Abstract:
:There is a subpopulation of the CF-1 mouse strain that is very sensitive to the neurotoxicity induced by the avermectins, a class of natural products widely used in veterinary and human medicine as anti-parasitic agents. This sensitivity results from a lack of P-glycoprotein in the intestine and brain of sensitive animals, allowing increased penetration of these compounds in the blood and brain, respectively. We describe a restriction fragment length polymorphism that is able to predict which animals will be deficient in this protein, confirming at the genetic level a heterogeneous population of this mouse strain. Breeding studies demonstrated that the inheritance of the markers follows a normal Mendelian autosomal pattern. Sensitive "-/-" animals are deficient in P-glycoprotein in those tissues known to express primarily mdr1a, but have normal P-glycoprotein levels in tissues known to express primarily mdr1b or mdr2, suggesting that the defect in the sensitive animals is limited to the mdr1a gene. The P-glycoprotein expression in the brain is dependent on the genotype, which also determines the susceptibility to the avermectin-induced neurotoxicity, with the "-/-" animals being most sensitive, and the "+/-" animals having less P-glycoprotein and therefore increased CNS sensitivity compared to the "+/+" animals. The ability to segregate this strain into -/- and +/+ animals may prove useful for examining the physiological role of P-glycoprotein in drug absorption and distribution and related toxicity. These data also provide a warning that experiments carried out with P-glycoprotein substrates in the heterogeneous population of the CF-1 mouse must be interpreted with caution.
journal_name
Toxicol Appl Pharmacoljournal_title
Toxicology and applied pharmacologyauthors
Umbenhauer DR,Lankas GR,Pippert TR,Wise LD,Cartwright ME,Hall SJ,Beare CMdoi
10.1006/taap.1997.8225subject
Has Abstractpub_date
1997-09-01 00:00:00pages
88-94issue
1eissn
0041-008Xissn
1096-0333pii
S0041-008X(97)98225-9journal_volume
146pub_type
杂志文章abstract::Rats were given an ip injection of T-2 mycotoxin (T-2), the T-2 metabolite, T-2 tetraol (tetraol), or cycloheximide. Serum, liver, heart, kidney, spleen, muscle, and intestine were collected at 3, 6, and 9 hr postinjection after a 2-hr pulse at each time with [14C]leucine and [3H]thymidine. Protein and DNA synthesis l...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(90)90151-j
更新日期:1990-09-15 00:00:00
abstract::The effect of mucosal metallothionein (MT) preinduced by zinc (Zn) on tissue distribution of cadmium (Cd) after administration of Cd with several chelating agents was studied in rats. After Cd-cysteine (Cd-Cys) was incubated with intestinal Zn-MT in vitro, all the Cd dissociated from Cys and exchanged the Zn bound to ...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(92)90129-g
更新日期:1992-04-01 00:00:00
abstract::Studies were conducted which examined urinary excretion and papillary production of cyclic-AMP in the rat following vasopressin (ADH) stimulation in the presence or absence of inorganic fluoride ion (F). In one set of experiments, six anesthetized Fischer 344 rats were administered 5 munits arginine vasopressin during...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(83)90129-1
更新日期:1983-06-15 00:00:00
abstract::Primary mixed cultures of Sertoli and germ cells were prepared from testes of immature rats and their response to the known testicular toxicants ethylene glycol monomethyl ether (EGM) and ethylene glycol monoethyl ether (EGE) was studied. Neither EGM nor EGE produced any morphological evidence of toxicity when added t...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(85)90146-2
更新日期:1985-07-01 00:00:00
abstract::Chlorinated dibenzo-p-dioxins (CDDs) are a series of mono- to octa-chlorinated homologous chemicals commonly referred to as polychlorinated dioxins. One of the most potent, well-known, and persistent member of this family is 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). As part of translational research to make computer...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2016.12.007
更新日期:2017-01-15 00:00:00
abstract::Recent advances have been made in our understanding of the roles played by cutaneous dendritic cells (DCs) in the induction of contact allergy. A number of associated changes in epidermal Langerhans cell phenotype and function required for effective skin sensitization are providing the foundations for the development ...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.taap.2007.03.006
更新日期:2007-06-15 00:00:00
abstract::The concept of toxicovigilance encompasses the active detection, validation and follow-up of clinical adverse events related to toxic exposures in human beings. Poison centers are key players in this function as poisoning statistics are essential to define the cause, incidence and severity of poisonings occurring in t...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.taap.2005.02.019
更新日期:2005-09-01 00:00:00
abstract::Valproic acid (VPA) undergoes cytochrome P450-mediated desaturation to form 4-ene-VPA, which subsequently yields (E)-2,4-diene-VPA by β-oxidation. Another biotransformation pathway involves β-oxidation of VPA to form (E)-2-ene-VPA, which also generates (E)-2,4-diene-VPA by cytochrome P450-mediated desaturation. Althou...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2012.08.018
更新日期:2012-11-01 00:00:00
abstract::Male, English smooth haired guinea pigs were exposed to thermal decomposition products, i.e., smoke, generated by heating Douglas fir in an open system. Various amounts of Douglas fir were placed in a furnace, at room temperature, and heated at a rate of 11 degrees C/min until completely decomposed. Major decompositio...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(84)90077-2
更新日期:1984-08-01 00:00:00
abstract::4-Aminobiphenyl (4-ABP), an aromatic amine present in tobacco smoke, is an animal and human carcinogen. 4-ABP can undergo several biotransformation reactions to yield DNA-binding species. The role of acetylation in the biotransformation of 4-ABP to reactive intermediates was investigated by determining mutagenicity in...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1999.8727
更新日期:1999-09-01 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 cumulative exposure to estrogens is an important determinant in the risk of breast cancer, yet the full range of mechanisms involving estrogens in the genesis and progression of breast cancer remains a subject of debate. Interactions of estrogens and environmental toxicants have received attention as putative fact...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2009.07.013
更新日期:2009-11-01 00:00:00
abstract::Male rats were injected SC with 0.6 mg Cd/kg/day for 5 days per week for 2, 4, 6, and 8 weeks. Liver and kidney were examined morphologically and analyzed for metallothionein, cadmium, zinc, and copper. Morphologic changes were found in kidney but not in liver. The earliest ultrastructural change consisted of myelin f...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(89)90272-x
更新日期:1989-11-01 00:00:00
abstract::3-Methylindole (3-MI) is a pneumotoxic metabolite of L-tryptophan that can form in the digestive tracts of humans and ruminants as a result of microbial protein metabolism. Alternatively, human lungs can be directly exposed to 3-MI formed during protein pyrolysis and inhalation of tobacco smoke. 3-MI has been shown to...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(91)90001-u
更新日期:1991-07-01 00:00:00
abstract::The effect of butylated hydroxytoluene (BHT), which is used widely as an antioxidant, on IgE-dependent allergic responses in vivo and in vitro was investigated. For in vivo study, passive cutaneous anaphylaxis (PCA) was elicited in rats by i.d. injection of anti-DNP IgE and 48 h later by i.v. injection of DNP-HSA. BHT...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2007.05.007
更新日期:2007-09-01 00:00:00
abstract::The putative neurotoxicity of the organophosphorus compound triphenyl phosphite (TPP) was examined in Long Evans, adult male rats. Animals were exposed to two 1.0 ml/kg (1184 mg/kg) injections (sc) of TPP spaced 1 week apart and sampled for biochemical and neuropathological examination. At the time of sampling, rats d...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(86)90297-8
更新日期:1986-04-01 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::Numbers of engineered nanomaterials (ENMs) are steadily increasing. Therefore, alternative testing approaches with reduced costs and high predictivity suitable for high throughput screening and prioritization are urgently needed to ensure a fast and effective development of safe products. In parallel, extensive resear...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2016.01.019
更新日期:2016-05-15 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::The dermal sensitizing potencies of four diisocyanates were investigated using the mouse ear-swelling test (MEST) with BALB/cBy mice. Mice were administered topical doses of diisocyanates to the abdomen and were challenged on the ear 4 days later with a nonirritating dose of chemical. The increase in ear thickness at ...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(87)90093-7
更新日期:1987-01-01 00:00:00
abstract::Ochratoxin A (OTA) is a mycotoxin that is found in various food and feed products. The molecular mechanisms that are associated with OTA hepatotoxicity and teratogenicity have not been extensively elucidated in a developing organism. In this study, the transcriptomic profile of zebrafish embryos indicates that hemosta...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2017.12.012
更新日期:2018-02-01 00:00:00
abstract::St. John's wort (SJW, Hypericum perforatum) is one of the popular nutraceuticals for treating depression. Methotrexate (MTX) is an immunosuppressant with narrow therapeutic window. This study investigated the effect of SJW on MTX pharmacokinetics in rats. Rats were orally given MTX alone and coadministered with 300 an...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2012.05.020
更新日期:2012-08-15 00:00:00
abstract::The effects of oral exposure to 0, 5, and 25 mg/kg body wt vomitoxin (VT) on cytokine mRNA levels in spleen, Peyer's patches (PP), liver, kidney, and small intestine were evaluated in B6C3F1 mice at 2 and 4 hr postexposure using RT-PCR in conjunction with Southern hybridization analysis. The abundance of mRNAs for sev...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1995.1132
更新日期:1995-07-01 00:00:00
abstract::Recent data suggest that vanadium (V5+) compounds exert protective effects against chemical-induced carcinogenesis, mainly through modifying various xenobiotic metabolizing enzymes. In fact, we have shown that V5+ down-regulates the expression of Cyp1a1 at the transcriptional level through an ATP-dependent mechanism. ...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2009.02.002
更新日期:2009-05-01 00:00:00
abstract::Dantrolene is an effective antagonist of anesthesia-induced malignant hyperthermia due to a poorly understood action on skeletal muscle. The present study examines whether the red blood cell can be used as a model to investigate the mechanism of dantrolene action. Halothane (4.7 mM) caused 9% hemolysis of red blood ce...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(87)90133-5
更新日期:1987-09-30 00:00:00
abstract::Arsenic ingestion has been linked to increasing global prevalence of and mortality from cardiovascular disease (CVD); arsenic can be removed from drinking water to reduce related health effects. Lactate dehydrogenase (LDH) is used for the evaluation of acute arsenic toxicity in vivo and in vitro, but it is not validat...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2012.04.028
更新日期:2012-08-01 00:00:00
abstract::A great number of people are suffering from allergic inflammatory disease such as asthma, atopic dermatitis, and sinusitis. Therefore discovery of drugs for the treatment of these diseases is an important subject in human health. Putranjivain A (PJA), member of ellagitannin, is known to possess beneficial effects incl...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2013.12.006
更新日期:2014-02-01 00:00:00
abstract::Antineoplastic drugs cause severe cytotoxicity for normal cells, especially hematopoietic stem cells (HSCs). However, bleomycin (BLM) is glycopeptide antibiotic that is effective on various cancers and has either low or no myelosuppression effects. The aim of the present study was to investigate the effect of BLM on 5...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2020.114996
更新日期:2020-06-01 00:00:00
abstract::Nonylphenol (NP), a by-product of alkylphenol ethoxylates, is a pervasive surfactant that activates the xenosensing nuclear receptor, the pregnane X-receptor (PXR) in transactivation assays in vitro. We are interested in determining if NP activates PXR in vivo, determining if hPXR and mPXR act similarly, and investiga...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2011.02.017
更新日期:2011-05-01 00:00:00
abstract::Calcium uptake in cells occurs through specific membrane channels. Since cadmium and mercury inhibit calcium uptake, this study examined whether the calcium channels may also be involved in the uptake of these metals. Primary cultures of rat hepatocytes were incubated with 3 microM CdCl2 or HgCl2 in the absence or pre...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/s0041-008x(05)80018-3
更新日期:1991-09-01 00:00:00