Abstract:
:Benzodiazepines have wide-spread used in pharmacotherapy for their anxiolytic, myorelaxant, hypnotic, amnesic and anticonvulsive properties. Despite benzodiazepines are used in clinics over 50 years, they have not been surprisingly tested for capability to induce major drug-metabolizing cytochromes P450. In the current study, we have examined the potency of Alprazolam, Bromazepam, Chlordiazepoxide, Clonazepam, Diazepam, Lorazepam, Medazepam, Midazolam, Nitrazepam, Oxazepam, Tetrazepam and Triazolam to induce CYP1A2 and CYP3A4 in primary cultures of human hepatocytes. Benzodiazepines were tested in therapeutic concentrations and in concentrations corresponding to their plasma levels in intoxicated patients. We found weak but significant induction of CYP3A4 mRNA by Midazolam and Medazepam, while other benzodiazepines did not induce CYP3A4 expression. None of the tested compounds induced CYP1A2 mRNA in three independent human hepatocytes cultures. In addition, employing gene reporter assays with transiently transfected hepatocarcinoma cells, we found that tested benzodiazepines did not activate aryl hydrocarbon receptor (AhR), whereas Midazolam and Medazepam slightly activated pregnane X receptor (PXR). Consistently, two-hybrid mammalian assay using hybrid fusion plasmids GAL4-PXR ligand-binding domain (LBD) and VP16-SRC-1-receptor-interacting domain (RID) confirmed PXR activation by Midazolam and Medazepam. In conclusion, Alprazolam, Bromazepam, Chlordiazepoxide, Clonazepam, Diazepam, Lorazepam, Nitrazepam, Oxazepam, Tetrazepam and Triazolam can be considered as safe drugs in term of their inability to induce PXR- and AhR-dependent cytochrome P450 enzymes CYP1A2 and CYP3A4. Medazepam and Midazolam slightly activated pregnane X receptor and displayed weak potency to induce CYP3A4 mRNA in human hepatocytes.
journal_name
Toxicol Lettjournal_title
Toxicology lettersauthors
Vrzal R,Kubesova K,Pavek P,Dvorak Zdoi
10.1016/j.toxlet.2010.01.004subject
Has Abstractpub_date
2010-03-15 00:00:00pages
183-8issue
2eissn
0378-4274issn
1879-3169pii
S0378-4274(10)00018-4journal_volume
193pub_type
杂志文章abstract::Hypoallergenic infant formulas are widely used for infants with cow's milk allergy. The aim of this study was to assess the utility of the mouse basophil activation test (BAT) in the evaluation of residual antigenicity in these formulas. Whole blood samples derived from β-lactoglobulin- or casein-immunized mice were i...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2015.11.024
更新日期:2016-02-03 00:00:00
abstract::A number of retrospective studies have suggested that choice of anesthetic drugs during surgical tumor resection might affect tumor recurrence/metastasis, or outcome of patients. The recent study showed that volatile anesthetics-based general anesthesia was associated with the worse outcomes than intravenous anestheti...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2016.12.007
更新日期:2017-01-15 00:00:00
abstract::The in vitro interactions of carbaryl and carcinogenic N-nitrosocarbaryl with rat liver microsomal monooxygenase activities are compared. The inhibitory effect of the nitroso-compound is demonstrated to be non-competitive on aminopyrine N-demethylase, p-nitroanisole O-demethylase and aniline hydroxylase. The nature of...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(89)90016-7
更新日期:1989-02-01 00:00:00
abstract::Hsp90, p23 and other chaperosome proteins are critical for the function of several enzymes and steroid hormone receptors. The dioxin receptor (DR) is an Hsp90-regulated transcription factor that binds numerous toxic ligands, including the environmental contaminant 2,3,7,8-tetrachlorodibenzo(p)dioxin. We used a yeast m...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/s0378-4274(01)00465-9
更新日期:2002-03-24 00:00:00
abstract::Nonylphenol (NP) is a representative endocrine disruptor that has an adverse effect on male reproduction and posses direct hazard to Sertoli cells, but the mechanism remains incompletely elucidated. In the present study, based on the structural comparability and high affinity between NP and membrane phospholipid molec...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2008.08.011
更新日期:2008-12-15 00:00:00
abstract::With the multitude of new chemicals being synthesized and the paucity of long-term test data on chemicals that could be introduced into the environment, innovative approaches must be developed to determine the health and environmental effects of chemicals. Research was conducted to employ quantitative structure-activi...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(95)03365-r
更新日期:1995-09-01 00:00:00
abstract::Most studies on the adverse effects of air pollution have focused on respiratory and cardiovascular diseases, and there are relatively few studies on eye diseases following exposure of ambient particulate matter (PM). Epidemiological and clinical researches correlating the eye and PMs have recently received attention....
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2017.12.012
更新日期:2018-03-01 00:00:00
abstract::Hepatic and renal microsomal electron transport components and erythrocyte delta-aminolevulinate dehydratase were investigated in adult male rats exposed to 0, 50, 200 and 600 ppm tetrachloroethylene for 4 weeks. Body weight and liver weight showed a significant decrease only in the 600 ppm group. A dose-dependent dec...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(90)90185-o
更新日期:1990-12-01 00:00:00
abstract::Heptachlor is a major component of the insecticide, chlordane. It is a health hazard but is still in use in some countries of Southeast Asia. To elucidate the toxicity of heptachlor its effects on mice after oral and intraperitoneal administration were studied. A 3-day group, 92-day group and 180-day group were given ...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(90)90054-p
更新日期:1990-11-01 00:00:00
abstract::Sulfur mustard (SM) is a highly toxic chemical warfare agent, which produces blisters after skin contact. Treatment of SM-induced adverse health effects, such as cutaneous blistering, ulceration, and inflammation remains a challenging task. Antidotes or specific therapeutic measures are lacking. Some drugs (e.g. cyclo...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2019.03.012
更新日期:2019-09-15 00:00:00
abstract::The industrial solvent dioxane (1,4-diethylene dioxide) was evaluated for teratogenic potential in Sprague-Dawley rats. The compound was administered on days 6-15 of gestation by gavage (0, 0.25, 0.5 and 1.0 ml/kg/day). A slight maternal toxicity, as evidenced by reduced weight gain, was observed with 1.0 ml/kg. Anima...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(85)90189-4
更新日期:1985-07-01 00:00:00
abstract::Benzo(a)pyrene (BP) is the best studied polycyclic aromatic hydrocarbon, classified as carcinogenic to humans. The carcinogenic metabolite, benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE), binds covalently to DNA. The key enzyme in this metabolic reaction is CYP1A1, which has also been found in placenta and human t...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2010.04.028
更新日期:2010-08-16 00:00:00
abstract::Because coarse mode particles are rarely studied in their existing size ranges (greatest mass about 5-7 microns, aerodynamic diameter), we investigated the effects of four such particles, quartz, ferric oxide, calcium carbonate, and sodium feldspar, on host defenses against bacterial pulmonary infection. Mice which re...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(83)90263-1
更新日期:1983-10-01 00:00:00
abstract::Modulation of the cytochrome P450 (CYP) monooxygenase system by cadmium was investigated in male, adult DBA/2J mice treated with a single dose (16 micromol/kg body weight, i.p.) of cadmium chloride (CdCl2). Total CYP content of liver and kidney microsomes decreased maximally (56% and 85%, respectively) 24 and 18 h, re...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2003.10.029
更新日期:2004-03-21 00:00:00
abstract::In this paper, the difficulties of genetic screening of occupationally exposed subjects for the evaluation of retrospective, and prospective, health risk assessments is illustrated with reference to glutathione S-transferase (GST) function. Individual differences in the magnitude and half-life of adduct levels, derive...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/s0378-4274(02)00191-1
更新日期:2002-08-05 00:00:00
abstract::Accumulation of macrophages and neutrophil granulocytes in the lung are key events in the inflammatory response to inhaled particles. The present study aims at the time course of chemotaxis in vitro in response to the challenge of various biopersistent particles and its functional relation to the transcription of infl...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2016.08.014
更新日期:2016-11-30 00:00:00
abstract::A short-term initiation/promotion bioassay has been developed in rat liver using putative preneoplastic foci as the endpoint for the detection of chemical carcinogens. The two protocols of the bioassay used in this study were varied according to the time 2/3 partial hepatectomy was performed in relation to when the in...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(82)90177-1
更新日期:1982-07-01 00:00:00
abstract::In this study, we aimed to evaluate the genotoxic effects of fungicides fenarimol and propamocarb which are used to protect crops from fungi. For this reason, bone-marrow micronucleus and chromosome aberration tests were carried out in Swiss albino mice. Mice were injected with four different doses of fenarimol and pr...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2003.10.015
更新日期:2004-02-28 00:00:00
abstract::Troglitazone (Tro) is a thiazolidinedione antidiabetic drug that was withdrawn from the market due to its association with idiosyncratic severe liver injury. Tro has never induced liver injury in experimental animals in vivo. It was assumed that the species differences between human and experimental animals in the pha...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2012.08.001
更新日期:2012-10-02 00:00:00
abstract::Metal oxide NPs are abundantly produced in nanotech industries and are emitted in several combustion processes, suggesting the need to characterize their toxic impact on the human respiratory system. The acute toxicity and the morphological changes induced by copper oxide and titanium dioxide NPs (nCuO and nTiO₂) on t...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2013.07.019
更新日期:2013-10-24 00:00:00
abstract::Exposure of C57Bl mice to 10 ppm benzene (the current occupational exposure limit) for 6 h/day, 5 days/week causes a progressive depression in the in vitro colony forming ability of one of the erythroid progenitor cells, the colony-forming unit-erythroid (CFU-E). Colony growth of cells from exposed mice was only 5% of...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(84)90169-3
更新日期:1984-03-01 00:00:00
abstract::Nuclear accumulation of the tumorsuppressor protein p53 indicates the occurrence of chromatin injury (J. Cancer Res. Clin. Oncol. 1991, 117, 30; Oncogene 1993, 8, 307) and may be used as an analytical tool to detect genotoxic agents. This mechanism was used to evaluate the DNA-damaging potency (clastogenicity) of the ...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(96)03711-3
更新日期:1996-11-01 00:00:00
abstract::As information regarding microarray data sets and toxicogenomic biomarkers grows rapidly, the process of analyzing data and interpreting the results is increasingly complicated. To facilitate data analysis, a simple expression ratio-based scoring method called the TGP1 score was previously proposed [Kiyosawa, N., Shiw...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2009.03.011
更新日期:2009-07-24 00:00:00
abstract::The effects of lead exposure have been studied upon the behavioural and diuretic responses to the kappa-opioid receptor agonist U-50488H in neonatal rats. Lead was administered in the maternal drinking water (100, 300 and 1000 ppm) from conception to postnatal day 14. The hyperactivity, wall climbing behaviours and di...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(90)90248-k
更新日期:1990-01-01 00:00:00
abstract::Hexachlorobenzene (HCB) and p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) kinetics were compared in rats before, during and after partial starvation. Food restriction produced a drastic mobilization of the residues stored in the adipose tissue resulting in symptoms of neurotoxicity. The redistribution was reversibl...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(88)90105-1
更新日期:1988-07-01 00:00:00
abstract::Due to advances in nanotechnology, exposure to particle compounds in the workplace has become unavoidable. Assessment of their toxicity on health is an important occupational safety issue. This study was conducted in mice to investigate the toxicological effects of submicron and nano-iron oxide particles on pulmonary ...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2012.02.004
更新日期:2012-05-05 00:00:00
abstract::The effect of zinc (Zn) administration on the uptake and retention of cadmium (Cd), copper (Cu) and Zn in liver, kidneys and testes of cadmium exposed rats was investigated. Exposure to Cd caused a significant increase in the uptake of these metals in the 3 organs. The administration of Zn after the Cd exposure had li...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(80)90165-4
更新日期:1980-02-01 00:00:00
abstract::N-(3,5-Dichlorophenyl)succinimide (NDPS) induces nephrotoxicity via one or more metabolites which arise from oxidation of the succinimide ring. The purpose of this study was to examine the nephrotoxic potential of N-(3,5-dichlorophenyl)-3-hydroxysuccinamic acid (3-NDHSA), a potential metabolite of NDPS and a positiona...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(89)90047-7
更新日期:1989-09-01 00:00:00
abstract::To help minimize errors and confusion in the scientific literature, a few principles can be followed. The original intent and hypothesis of each study should be made clear, and deviations from the initial purpose should be stated. The hypothesis-testing portions of the research need to be clearly differentiated from t...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(95)03554-0
更新日期:1995-12-01 00:00:00
abstract:UNLABELLED:The Mre11, Rad50, and Nbs1 (MRN) complex is a DNA double-strand break sensor involved in DNA damage repair. Herein, we explored whether deletion of NAD(P)H:quinone oxidoreductase 1 (NQO1), a cytoprotective gene, affected MRN complex expression in the kidney after cisplatin-induced acute kidney injury (AKI)....
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2015.12.004
更新日期:2016-01-22 00:00:00