and culture conditions. Cadmium mimics some of the effects of TGF beta in cultured cells. In t...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(92)90063-k
更新日期:1992-01-01 00:00:00
abstract::The effect of zinc (Zn) on the immunomodulatory properties of cadmium (Cd) was investigated in male Wistar rats. Animals were orally exposed to Cd and or Zn, by stomach tubing for 7 weeks. Response of splenocytes to phytohemagglutinin (PHA) and concanavalin A (Con A), was significantly increased by Zn. When exposed in...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(84)90046-5
更新日期:1984-12-01 00:00:00
abstract::The synthetic pyrethroid insecticide, cypermethrin, was given during gestation to pregnant rats by gavage in corn oil. Peripheral blood and spleen cytotoxic activity of dams and their offspring were then evaluated at different times (30, 60, 90, 120 days) after birth. Pups showed a significant increase in peripheral b...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/s0300-483x(97)03662-7
更新日期:1997-07-11 00:00:00
abstract::Rats were treated with a single dose of thallium acetate (32 mg/kg i.p.) and the antidotal effect of D-penicillamine and prussian blue given alone or in combination was assessed by means of evaluation of the thallium-induced cerebellar histological lesions. After thallium poisoning (24 h), antidotes were administered ...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(94)90129-5
更新日期:1994-03-25 00:00:00
abstract::4-Bromo-2,5-dimethoxyphenethylamine (2C-B) is a psychoactive designer drug of abuse that is sold under the street names "Venus", "Bromo", "Erox", "XTC" or "Nexus". Concern has been raised because only little is known about its toxicity and metabolism in humans. In the present study we incubated 2C-B with human, monkey...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2004.07.004
更新日期:2005-01-05 00:00:00
abstract::The objective of this study was to observe whether 1.8 GHz microwaves (MW) (SAR, 3 W/kg) exposure can influence human lymphocyte DNA damage induced by ultraviolet ray C (UVC). The lymphocytes, which were from three young healthy donors, were exposed to 254 nm UVC at the doses of 0.25, 0.5, 0.75, 1.0, 1.5 and 2.0 J m(-...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2007.01.019
更新日期:2007-04-11 00:00:00
abstract::The multiple cascades of signal transduction pathways that lead from receptors on the cell membrane to the nucleus, thus translating extracellular signals into changes in gene expression, may represent important targets for neurotoxic compounds. Among the biochemical steps and pathways that have been investigated are ...
journal_title:Toxicology
pub_type: 杂志文章,评审
doi:10.1016/s0300-483x(00)00435-2
更新日期:2001-03-07 00:00:00
abstract::Dimethyl sulfoxide (DMSO) has previously been shown to protect against acetaminophen (APAP)-induced hepatotoxicity, but the mechanism of this effect was not clear. Treatment of mice with 1 mg/kg DMSO 4 h before 250 mg/kg APAP resulted in significantly less hepatotoxicity than with APAP alone, as measured by serum glut...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(88)90202-8
更新日期:1988-11-14 00:00:00
abstract::This study aimed to prove that prenatal ethanol exposure (PEE) can induce nephrotic syndrome in male rat offspring and to explore the underlying intrauterine programming mechanisms. Pregnant Wistar rats were intragastrically administered ethanol (4 g/kg d) from gestational day (GD) 9 to GD 20, and the male fetuses wer...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2018.03.004
更新日期:2018-05-01 00:00:00
abstract::The teratogenicity of antiepilepsy drug valproic acid (VPA) mostly is found in genetic and somatic levels, causing teratogenesis involving neurotubular defects (NTDs), anencephaly, lumbosacral meningomyelocele, and leg dysfunction due to spina bifida aperta. A diversity of nutraceutics have been tried to alleviate the...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2011.10.015
更新日期:2012-01-27 00:00:00
abstract::Synthetic pyrethroids are one of the most frequently and widely used class of insecticides, primarily because they have a higher insect to mammalian toxicity ratio than organochlorines or organophosphates. The basic structure of pyrethroids can be characterized as an acid joined to an alcohol by an ester bond. Pyrethr...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2009.10.003
更新日期:2010-01-12 00:00:00
abstract::Unfortunately, the principal routine toxicology methods employed for the safety assessment of new products are over 40 years old and rely primarily on histopathological evaluation. It is difficult to introduce newer immunotoxicology or molecular toxicology methods into toxicity assessment without extensive and time co...
journal_title:Toxicology
pub_type: 杂志文章,评审
doi:10.1016/s0300-483x(96)03601-3
更新日期:1997-04-11 00:00:00
abstract::Effects of metallothionein (MT) synthesis inhibiting compounds (actinomycin D, cycloheximide), MT synthesis stimulating compounds (dexamethasone, dibu-cAMP) and interfering metals (Cd, Zn) on copper accumulation were investigated in rat hepatoma tissue culture cells. Copper-metallothionein (Cu-MT) and MT-associated co...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(94)90168-6
更新日期:1994-09-06 00:00:00
abstract::The guinea pig maximization test (GPMT) has been used as a method for the prediction of skin sensitizing potential for over 30 years. Besides hazard identification, risk assessment of sensitizing chemicals requires the assessment of potency. For the determination of potency based on lowest effective dose levels, dose-...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/s0300-483x(01)00425-5
更新日期:2001-10-30 00:00:00
abstract::The usefulness of measuring serum bile acid concentrations by RIA in a number of acute experimental liver injuries of rats was assessed by comparing the concentrations with the results of some of the routinely employed methods of examining hepatotoxic changes. Centrilobular liver cell injury produced by CCl4 revealed ...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(80)90005-0
更新日期:1980-01-01 00:00:00
abstract::Groundwater arsenic contamination has become a serious global concern due to its adverse effects on human health. Arsenic-induced reactive oxygen species trigger oxidative stress inside mitochondria, which initiate a cascade of events including altered mitochondrial (mt) membrane potential, uncoupling of electron tran...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2018.06.012
更新日期:2018-09-01 00:00:00
abstract::The potential of single, toxic doses of fenitrothion (O,O-dimethyl O-(4-nitro-m-tolyl)phosphorothioate) to elicit delayed neurotoxicity in the adult White Leghorn hen was compared to the effects produced following similar treatment with the known neurotoxin, tri-o-tolyl phosphate (TOTP). Hens (2.0-2.5 kg body wt) rece...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(86)90185-x
更新日期:1986-11-01 00:00:00
abstract::The early neonatal stage constitutes a sensitive period during which exposure to adverse events can increase the risk of neuropsychiatric disorders. Maternal deprivation (MD) is a model of early life stress that induces long-term behavioural and physiological alterations, including susceptibility to different drugs of...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2012.12.003
更新日期:2013-09-06 00:00:00
abstract::Bisphenol A (BPA) is a commonly used endocrine-disrupting chemical used as a component of polycarbonates plastics that has potential adverse effects on human health. Exposure to BPA during development has been implicated in memory deficits, but the mechanism of action underlying the effect is not fully understood. In ...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2016.01.010
更新日期:2016-02-03 00:00:00