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Toxicology Letters

 
Articles from the last few issues of Toxicology Letters © Elsevier
 

A comparative study of the anticlastogenic effects of chlorophyllin on N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) or 7,12-dimethylbenz (α) anthracene (DMBA) induced micronuclei in mammalian cells in vitro and in vivo

  [CiTO]
Toxicology Letters, Vol. 214, No. 3. (November 2012), pp. 235-242, doi:10.1016/j.toxlet.2012.08.023

Abstract

Chlorophyllin (CHL), a water soluble derivative of chlorophyll has been shown to have both anticarcinogenic and antigenotoxic properties. We evaluated the protective effects of CHL (25 Î¼M in vitro, 4 and 100 mg/kg. b.w.) on the clastogenic action of two model carcinogens, MNNG and DMBA (25 Î¼M and 2 Î¼M respectively) in vitro on human hepatoma cells (HepG2) and (40 mg and 25 mg/Kg/b.w. respectively) in vivo on bone marrow of mice, using the frequencies of induced micronuclei as the end point. Pre-, post- and simultaneous treatments ...

 

Accumulation capacity of primary cultures of adipocytes for PCB-126: Influence of cell differentiation stage and triglyceride levels

  [CiTO]
Toxicology Letters, Vol. 214, No. 3. (November 2012), pp. 243-250, doi:10.1016/j.toxlet.2012.08.018

Abstract

Polychlorinated biphenyls (PCBs) are lipophilic persistent organic chemicals that accumulate at high concentrations in the adipose tissue. Recent studies correlate the presence of such contaminants in fat cells to possible alterations in the regulation of energy homeostasis in adipocytes. As the adipose tissue is composed of adipocytes at several stages of differentiation, it is possible that PCBs already accumulate in cells at an early stage, and thereby impair their development. The exact driving force enabling the massive accumulation of PCBs in ...

 

Silver nanoparticles effects on epididymal sperm in rats

  [CiTO]
Toxicology Letters, Vol. 214, No. 3. (November 2012), pp. 251-258, doi:10.1016/j.toxlet.2012.08.028

Abstract

The motivation of our study was to examine the acute effects of intravenously administered a single bolus dose of silver nanoparticles (AgNPs) on rat spermatogenesis and seminiferous tubules morphology. In the treated rats compared to the vehicle treated control animals, the experiments revealed a size-dependent (20 nm and 200 nm), dose-dependent (5 and 10 mg/kg body mass) and time-dependent (24 h, 7 and 28 days) decrease the epididymal sperm count measured by histological methods. In parallel AgNPs injection increased the level of DNA damage in germ ...

 

Estrogenic effects of fusarielins in human breast cancer cell lines

  [CiTO]
Toxicology Letters, Vol. 214, No. 3. (November 2012), pp. 259-262, doi:10.1016/j.toxlet.2012.09.004

Abstract

The fusarielins are a group of metabolites found in several Aspergillus and Fusarium species that have been reported to have with weak antifungal, antibiotic and cytotoxic effects. This study identifies fusarielin A, F, G and H isolated from Fusarium as mycoestrogens. Mycoestrogens are compounds from fungi that bind to the estrogen receptors and induce an estrogenic response in targeted cells. All four tested fusarielins stimulate MCF-7 cell proliferation with fusarielin H as the most potent, able to stimulate cell proliferation 4-fold ...

 

eNOS gene polymorphisms modify the association of PM10 with oxidative stress

  [CiTO]
Toxicology Letters, Vol. 214, No. 3. (November 2012), pp. 263-267, doi:10.1016/j.toxlet.2012.09.006

Abstract

Previous studies have suggested that air pollution increases various health outcomes through oxidative stress and oxidative stress-related genes modify the relationship between air pollution and health outcomes. Therefore, we evaluated the effect of PM10 on the levels of malondialdehyde (MDA), oxidative stress biomarker, and the effect modification by genetic polymorphisms of eNOS, oxidative stress-related gene, in the 560 Korean elderly. We obtained urine samples repeatedly from participants during five medical examinations between 2008 and 2010 and all ambient air pollutant concentration ...

 

An in vitro investigation of endocrine disrupting effects of trichothecenes deoxynivalenol (DON), T-2 and HT-2 toxins

  [CiTO]
Toxicology Letters, Vol. 214, No. 3. (November 2012), pp. 268-278, doi:10.1016/j.toxlet.2012.09.005

Abstract

Trichothecenes are a large family of chemically related mycotoxins. Deoxynivalenol (DON), T-2 and HT-2 toxins belong to this family and are produced by various species of Fusarium. The H295R steroidogenesis assay, regulation of steroidogenic gene expression and reporter gene assays (RGAs) for the detection of androgen, estrogen, progestagen and glucocorticoid (ant)agonist responses, have been used to assess the endocrine disrupting activity of DON, T-2 and HT-2 toxins. H295R cells were used as a model for steroidogenesis and gene expression studies and ...

 

Caffeine-induced fetal rat over-exposure to maternal glucocorticoid and histone methylation of liver IGF-1 might cause skeletal growth retardation

  [CiTO]
Toxicology Letters, Vol. 214, No. 3. (November 2012), pp. 279-287, doi:10.1016/j.toxlet.2012.09.007

Abstract

Several epidemiological investigations, including previous work by our laboratory, indicate that maternal caffeine consumption is associated with intrauterine growth retardation and impaired fetal length growth. Skeletal development is critical for length growth. In the present study, our goals were to determine the effects of prenatal caffeine exposures on fetal skeletal growth and to investigate the mechanisms associated with such effects. Pregnant Wistar rats were injected intragastrically with 120 mg/kg of caffeine intragastrically each day from gestational days 11–20. Maternal prenatal caffeine exposure ...

 

Effect of divalent metals on the neuronal proteasomal system, prion protein ubiquitination and aggregation

  [CiTO]
Toxicology Letters, Vol. 214, No. 3. (November 2012), pp. 288-295, doi:10.1016/j.toxlet.2012.09.008

Abstract

The role of normal cellular prion protein (PrP) remains to be fully elucidated; however, the protein is crucial for the infection and progression of prion diseases. Recent evidence indicates that PrP is a metalloprotein since the octapeptide repeat sequences in the protein have high affinity for various divalent cations and the binding sites appear to play a role in the pathogenesis of prion diseases. In our present study, we tested several divalent metals including manganese and cadmium and determined their effects ...

 

Gender differences in the liver micronucleus test in rats with partial hepatectomy

  [CiTO]
Toxicology Letters, Vol. 214, No. 3. (November 2012), pp. 296-300, doi:10.1016/j.toxlet.2012.09.003

Abstract

The liver micronucleus test in rats with partial hepatectomy is a useful method to detect pro-clastogens such as diethylnitrosamine, the active metabolites of which do not reach the bone marrow due to their short lifespan. We have already reported that structural or numerical chromosome aberration inducers should be given before or after partial hepatectomy, respectively, to detect genotoxicity in the liver of rats. In the present study, we found that the percentage of binucleated cells in the liver from naive male ...

 

TLR4 is a target of environmentally relevant concentration of lead

  [CiTO]
Toxicology Letters, Vol. 214, No. 3. (November 2012), pp. 301-306, doi:10.1016/j.toxlet.2012.09.009

Abstract

Lead (Pb) alters the susceptibility to different pathogens suggesting that macrophage-mediated defense mechanisms, through activation of toll-like receptors (TLRs), may be affected by Pb. The aim of this study was to test whether activation of TLR4 is a targeted molecule to the effect of environmentally relevant Pb concentrations (0.05, 0.5 and 5 Î¼g/dL). The function of macrophages activated through TLR4 was evaluated using as TLR4 ligand lipopolysaccharides (LPSs) from two different pathogens: Escherichia coli and Salmonella typhimurium. Pb induced proliferation, increased the ...

 

Prenatal nicotine exposure induced a hypothalamic–pituitary–adrenal axis-associated neuroendocrine metabolic programmed alteration in intrauterine growth retardation offspring rats

  [CiTO]
Toxicology Letters, Vol. 214, No. 3. (November 2012), pp. 307-313, doi:10.1016/j.toxlet.2012.09.001

Abstract

Prenatal nicotine exposure inhibits the functional development of the hypothalamic–pituitary–adrenal (HPA) axis and alters glucose and lipid metabolism in intrauterine growth retardation (IUGR) fetal rats, but the postnatal consequence is unknown. We aimed to verify a neuroendocrine metabolic programmed alteration in IUGR offspring whose mothers were subcutaneously treated with 2 mg/kg d of nicotine from gestational day 11 to 20. In the nicotine group, blood adrenocorticotropic hormone (ACTH) and corticosterone (CORT) levels were higher before postnatal day 35 and then returned to lower ...

 

Cannabidiolic acid, a major cannabinoid in fiber-type cannabis, is an inhibitor of MDA-MB-231 breast cancer cell migration

  [CiTO]
Toxicology Letters, Vol. 214, No. 3. (November 2012), pp. 314-319, doi:10.1016/j.toxlet.2012.08.029

Abstract

Cannabidiol (CBD), a major non-psychotropic constituent of fiber-type cannabis plant, has been reported to possess diverse biological activities, including anti-proliferative effect on cancer cells. Although CBD is obtained from non-enzymatic decarboxylation of its parent molecule, cannabidiolic acid (CBDA), few studies have investigated whether CBDA itself is biologically active. Results of the current investigation revealed that CBDA inhibits migration of the highly invasive MDA-MB-231 human breast cancer cells, apparently through a mechanism involving inhibition of cAMP-dependent protein kinase A, coupled with an ...

 

Chronic exposure to sulfur dioxide enhances airway hyperresponsiveness only in ovalbumin-sensitized rats

  [CiTO]
Toxicology Letters, Vol. 214, No. 3. (November 2012), pp. 320-327, doi:10.1016/j.toxlet.2012.09.010

Abstract

Sulfur dioxide (SO2) is a common air pollutant that triggers asthmatic symptoms, but its toxicological mechanisms are not fully understood. Specifically, it is unclear how airborne SO2 affects airway hyperresponsiveness (AHR) – a hallmark feature of asthma. To this end, we investigated the effects of chronic exposure to SO2 on AHR, airway inflammation, tissue remodeling, cell stiffness (G′) and contractility of the airway smooth muscle cell (ASMC). Newborn Sprague–Dawley (SD) rats sensitized to ovalbumin (OVA) was used as the model to ...

 

Mechanisms for epigallocatechin gallate induced inhibition of drug metabolizing enzymes in rat liver microsomes

  [CiTO]
Toxicology Letters, Vol. 214, No. 3. (November 2012), pp. 328-338, doi:10.1016/j.toxlet.2012.09.011

Abstract

Epigallocatechin gallate (EGCG) inhibits drug metabolizing enzymes by unknown mechanisms. Here we examined if the inhibition is due to covalent-binding of EGCG to the enzymes or formation of protein aggregates. EGCG was incubated with rat liver microsomes at 1–100 Î¼M for 30 min. The EGCG-binding proteins were affinity purified using m-aminophenylboronic acid agarose and probed with antibodies against glyceraldehyde-3-phosphate dehydrogenase (GAPDH), actin, cytochrome P450 (CYP) 1A1, CYP1A2, CYP2B1/2, CYP2E1, CYP3A, catechol-O-methyltransferase (COMT) and microsomal glutathione transferase 1 (MGST1). All but actin and soluble ...

 

Estrogenic effects and their action mechanism of the major active components of party pill drugs

  [CiTO]
Toxicology Letters, Vol. 214, No. 3. (November 2012), pp. 339-347, doi:10.1016/j.toxlet.2012.09.014

Abstract

Benzylpiperazine (BZP) and trifluoromethylphenylpiperazine (TFMPP) are commonly used constituents of party pill drugs. They are reported to induce psychoactive effects such as euphoria and provide effects similar with other illicit drugs such as methylenedioxymethamphetamine (MDMA). A great deal of evidence has proven that party pills, as alternatives for MDMA, exert harmful effects on users. However, their toxicological effects have not been fully understood and endocrine disruptive effects are still unknown. In this study, we identified estrogenic effects of BZP and TFMPP ...

 

Toxicity effects of short term diesel exhaust particles exposure to human small airway epithelial cells (SAEC) and human lung carcinoma epithelial cells (A549)

  [CiTO]
Toxicology Letters (November 2012), doi:10.1016/j.toxlet.2012.10.016

Abstract

In this study, confocal Raman spectroscopy, atomic force microscope (AFM) and multiplex ELISA were applied to analyze the biophysical responses (biomechanics and biospectroscopy) of normal human primary small airway epithelial cells (SAEC) and human lung carcinoma epithelial A549 cells to in vitro short term DEP exposure (up to 2 hrs). Raman spectra revealed the specific cellular biomolecular changes in cells induced by DEP compared to unexposed control cells. Principal component analysis was successfully applied to analyze spectral differences between control and treated ...

 

Columbamine suppresses the proliferation and neovascularization of metastatic osteosarcoma U2OS cells with low cytotoxicity

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Toxicology Letters (November 2012), doi:10.1016/j.toxlet.2012.10.015

Abstract

Osteosarcoma is one of the most common malignant bone tumors in children and adolescents. Although extensive efforts have been made in anti-osteosarcoma therapy in recent decades, there are no effective low-toxicity drugs for treating patients with metastatic osteosarcoma. Hence, potent anti-metastatic osteosarcoma drugs are highly desired. In this study, we explored novel small molecular anti-metastatic osteosarcoma agents and found that columbamine, an active component of the herb Coptis Chinensis, inhibited the proliferation and neovascularization of metastatic osteosarcoma U2OS cells. Columbamine effectively ...

 

Chemical Safety for Sustainability (CSS): Human in vivo biomonitoring data for complementing results from in vitro toxicology—A commentary

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Toxicology Letters (October 2012), doi:10.1016/j.toxlet.2012.10.011

Abstract

The U.S. Environmental Protection Agency (EPA) has instituted the Chemical Safety for Sustainability (CSS) research program for assessing the health and environmental impact of manufactured chemicals. This is a broad program wherein one of the tasks is to develop high throughput screening (HTS) methods and follow-up confirmation for toxicity at realistic environmental exposure levels. The main tools under this task are in vitro toxicity testing, in silico molecular modeling, and in vivo (systemic) measurements documentation. The in vivo research component is ...

 

A chronic oral exposure of pigs with deoxynivalenol partially prevents the acute effects of lipopolysaccharides on hepatic histopathology and blood clinical chemistry

  [CiTO]
Toxicology Letters (October 2012), doi:10.1016/j.toxlet.2012.10.009

Abstract

Lipopolysaccharides (LPS), a cell wall component of gram-negative bacteria, and deoxynivalenol (DON), a prevalent Fusarium-derived contaminant of cereal grains, are each reported to have detrimental effects on the liver. A potentiating toxic effect of the combined exposure was reported previously in a mouse model and hepatocytes in vitro, but not in swine as the most DON−susceptible species. Thus, pigs were fed either a control diet (CON) or a Fusarium contaminated diet (DON, 3.1 mg DON/kg diet) for 37 days. At day 37 ...

 

Arsenic urinary speciation in Mthfr deficient mice injected with sodium arsenate

  [CiTO]
Toxicology Letters (October 2012), doi:10.1016/j.toxlet.2012.10.014

Abstract

In most mammalian species, arsenic biotransformation occurs primarily by biomethylation and reduction reactions, with dimethylarsinic acid being the predominant metabolite excreted in the urine. Methylenetetrahydrofolate reductase (MTHFR) plays a key role in folate metabolism by channeling one-carbon units between nucleotide synthesis and methylation reactions. In the study on transgenic Mtfhr knockout mice we investigated: (1) whether Mthfr is an important determinant in arsenic biotransformation by performing urinary arsenic speciation, and (2) whether dietary folate deficiency alters arsenic biotransformation in these mice. ...

 

Low pH enhances 2-aminoethoxydiphenyl borate-induced cell death of PC12 cells

  [CiTO]
Toxicology Letters (October 2012), doi:10.1016/j.toxlet.2012.10.013

Abstract

2-Aminoethoxydiphenyl borate (2-APB) is widely used as a pharmacological tool for analysis of cellular Ca2+ regulation. In this study, we found that external acid potentiated neural cell death induced by 2-APB in rat pheochromocytoma 12 (PC12) cells. 2-APB induced cell death in half of the PC12 cells within 30 min at pH 6.6 but not at pH 7.4. The extent of the 2-APB-induced cell death increased in a dose-, time- and pH-dependent manner. Ca2+-imaging revealed that 2-APB increased [Ca2+]i in PC12 cells ...

 

Reproducibility and robustness of metabolome analysis in rat plasma of 28-day repeated dose toxicity studies

  [CiTO]
Toxicology Letters (October 2012), doi:10.1016/j.toxlet.2012.09.015

Abstract

BASF has developed a rat plasma metabolomics database (MetaMap®Tox) containing the metabolome of more than 500 chemicals, agrochemicals and drugs, for which the toxicity is well known, derived from 28-day repeated dose toxicity studies in rats. The quality/reproducibility of data was assessed by comparing the metabolome of 16 reference compounds tested at least twice under identical experimental conditions at three time points (day 7, day 14 and day 28). Statistical correlation analysis showed that the repeated treatment induced very similar changes ...

 

Prooxidative toxicity and selenoprotein suppression by cerivastatin in muscle cells

  [CiTO]
Toxicology Letters (October 2012), doi:10.1016/j.toxlet.2012.10.010

Abstract

Statins are the most widely used drugs for the treatment of hypercholesterolemia. In spite of their overall favorable safety profile, they do possess serious myotoxic potential, whose molecular origin has remained equivocal. Here, we demonstrate in cultivated myoblasts and skeletal muscle cells that cerivastatin at nanomolar concentrations interferes with selenoprotein synthesis and evokes a heightened vulnerability of the cells toward oxidative stressors. A correspondingly increased vulnerability was found with atorvastatin, albeit at higher concentrations than with cerivastatin. In selenium-saturated cells, cerivastatin ...

 

Induction of apoptosis in human breast cancer cells by nimbolide through extrinsic and intrinsic pathway

  [CiTO]
Toxicology Letters (October 2012), doi:10.1016/j.toxlet.2012.10.008

Abstract

We aimed to investigate the cytotoxic effects of nimbolide, a limonoid present in leaves and flowers of the neem tree (Azadirachta indica) on human breast cancer cells. The molecular mechanisms involved in the apoptotic activity exerted by nimbolide were studied on the estrogen dependent (MCF-7) and estrogen independent (MDA-MB-231) human breast cancer cell lines. The growth inhibitory effect of nimbolide was assessed by MTT assay. Apoptosis induction by nimbolide treatment was determined by JC-1 mitochondrial membrane potential staining, cytochrome c release, ...

 

Elevation of intracellular Zn2+ level by nanomolar concentrations of triclocarban in rat thymocytes

  [CiTO]
Toxicology Letters (October 2012), doi:10.1016/j.toxlet.2012.10.012

Abstract

It was recently reported that nanomolar concentrations of triclocarban, an antimicrobial agent, were detected in human blood after the use of soap containing triclocarban. Due to the widespread use of triclocarban in adult and infant personal care products, the report prompted us to study its cytotoxicity. The cytotoxicity of triclocarban was examined in rat thymocytes by using a cytometric technique with propidium iodide for examining cell lethality, FluoZin-3-AM for monitoring the intracellular Zn2+ level, and 5-chloromethylfluorescencein diacetate for estimating the cellular ...

 

Four types of inorganic nanoparticles stimulate the inflammatory reaction in brain microglia and damage neurons in vitro

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Toxicology Letters, Vol. 214, No. 2. (October 2012), pp. 91-98, doi:10.1016/j.toxlet.2012.08.009

Abstract

Once nanoparticles enter the central nervous system (CNS), they immediately encounter a complex environment of resident microglial immune cell and neurons. In the present study, NPs of 20–60 nm in diameter (SiO2-NPs, TiO2-NPs, HAP-NPs and Fe3O4-NPs) were evaluated for their ability to induce microglia-mediated neurodegeneration. The microglia were directly exposed to NPs. The results showed that both TiO2-NPs and HAP-NPs induced significant iNOS expression, resulting in NO release from the microglia. The expression levels of MCP-1 and MIP-1α were also upregulated. These ...

 

The disruption of mitochondrial metabolism and ion homeostasis in chicken hearts exposed to manganese

  [CiTO]
Toxicology Letters, Vol. 214, No. 2. (October 2012), pp. 99-108, doi:10.1016/j.toxlet.2012.08.011

Abstract

Exposure to high levels of manganese (Mn) can result in cardiotoxicity in animals. However, little is known about the effect of excess Mn on poultry hearts. The aim of this study was to investigate the effect of dietary Mn on chicken cardiac injuries and the possible mechanisms of this process. In the present study, 400 fifty-day-old Hy-line brown cocks were randomly divided into four groups, and were fed either a commercial diet (containing 100 mg/kg Mn) or a Mn-supplemented diet containing 600 mg/kg, ...

 

Effects of inhaled nano-TiO2 aerosols showing two distinct agglomeration states on rat lungs

  [CiTO]
Toxicology Letters, Vol. 214, No. 2. (October 2012), pp. 109-119, doi:10.1016/j.toxlet.2012.08.019

Abstract

Nano-aerosols composed of large agglomerates (LA) (>100 nm) are more likely to promote pulmonary clearance via macrophages phagocytosis. Small agglomerates (SA) (<100 nm) seem to escape this first defense mechanism and are more likely to interact directly with biological material. These different mechanisms can influence pulmonary toxicity. This hypothesis was evaluated by comparing the relative pulmonary toxicity induced by aerosolized nano-TiO2 showing two different agglomeration states: SA (<100 nm) and LA (>100 nm) at mass concentrations of 2 or 7 mg/m3. Groups of Fisher 344 male ...

 

Environmental nitrogen dioxide (NO2) exposure influences development and progression of ischemic stroke

  [CiTO]
Toxicology Letters, Vol. 214, No. 2. (October 2012), pp. 120-130, doi:10.1016/j.toxlet.2012.08.021

Abstract

Here the correlativity between NO2, a representative pollutant of vehicle exhaust, and ischemic stroke was first determined under experimental conditions following some epidemiological reports. First, we found that blood viscosity, red blood cell (RBC) aggregation-, electrophoresis- and rigidity-index in healthy rats were increased after exposure to 5 mg/m3 NO2 for one- and three-month. Based on this, we set up stroke rat model and exposed them to NO2 at the same concentration for one week, and found that NO2 exposure time-dependently delayed neurological ...

 

Vasoactive alteration and inflammation induced by polycyclic aromatic hydrocarbons and trace metals of vehicle exhaust particles

  [CiTO]
Toxicology Letters, Vol. 214, No. 2. (October 2012), pp. 131-136, doi:10.1016/j.toxlet.2012.08.012

Abstract

Exposure to particulate matter (PM) increases the incidence of cardiovascular disease, but the underlying mechanisms remain unclear. To characterise ambient PM collected from a coach station in an urban area, particulate polycyclic aromatic hydrocarbons (PAHs) and trace metals were evaluated, and diagnostic ratios were then used to determine the sources based on the PAHs identified in PM. To elucidate the mechanism of PM-induced vascular toxicology, human coronary artery endothelial cells (HCAECs) were exposed to PM, PM-free supernatant and residual PM, and ...

 

Dibenzofuran induces oxidative stress, disruption of trans-mitochondrial membrane potential (ΔΨm) and G1 arrest in human hepatoma cell line

  [CiTO]
Toxicology Letters, Vol. 214, No. 2. (October 2012), pp. 137-144, doi:10.1016/j.toxlet.2012.08.014

Abstract

Dioxins are a class of extremely toxic environmentally persistent pollutant, comprised of halogenated dibenzo-p-dioxins, dibenzofurans and biphenyls. Despite significant human exposure via multiple routes, very little is known about toxicity induced by dibenzofuran (DF). Current study shed lights on the potential toxicity mechanism of DF using human hepatoma cell line (HepG2). It was observed that the exposure to DF potentiate oxidative stress, apoptosis and necrosis at 10 Î¼M within 8 h in HepG2 cells. Interestingly, when we pre-incubated the cells with α-NF (1 nM) ...

 

How benzene and its metabolites affect human marrow derived mesenchymal stem cells

  [CiTO]
Toxicology Letters, Vol. 214, No. 2. (October 2012), pp. 145-153, doi:10.1016/j.toxlet.2012.08.015

Abstract

Benzene is a known environmental pollutant with demonstrated leukemogenic activity. Marrow mesenchymal stem cells (MSCs), contribute to skeletal remodeling and repair. They also support haematopoiesis constructing important elements of haematopoietic niche. In the present study, the effects of a range of benzene concentrations along with those of its reactive metabolites, p-benzoquinone (BQ) and hydroquinone (HQ) on the viability of MSCs, apoptosis induction and caspase3/7 activity in these cells were analyzed. Our findings revealed that low concentrations of these chemicals (10 Î¼M of ...

 

Separating uncertainty and physiological variability in human PBPK modelling: The example of 2-propanol and its metabolite acetone

  [CiTO]
Toxicology Letters, Vol. 214, No. 2. (October 2012), pp. 154-165, doi:10.1016/j.toxlet.2012.08.016

Abstract

Parameter uncertainty and interindividual variability in the predictions of a generic human physiologically based pharmacokinetic (PBPK) model were separated by means of nested Monte Carlo simulations. Separate information on uncertainty and variability can help decision makers to identify whether they should focus on identification of sensitive individuals rather than on additional research to obtain more accurate estimates for particular parameters. In this study, the concentration of acetone in human blood was simulated during and after 4 h of exposure to 2-propanol via ...

 

Effect of garlic-derived organosulfur compounds on mitochondrial function and integrity in isolated mouse liver mitochondria

  [CiTO]
Toxicology Letters, Vol. 214, No. 2. (October 2012), pp. 166-174, doi:10.1016/j.toxlet.2012.08.017

Abstract

The objectives of this work were to evaluate the direct effects of diallysulfide (DAS) and diallyldisulfide (DADS), two major organosulfur compounds of garlic oil, on mitochondrial function and integrity, by using isolated mouse liver mitochondria in a cell-free system. DADS produced concentration-dependent mitochondrial swelling over the range 125–1000 Î¼M, while DAS was ineffective. Swelling experiments performed with de-energized or energized mitochondria showed similar maximal swelling amplitudes. Cyclosporin A (1 Î¼M), or ethylene glycol-bis(2-aminoethylether)-N,N,N′,N′-tetraacetic acid (EGTA, 1 mM) were ineffective in inhibiting DADS-induced mitochondrial swelling. ...

 

Taurine attenuates methamphetamine-induced autophagy and apoptosis in PC12 cells through mTOR signaling pathway

  [CiTO]
Toxicology Letters, Vol. 215, No. 1. (November 2012), pp. 1-7, doi:10.1016/j.toxlet.2012.09.019

Abstract

Methamphetamine (METH), a commonly abused psychostimulant, has been shown to induce neuronal damage by causing reactive oxygen species (ROS) formation, apoptosis and autophagy. Taurine (2-aminoethanesulfonic acid) is involved in several physiological actions in the brain, including neuroprotection, osmoregulation and neurotransmission. In this study, we investigate the protective effect of taurine against METH-induced neurotoxicity in PC12 cells and the underlying mechanism. The results showed that taurine significantly increased the cell viability inhibited by METH. LC3-II expression was elevated by METH treatment, whereas ...

 

Metabolic impacts of high dietary exposure to persistent organic pollutants in mice

  [CiTO]
Toxicology Letters, Vol. 215, No. 1. (November 2012), pp. 8-15, doi:10.1016/j.toxlet.2012.09.022

Abstract

Persistent organic pollutants (POPs) have been linked to metabolic diseases. Yet, the effects of high exposure to dietary POPs remain unclear. We therefore investigated whether elevated exposure to POPs provided by whale meat supplementation could contribute to insulin resistance. C57BL/6J mice were fed control (C) or very high-fat diet (VHF) containing low or high levels of POPs (VHF+POPs) for eight weeks. To elevate the dietary concentrations of POPs, casein was replaced by whale meat containing high levels of pollutants. Feeding VHF+POPs ...

 

Liver X receptor α bidirectionally transactivates human CYP1A1 and CYP1A2 through two cis-elements common to both genes

  [CiTO]
Toxicology Letters, Vol. 215, No. 1. (November 2012), pp. 16-24, doi:10.1016/j.toxlet.2012.09.021

Abstract

CYP1A1 and CYP1A2 are involved in both detoxification and metabolic activation of xenobiotics. Human CYP1A1 (hCYP1A1) and hCYP1A2 exist in a head-to-head orientation in chromosome 15 with the overlapping 5′-flanking region. We have recently reported that nuclear receptor constitutive androstane receptor (CAR), in addition to aryl hydrocarbon receptor, bidirectionally transactivates these genes through common motifs. In this study, we have investigated a role of liver X receptor α (LXRα), another liver-enriched nuclear receptor, in the expression hCYP1A1 and hCYP1A2. In reporter ...

 

Phycocyanin may suppress d-galactose-induced human lens epithelial cell apoptosis through mitochondrial and unfolded protein response pathways

  [CiTO]
Toxicology Letters, Vol. 215, No. 1. (November 2012), pp. 25-30, doi:10.1016/j.toxlet.2012.09.017

Abstract

Apoptosis of lens epithelial cell (LEC) plays an important role in cataract formation, and its prevention may be one of the therapeutic strategies in treating cataract. This study used human lens epithelial cell (hLEC) line SRA01/04 to investigate the protective effect and mechanism of phycocyanin on glactose-induced apoptosis in hLEC. hLECs were cultured in D/F12-10% FBS medium containing 125 mM d-galactose with or without phycocyanin. Cell viability was assessed by methylthiazol tetrazolium (MTT) assay. Cell apoptosis was elevated with Wright–Giemsa staining, AO/EB ...

 

Cytokine expression in trichloroethylene-induced hypersensitivity dermatitis: An in vivo and in vitro study

  [CiTO]
Toxicology Letters, Vol. 215, No. 1. (November 2012), pp. 31-39, doi:10.1016/j.toxlet.2012.09.018

Abstract

The purpose of this study was to address the association between cytokine expression and the hypersensitivity dermatitis induced by trichloroethylene (TCE) exposure. 28 TCE-induced hypersensitivity dermatitis patients, 22 TCE exposed workers and 22 non-exposed controls were enrolled in the study. The serum levels of interleukin (IL)-1β, IL-6, IL-8 and tumor necrosis factor (TNF)-α were analyzed using a magnetic colorbead-based multiplex assay. The patients showed significantly higher levels of serum IL-1β (p = 0.033 and p = 0.015), IL-6 (p < 0.001), IL-8 (p < 0.001 and p = 0.002) and TNF-α ...

 

Caveats of using acetaminophen hepatotoxicity models for natural product testing

  [CiTO]
Toxicology Letters, Vol. 215, No. 1. (November 2012), pp. 40-41, doi:10.1016/j.toxlet.2012.09.023

Abstract

In evaluating the potential of natural products and other chemicals to protect against acetaminophen-induced hepatotoxicity, it is critical to use clinically relevant experimental models and evaluate the initial metabolic activation and protein adduct formation. If these basic principles are not considered, the clinical relevance of the hepatoprotection by a natural product is questionable and conclusions regarding potential mechanisms of protection may be unreliable. Therefore, we feel it is necessary to express our concerns regarding a recent publication by Zhao et al. ...

 

The contribution of human small intestine to chlorpyrifos biotransformation

  [CiTO]
Toxicology Letters, Vol. 215, No. 1. (November 2012), pp. 42-48, doi:10.1016/j.toxlet.2012.09.016

Abstract

Despite the oral intake is the major route of exposure to chlorpyrifos for the general population, few data are available on human intestine biotransformation. In this study the contribution of chlorpyrifos (CPF) metabolism in human small intestine was investigated in microsomes from duodenum (HDM) and ileum/jejunum (HS2M) from 11 individual donors. Samples were characterized for testosterone hydroxylated metabolite formation and CYP content quantification by means of Western blotting. The two methods gave consistent results, evidencing the presence of CY3A4 and its-related ...

 

Potential of the octanol–water partition coefficient (logP) to predict the dermal penetration behaviour of amphiphilic compounds in aqueous solutions

  [CiTO]
Toxicology Letters, Vol. 215, No. 1. (November 2012), pp. 49-53, doi:10.1016/j.toxlet.2012.09.013

Abstract

Aqueous amphiphilic compounds may exhibit enhanced skin penetration compared with neat compounds. Conventional models do not predict this percutaneous penetration behaviour. We investigated the potential of the octanol–water partition coefficient (log P) to predict dermal fluxes for eight compounds applied neat and as 50% aqueous solutions in diffusion cell experiments using human skin. Data for seven other compounds were accessed from literature. In total, seven glycol ethers, three alcohols, two glycols, and three other chemicals were considered. Of these 15 compounds, 10 ...

 

Modifications of the bacterial reverse mutation test reveals mutagenicity of TiO2 nanoparticles and byproducts from a sunscreen TiO2-based nanocomposite

  [CiTO]
Toxicology Letters, Vol. 215, No. 1. (November 2012), pp. 54-61, doi:10.1016/j.toxlet.2012.09.012

Abstract

The bacterial reverse mutation test, recommended by the Organization for Economic Co-operation and Development (OECD) to determine genotoxicity of chemical compounds, has been recently used by several authors to investigate nanoparticles. Surprisingly, test results have been negative, whereas in vitro mammalian cell tests often give positive genotoxic responses. In the present study, we used the fluctuation test procedure with the Salmonella typhimurium strains TA97a, TA98, TA100 and TA102 to determine the mutagenic potential of TiO2 nanoparticles (NP-TiO2) and showed that, when ...

 

Effect of acute aluminum phosphide exposure on rats—A biochemical and histological correlation

  [CiTO]
Toxicology Letters, Vol. 215, No. 1. (November 2012), pp. 62-69, doi:10.1016/j.toxlet.2012.09.020

Abstract

Aluminum phosphide (AlP), a widely used fumigant and rodenticide leads to high mortality if ingested. Its toxicity is due to phosphine liberated when it comes in contact with moisture. The exact mechanism of action of phosphine is not known. In this study male Wistar rats were used. The animals received a single dose (20 mg AlP/kg body weight i.g.) orally. Basic serum biochemical parameters, activity of mitochondrial complexes, antioxidant enzymes and parameters of oxidative stress, individual mitochondrial cytochrome levels were measured along ...

 

Acute toxicant exposure and cardiac autonomic dysfunction from smoking a single narghile waterpipe with tobacco and with a “healthy” tobacco-free alternative

  [CiTO]
Toxicology Letters, Vol. 215, No. 1. (November 2012), pp. 70-75, doi:10.1016/j.toxlet.2012.09.026

Abstract

Tobacco smoking using a waterpipe (narghile, hookah, shisha) has become a global epidemic. Unlike cigarette smoking, little is known about the health effects of waterpipe use. One acute effect of cigarette smoke inhalation is dysfunction in autonomic regulation of the cardiac cycle, as indicated by reduction in heart rate variability (HRV). Reduced HRV is implicated in adverse cardiovascular health outcomes, and is associated with inhalation exposure-induced oxidative stress. Using a 32 participant cross-over study design, we investigated toxicant exposure and effects ...

 

A comparative study of the anticlastogenic effects of chlorophyllin on N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) or 7,12-dimethylbenz (α) anthracene (DMBA) induced micronuclei in mammalian cells in vitro and in vivo

  [CiTO]
Toxicology Letters, Vol. 214, No. 3. (November 2012), pp. 235-242, doi:10.1016/j.toxlet.2012.08.023

Abstract

Chlorophyllin (CHL), a water soluble derivative of chlorophyll has been shown to have both anticarcinogenic and antigenotoxic properties. We evaluated the protective effects of CHL (25 Î¼M in vitro, 4 and 100 mg/kg. b.w.) on the clastogenic action of two model carcinogens, MNNG and DMBA (25 Î¼M and 2 Î¼M respectively) in vitro on human hepatoma cells (HepG2) and (40 mg and 25 mg/Kg/b.w. respectively) in vivo on bone marrow of mice, using the frequencies of induced micronuclei as the end point. Pre-, post- and simultaneous treatments ...

 

Accumulation capacity of primary cultures of adipocytes for PCB-126: Influence of cell differentiation stage and triglyceride levels

  [CiTO]
Toxicology Letters, Vol. 214, No. 3. (November 2012), pp. 243-250, doi:10.1016/j.toxlet.2012.08.018

Abstract

Polychlorinated biphenyls (PCBs) are lipophilic persistent organic chemicals that accumulate at high concentrations in the adipose tissue. Recent studies correlate the presence of such contaminants in fat cells to possible alterations in the regulation of energy homeostasis in adipocytes. As the adipose tissue is composed of adipocytes at several stages of differentiation, it is possible that PCBs already accumulate in cells at an early stage, and thereby impair their development. The exact driving force enabling the massive accumulation of PCBs in ...

 

Silver nanoparticles effects on epididymal sperm in rats

  [CiTO]
Toxicology Letters, Vol. 214, No. 3. (November 2012), pp. 251-258, doi:10.1016/j.toxlet.2012.08.028

Abstract

The motivation of our study was to examine the acute effects of intravenously administered a single bolus dose of silver nanoparticles (AgNPs) on rat spermatogenesis and seminiferous tubules morphology. In the treated rats compared to the vehicle treated control animals, the experiments revealed a size-dependent (20 nm and 200 nm), dose-dependent (5 and 10 mg/kg body mass) and time-dependent (24 h, 7 and 28 days) decrease the epididymal sperm count measured by histological methods. In parallel AgNPs injection increased the level of DNA damage in germ ...

 

Estrogenic effects of fusarielins in human breast cancer cell lines

  [CiTO]
Toxicology Letters, Vol. 214, No. 3. (November 2012), pp. 259-262, doi:10.1016/j.toxlet.2012.09.004

Abstract

The fusarielins are a group of metabolites found in several Aspergillus and Fusarium species that have been reported to have with weak antifungal, antibiotic and cytotoxic effects. This study identifies fusarielin A, F, G and H isolated from Fusarium as mycoestrogens. Mycoestrogens are compounds from fungi that bind to the estrogen receptors and induce an estrogenic response in targeted cells. All four tested fusarielins stimulate MCF-7 cell proliferation with fusarielin H as the most potent, able to stimulate cell proliferation 4-fold ...

 

eNOS gene polymorphisms modify the association of PM10 with oxidative stress

  [CiTO]
Toxicology Letters, Vol. 214, No. 3. (November 2012), pp. 263-267, doi:10.1016/j.toxlet.2012.09.006

Abstract

Previous studies have suggested that air pollution increases various health outcomes through oxidative stress and oxidative stress-related genes modify the relationship between air pollution and health outcomes. Therefore, we evaluated the effect of PM10 on the levels of malondialdehyde (MDA), oxidative stress biomarker, and the effect modification by genetic polymorphisms of eNOS, oxidative stress-related gene, in the 560 Korean elderly. We obtained urine samples repeatedly from participants during five medical examinations between 2008 and 2010 and all ambient air pollutant concentration ...


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