Table of Contents
(Source: Toxicological Sciences)
Source: Toxicological Sciences - March 27, 2016 Category: Toxicology Tags: Standing Material Source Type: research
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(Source: Toxicological Sciences)
Source: Toxicological Sciences - March 27, 2016 Category: Toxicology Tags: Standing Material Source Type: research
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(Source: Toxicological Sciences)
Source: Toxicological Sciences - March 27, 2016 Category: Toxicology Tags: Standing Material Source Type: research
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(Source: Toxicological Sciences)
Source: Toxicological Sciences - March 27, 2016 Category: Toxicology Tags: Cover Source Type: research
Evaluation of the Relative Performance of Drug-Induced Skeletal Muscle Injury Biomarkers in Rats
Novel skeletal muscle (SKM) injury biomarkers that have recently been identified may outperform or add value to the conventional SKM injury biomarkers aspartate transaminase (AST) and creatine kinase (CK). The relative performance of these novel biomarkers of SKM injury including skeletal troponin I (sTnI), myosin light chain 3 (Myl3), CK M Isoform (Ckm), and fatty acid binding protein 3 (Fabp3) was assessed in 34 rat studies including both SKM toxicants and compounds with toxicities in tissues other than SKM. sTnI, Myl3, Ckm, and Fabp3 all outperformed CK or AST and/or added value for the diagnosis of drug-induced SKM inj...
Source: Toxicological Sciences - February 25, 2016 Category: Toxicology Authors: Burch, P. M., Greg Hall, D., Walker, E. G., Bracken, W., Giovanelli, R., Goldstein, R., Higgs, R. E., King, N. M. P., Lane, P., Sauer, J.-M., Michna, L., Muniappa, N., Pritt, M. L., Vlasakova, K., Watson, D. E., Wescott, D., Zabka, T. S., Glaab, W. E. Tags: Biomarkers of Skeletal Muscle Injury Source Type: research
Cytotoxicity of Thirdhand Smoke and Identification of Acrolein as a Volatile Thirdhand Smoke Chemical That Inhibits Cell Proliferation
This study identified acrolein as a highly cytotoxic VOC in THS which killed cells at high doses and inhibited cell proliferation at low doses. (Source: Toxicological Sciences)
Source: Toxicological Sciences - February 25, 2016 Category: Toxicology Authors: Bahl, V., Weng, N. J.- H., Schick, S. F., Sleiman, M., Whitehead, J., Ibarra, A., Talbot, P. Tags: Acrolein as a Component of Thirdhand Smoke Source Type: research
Screening for Chemical Toxicity Using Cryopreserved Precision Cut Lung Slices
To assess chemical toxicity, current high throughput screening (HTS) assays rely primarily on in vitro measurements using cultured cells. Responses frequently differ from in vivo results due to the lack of physical and humoral interactions provided by the extracellular matrix, cell-cell interactions, and other molecular components of the native organ. To more accurately reproduce organ complexity in HTS, we developed an organotypic assay using the cryopreserved precision cut lung slice (PCLS) from rats and mice. Compared to the never-frozen PCLS, their frozen-thawed counterpart slices showed viability or metaboli...
Source: Toxicological Sciences - February 25, 2016 Category: Toxicology Authors: Watson, C. Y., Damiani, F., Ram-Mohan, S., Rodrigues, S., de Moura Queiroz, P., Donaghey, T. C., Rosenblum Lichtenstein, J. H., Brain, J. D., Krishnan, R., Molina, R. M. Tags: Toxicity Assessment in Cryopreserved Lung Sections Source Type: research
Baseline Chromatin Modification Levels May Predict Interindividual Variability in Ozone-Induced Gene Expression
Traditional toxicological paradigms have relied on factors such as age, genotype, and disease status to explain variability in responsiveness to toxicant exposure; however, these are neither sufficient to faithfully identify differentially responsive individuals nor are they modifiable factors that can be leveraged to mitigate the exposure effects. Unlike these factors, the epigenome is dynamic and shaped by an individual’s environment. We sought to determine whether baseline levels of specific chromatin modifications correlated with the interindividual variability in their ozone (O3)-mediated induction in an air&nda...
Source: Toxicological Sciences - February 25, 2016 Category: Toxicology Authors: McCullough, S. D., Bowers, E. C., On, D. M., Morgan, D. S., Dailey, L. A., Hines, R. N., Devlin, R. B., Diaz-Sanchez, D. Tags: Chromatin Modification and Gene Expression after Ozone Exposure Source Type: research
Low Dose Acetaminophen Induces Reversible Mitochondrial Dysfunction Associated with Transient c-Jun N-Terminal Kinase Activation in Mouse Liver
In conclusion, low dose APAP produces reversible MPT-dependent mitochondrial dysfunction and steatosis in hepatocytes without causing ALT release or necrosis, whereas high dose leads to irreversible mitochondrial dysfunction and cell death associated with sustained JNK activation. Thus, nontoxic APAP has the potential to cause transient mitochondrial dysfunction that may synergize with other stresses to promote liver damage and steatosis. (Source: Toxicological Sciences)
Source: Toxicological Sciences - February 25, 2016 Category: Toxicology Authors: Hu, J., Ramshesh, V. K., McGill, M. R., Jaeschke, H., Lemasters, J. J. Tags: Mitochondrial Effects of Low Dose Acetominophen Source Type: research
The Extended ToxTracker Assay Discriminates Between Induction of DNA Damage, Oxidative Stress, and Protein Misfolding
Chemical exposure of cells may damage biomolecules, cellular structures, and organelles thereby jeopardizing cellular homeostasis. A multitude of defense mechanisms have evolved that can recognize specific types of damaged molecules and will initiate distinct cellular programs aiming to remove the damage inflicted and prevent cellular havoc. As a consequence, quantitative assessment of the activity of the cellular stress responses may serve as a sensitive reporter for the induction of specific types of damage. We have previously developed the ToxTracker assay, a mammalian stem cell-based genotoxicity assay employing two gr...
Source: Toxicological Sciences - February 25, 2016 Category: Toxicology Authors: Hendriks, G., Derr, R. S., Misovic, B., Morolli, B., Calleja, F. M. G. R., Vrieling, H. Tags: Expanded ToxTracker Assay for Genotoxicity Source Type: research
Intrauterine Exposure to Paracetamol and Aniline Impairs Female Reproductive Development by Reducing Follicle Reserves and Fertility
In this study, we investigated the extent to which paracetamol and aniline can interfere with female reproductive development. Intrauterine exposure to paracetamol by gavage of pregnant dams resulted in shortening of the anogenital distance in adult offspring, suggesting that fetal hormone signaling had been disturbed. Female offspring of paracetamol-exposed mothers had ovaries with diminished follicle reserve and reduced fertility. Fetal gonads of exposed animals had also reduced gonocyte numbers, suggesting that the reduced follicle count in adults could be due to early disruption of germ cell development. However, ex vi...
Source: Toxicological Sciences - February 25, 2016 Category: Toxicology Authors: Holm, J. B., Mazaud-Guittot, S., Danneskiold-Samsoe, N. B., Chalmey, C., Jensen, B., Norregard, M. M., Hansen, C. H., Styrishave, B., Svingen, T., Vinggaard, A. M., Koch, H. M., Bowles, J., Koopman, P., Jegou, B., Kristiansen, K., Kristensen, D. M. Tags: Aniline and Acetominophen (Paracetamol) in Female Reproduction Source Type: research
Exposure to p,p'-DDE Alters Macrophage Reactivity and Increases Macrophage Numbers in Adipose Stromal Vascular Fraction
Exposure to p,p'-DDE (DDE), the main bioaccumulative metabolite of the organochlorine insecticide p,p'-DDT, is associated with a higher prevalence of obesity, dyslipidemia, insulin resistance, metabolic syndrome, and immunomodulation. The present study was carried out to determine whether DDE perturbs adipose tissue homeostasis through modulation of macrophage function. Treatment with DDE or a cyclooxygenase-2 inhibitor prior to lipopolysaccharide exposure significantly decreased production of prostaglandins (PG) from J774a.1 macrophages in vitro. Similarly, J774A.1 cell lysates incubated with DDE or a specific cycloo...
Source: Toxicological Sciences - February 25, 2016 Category: Toxicology Authors: Mangum, L. H., Crow, J. A., Stokes, J. V., Howell, G. E., Ross, M. K., Pruett, S. B., Chambers, J. E. Tags: DDE and Macrophage Function Source Type: research
Elevated Nuclear and Cytoplasmic FTY720-Phosphate in Mouse Embryonic Fibroblasts Suggests the Potential for Multiple Mechanisms in FTY720-Induced Neural Tube Defects
This study demonstrates that treatment of LM/Bc mouse embryonic fibroblasts (MEFs) with FTY720 results in a significant accumulation of FTY720-P in both the cytoplasmic and nuclear compartments. Elevated nuclear FTY720-P is associated with decreased HDAC activity and increased histone acetylation at H3K18 and H3K23 in LM/Bc MEFs. Treatment of LM/Bc MEFs with FTY720 and a selective Sphk2 inhibitor, ABC294640, significantly reduces the amount of FTY720-P that accumulates in the nucleus. The data provide insight into the relative amounts of FTY720-P generated in the nuclear versus cytoplasmic subcellular compartments after FT...
Source: Toxicological Sciences - February 25, 2016 Category: Toxicology Authors: Gardner, N. M., Riley, R. T., Showker, J. L., Voss, K. A., Sachs, A. J., Maddox, J. R., Gelineau-van Waes, J. B. Tags: Sphingosine Kinase Phosphorylation of Fingolimod and Neural Tube Defects Source Type: research
Differential Effects of Silver Nanoparticles and Silver Ions on Tissue Accumulation, Distribution, and Toxicity in the Sprague Dawley Rat Following Daily Oral Gavage Administration for 13 Weeks
This study evaluated particulate and ionic forms of silver and particle size for differences in silver accumulation, distribution, morphology, and toxicity when administered daily by oral gavage to Sprague Dawley rats for 13 weeks. Test materials and dose formulations were characterized by transmission electron microscopy (TEM), dynamic light scattering, and inductively coupled mass spectrometry (ICP-MS). Seven-week-old rats (10 rats per sex per group) were randomly assigned to treatments: AgNP (10, 75, and 110 nm) at 9, 18, and 36 mg/kg body weight (bw); silver acetate (AgOAc) at 100, 200, and 400 mg/kg bw; and controls (...
Source: Toxicological Sciences - February 25, 2016 Category: Toxicology Authors: Boudreau, M. D., Imam, M. S., Paredes, A. M., Bryant, M. S., Cunningham, C. K., Felton, R. P., Jones, M. Y., Davis, K. J., Olson, G. R. Tags: Toxicity of Silver Nanoparticles Versus Silver Ions Source Type: research
Multiple Sources of Ca2+ Contribute to Methylmercury-Induced Increased Frequency of Spontaneous Inhibitory Synaptic Responses in Cerebellar Slices of Rat
We previously showed that elevated intracellular Ca2+ ([Ca2+]i) in the molecular layer and granule cells in cerebellar slices is responsible for the initial increases in frequency of spontaneous or miniature inhibitory postsynaptic currents (sIPSCs or mIPSCs) of Purkinje cells following methylmercury (MeHg) treatment. To identify the contribution of different Ca2+ sources to MeHg-induced stimulation of spontaneous GABA release, we examined sIPSC or mIPSC frequency of Purkinje cells in acutely prepared cerebellar slices using whole-cell patch-clamp recording techniques under conditions of lowered [Ca2+]o, pretreatment with ...
Source: Toxicological Sciences - February 25, 2016 Category: Toxicology Authors: Yuan, Y., Atchison, W. D. Tags: Methylmercury and Disrupted Calcium Signaling in Rat Brain Source Type: research
