Abstract：
:Endosulfan is an organochlorine pesticide commonly used in agriculture. Endosulfan has affects on vertebrate xenobiotic metabolism pathways that may be mediated, in part, by its ability to activate the pregnane X receptor (PXR) and/or the constitutive androstane receptor (CAR) which can elevate expression of cytochrome P450 (CYP) enzymes. This study examined the dose-dependency and receptor specificity of CYP induction in vitro and in vivo. The HepG2 cell line was transiently transfected with CYP2B6- and CYP3A4-luciferase promoter reporter plasmids along with human PXR (hPXR) or hCAR expression vectors. In the presence of hPXR, endosulfan-alpha exposure caused significant induction of CYP2B6 (16-fold) and CYP3A4 (11-fold) promoter activities over control at 10 microM. The metabolite endosulfan sulfate also induced CYP2B6 (12-fold) and CYP3A4 (6-fold) promoter activities over control at 10 microM. In the presence of hCAR-3, endosulfan-alpha induced CYP2B6 (2-fold) promoter activity at 10 microM, but not at lower concentrations. These data indicate that endosulfan-alpha significantly activates hPXR strongly and hCAR weakly. Using western blot analysis of human hepatocytes, the lowest concentrations at which CYP2B6 and CYP3A4 protein levels were found to be significantly elevated by endosulfan-alpha were 1.0 microM and 10 microM, respectively. In mPXR-null/hPXR-transgenic mice, endosulfan-alpha exposure (2.5mg/kg/day) caused a significant reduction of tribromoethanol-induced sleep times by approximately 50%, whereas no significant change in sleep times was observed in PXR-null mice. These data support the role of endosulfan-alpha as a strong activator of PXR and inducer of CYP2B6 and CYP3A4, which may impact metabolism of CYP2B6 or CYP3A4 substrates.
journal_name
Toxicol Appl Pharmacoljournal_title
Toxicology and applied pharmacologyauthors
Casabar RC,Das PC,Dekrey GK,Gardiner CS,Cao Y,Rose RL,Wallace ADdoi
10.1016/j.taap.2010.03.017subject
Has Abstractpub_date
2010-06-15 00:00:00pages
335-43issue
3eissn
0041-008Xissn
1096-0333pii
S0041-008X(10)00114-6journal_volume
245pub_type
杂志文章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：:To investigate the mechanisms of erythromycin cholestasis, the effects of erythromycin estolate (EE) on the excretory function of the isolated perfused rat liver and on liver plasma membrane (LM) preparations were studied and compared to those of erythromycin base (EB) and lauryl sulfate (LS), added alone or in combin...
journal_title：Toxicology and applied pharmacology
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doi：10.1016/0041-008x(85)90074-2
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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
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(89)90132-4
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abstract：:Diesel exhaust particles (DEPs) cause many adverse health problems, and reports indicate increased risk of breast cancer in men and women through exposure to gasoline and vehicle exhaust. However, DEPs include vast numbers of compounds, and the specific compound(s) responsible for these actions are not clear. We recen...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2008.02.027
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(83)90191-6
更新日期：1983-08-01 00:00:00
abstract：:Radiolabeled 1-naphthyl-beta-D-glucuronide and 1-naphthyl-beta-D-glucoside were synthesized from 1-[14C]naphthol. The fate of the three compounds in male mice was studied. After a po dose of 45 mg/kg of 1-naphthol, 100 mg/kg of 1-naphthyl glucuronide, and 100 mg/kg of 1-naphthyl glucoside, 95, 93, and 81%, respectivel...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(83)90313-7
更新日期：1983-03-15 00:00:00
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(90)90050-5
更新日期：1990-03-01 00:00:00
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2008.09.025
更新日期：2009-01-01 00:00:00
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2012.10.008
更新日期：2012-12-01 00:00:00
abstract：:Isoflurane is known to increase β-amyloid aggregation and neuronal damage. We hypothesized that isoflurane will have similar effects on the polyglutamine huntingtin protein and will cause alterations in intracellular calcium homeostasis. We tested this hypothesis in striatal cells from the expanded glutamine huntingti...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2010.10.032
更新日期：2011-02-01 00:00:00
abstract：:Low dietary concentrations of methionine and cysteine are known to decrease hepatic glutathione content. However, it is not known if restricting the dietary content of these sulfur containing amino acids also affects hepatic levels of adenosine 3'-phosphate 5'-phosphosulfate (PAPS), the cofactor for sulfation, or meta...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(90)90025-p
更新日期：1990-02-01 00:00:00
abstract：:Health agencies are often required to predict the effects of long term low level exposure in humans based on annual data involving short-term high-level exposures. Uncertainties in extrapolation can be, in part, based on potentially different mechanism associated with different exposure scenarios. This study evaluated...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1006/taap.1996.0155
更新日期：1996-07-01 00:00:00
abstract：:Polychlorinatedbiphenyls (PCBs) are a group of persistent and widely dispersed environmental pollutants, some of which may be immunotoxic. In the present study, we investigated the effect of PCBs on immune system by assessing apoptotic cell death in human monocytic U937 cells. Among the various congeners tested, 2,2',...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1006/taap.2000.9034
更新日期：2000-11-15 00:00:00
abstract：:Benzene is a potent bone marrow toxicant. While all blood cell types are targets for benzene poisoning, lymphocytes are particularly sensitive. The immunotoxic consequences of benzene or its metabolites have been demonstrated in a number of in vitro studies; however, little data exist regarding the effects of benzene ...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(85)90395-3
更新日期：1985-09-30 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
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2012.07.029
更新日期：2012-10-15 00:00:00
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/s0041-008x(03)00234-5
更新日期：2003-08-01 00:00:00
abstract：:Following exposure to 2 ppm ozone for 4 hr, two distinct effects on rat lung inflammatory cell oxidant generation were observed. TPA- and opsonized zymosan-stimulated superoxide production by the inflammatory cell population was found to be maximally inhibited 24 hr following ozone exposure. In contrast, luminol-ampli...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(89)90005-7
更新日期：1989-06-15 00:00:00
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journal_title：Toxicology and applied pharmacology
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doi：10.1016/0041-008x(90)90364-z
更新日期：1990-08-01 00:00:00
abstract：:Herb-drug interaction strongly limits the clinical application of herbs and drugs, and the inhibition of herbal components towards important drug-metabolizing enzymes (DMEs) has been regarded as one of the most important reasons. The present study aims to investigate the inhibition potential of andrographolide derivat...
journal_title：Toxicology and applied pharmacology
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更新日期：2014-05-15 00:00:00
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journal_title：Toxicology and applied pharmacology
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doi：10.1016/j.taap.2020.115245
更新日期：2020-11-15 00:00:00
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journal_title：Toxicology and applied pharmacology
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doi：10.1016/j.taap.2014.07.019
更新日期：2014-10-01 00:00:00
abstract：:Disintegrins and disintegrin-like proteins are molecules found in the venom of four snake families (Atractaspididae, Elapidae, Viperidae, and Colubridae). The disintegrins are nonenzymatic proteins that inhibit cell-cell interactions, cell-matrix interactions, and signal transduction, and may have potential in the tre...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2005.07.004
更新日期：2006-04-01 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：:Non-small cell lung cancer (NSCLC) patients harboring EGFR mutation who initially respond to EGFR-TKI will gradually develop acquired resistance. There is still a challenge to treat EGFR-TKI resistant NSCLC patients. Polyphyllin I (PP I), a steroidal saponin isolated from Paris polyphylla., has been exhibited antitumo...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2018.07.031
更新日期：2018-10-01 00:00:00
abstract：:Depression is one of the most common psychiatric disorders in the world. Andrographolide is a natural product that displays evident anti-inflammatory activities. The purpose of the present study was to explore the antidepressant potential of andrographolide in chronic unpredictable mild stress (CUMS)-induced depressiv...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2019.114688
更新日期：2019-09-15 00:00:00
abstract：:Homocysteine is increased during pathological conditions, endangering vascular and cognitive functions, and elevated homocysteine during pregnancy may be correlated with an increased incidence of schizophrenia in the offspring. This study showed that millimolar homocysteine concentrations in saline medium cause phosph...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2009.10.010
更新日期：2010-01-15 00:00:00
abstract：:This pilot study was designed to assess whether a synthetic matrix metalloproteinase (MMP) inhibitor has anti-inflammatory properties in mild asthma. Tumor necrosis factor alpha (TNFalpha) has been shown to be an important cytokine in the pathogenesis of allergic airway inflammatory responses, and its release can be i...
journal_title：Toxicology and applied pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1016/j.taap.2004.10.005
更新日期：2005-06-01 00:00:00
abstract：:MCC-555 is a novel PPARα/γ dual ligand of the thiazolidinedione class and was recently developed as an anti-diabetic drug with unique properties. MCC-555 also has anti-proliferative activity through growth inhibition and apoptosis induction in several cancer cell types. Our group has shown that MCC-555 targets several...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2012.06.014
更新日期：2012-09-01 00:00:00
