Editors Highlight: Metformin Protects Against Acetaminophen Hepatotoxicity by Attenuation of Mitochondrial Oxidant Stress and Dysfunction
Overdose of acetaminophen (APAP) causes severe liver injury and even acute liver failure in both mice and human. A recent study by Kim et al. (2015, Metformin ameliorates acetaminophen hepatotoxicity via Gadd45β-dependent regulation of JNK signaling in mice. J. Hepatol. 63, 75–82) showed that metformin, a first-line drug to treat type 2 diabetes mellitus, protected against APAP hepatotoxicity in mice. However, its exact protective mechanism has not been well clarified. To investigate this, C57BL/6J mice were treated with 400 mg/kg APAP and 350 mg/kg metformin was given 0.5 h pre- or 2 h post-APAP. Our data showe...
Source: Toxicological Sciences - December 4, 2016 Category: Toxicology Authors: Du, K., Ramachandran, A., Weemhoff, J. L., Chavan, H., Xie, Y., Krishnamurthy, P., Jaeschke, H. Tags: Mechanisms of Metformin Protection Against Acetaminophen Toxicity in Liver Source Type: research
Editors Highlight: Dose-Response Analysis of RNA-Seq Profiles in Archival Formalin-Fixed Paraffin-Embedded Samples
Use of archival resources has been limited to date by inconsistent methods for genomic profiling of degraded RNA from formalin-fixed paraffin-embedded (FFPE) samples. RNA-sequencing offers a promising way to address this problem. Here, we evaluated transcriptomic dose responses using RNA-sequencing in paired FFPE and frozen (FROZ) samples from 2 archival studies in mice, one <2 years old and the other >20 years old. Experimental treatments included 3 different doses of di(2-ethylhexyl)phthalate or dichloroacetic acid for the recently archived and older studies, respectively. Total RNA was ribo-depleted and sequenced ...
Source: Toxicological Sciences - December 4, 2016 Category: Toxicology Authors: Hester, S. D., Bhat, V., Chorley, B. N., Carswell, G., Jones, W., Wehmas, L. C., Wood, C. E. Tags: Use of RNA-Seq in Archival Tissues Source Type: research
A Golden Anniversary for the National Institute of Environmental Health Sciences
(Source: Toxicological Sciences)
Source: Toxicological Sciences - December 4, 2016 Category: Toxicology Authors: Miller, G. W., Aschner, M. Tags: Celebrating 50 Years of NIEHS Source Type: research
From the Editors Desk, Editors Highlights, Letters to the Editor
(Source: Toxicological Sciences)
Source: Toxicological Sciences - December 4, 2016 Category: Toxicology Tags: Look Inside ToxSci Source Type: research
Table of Contents
(Source: Toxicological Sciences)
Source: Toxicological Sciences - December 4, 2016 Category: Toxicology Tags: Standing Material Source Type: research
Subscriptions
(Source: Toxicological Sciences)
Source: Toxicological Sciences - December 4, 2016 Category: Toxicology Tags: Standing Material Source Type: research
Editorial Board
(Source: Toxicological Sciences)
Source: Toxicological Sciences - December 4, 2016 Category: Toxicology Tags: Standing Material Source Type: research
Cover
(Source: Toxicological Sciences)
Source: Toxicological Sciences - December 4, 2016 Category: Toxicology Tags: Cover Source Type: research
MicroRNA Biomarkers of Toxicity in Biological Matrices
(Source: Toxicological Sciences)
Source: Toxicological Sciences - October 27, 2016 Category: Toxicology Authors: Harrill, A. H., McCullough, S. D., Wood, C. E., Kahle, J. J., Chorley, B. N. Tags: Erratum Source Type: research
Arsenite Uncouples Mitochondrial Respiration and Induces a Warburg-Like Effect in Caenorhabditis elegans
(Source: Toxicological Sciences)
Source: Toxicological Sciences - October 27, 2016 Category: Toxicology Authors: Luz, A. T., Godebo, T. R., Bhatt, D. P., Ilkayeva, O. R., Maurer, L. L., Hirschey, M. D., Meyer, J. N. Tags: Corrigenda Source Type: research
Identification of Genes That Modulate Susceptibility to Formaldehyde and Imatinib by Functional Genomic Screening in Human Haploid KBM7 Cells
(Source: Toxicological Sciences)
Source: Toxicological Sciences - October 27, 2016 Category: Toxicology Authors: Shen, H., McHale, C. M., Haider, S. I., Jung, C., Zhang, S., Smith, M. T., Zhang, L. Tags: Corrigenda Source Type: research
From the Cover: Zebrafish Larvae Are Insensitive to Stimulation by Cocaine: Importance of Exposure Route and Toxicokinetics
Zebrafish (Danio rerio) larvae have been suggested as vertebrate model to complement or even replace mammals for rapidly assessing behavioral effects of psychoactive drugs. Yet, divergent responses have been reported in mammals and fish despite the conservation of many drug targets. Cocaine, eg, acts as stimulant in mammals but no such response has been documented for zebrafish larvae. We hypothesized that differences in exposure routes (inhalation or injection in mammals vs waterborne in fish) may be a reason for differences in behavioral responses. We characterized cocaine toxicokinetics by liquid chromatography-mass spe...
Source: Toxicological Sciences - October 27, 2016 Category: Toxicology Authors: Kirla, K. T., Groh, K. J., Steuer, A. E., Poetzsch, M., Banote, R. K., Stadnicka-Michalak, J., Eggen, R. I. L., Schirmer, K., Kraemer, T. Tags: Cocaine Toxicokinetics in Zebrafish Larvae Source Type: research
Identification of Drug-Drug Interactions In Vitro: A Case Study Evaluating the Effects of Sofosbuvir and Amiodarone on hiPSC-Derived Cardiomyocytes
Drug–drug interactions pose a difficult drug safety problem, given the increasing number of individuals taking multiple medications and the relative complexity of assessing the potential for interactions. For example, sofosbuvir-based drug treatments have significantly advanced care for hepatitis C virus-infected patients, yet recent reports suggest interactions with amiodarone may cause severe symptomatic bradycardia and thus limit an otherwise extremely effective treatment. Here, we evaluated the ability of human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) to recapitulate the interaction betwee...
Source: Toxicological Sciences - October 27, 2016 Category: Toxicology Authors: Millard, D. C., Strock, C. J., Carlson, C. B., Aoyama, N., Juhasz, K., Goetze, T. A., Stoelzle-Feix, S., Becker, N., Fertig, N., January, C. T., Anson, B. D., Ross, J. D. Tags: Drug-drug Interactions in Human iPSC-Derived Cardiomyocytes Source Type: research
Editors Highlight: Development of an In vitro Assay Measuring Uterine-Specific Estrogenic Responses for Use in Chemical Safety Assessment
A toxicity pathway approach was taken to develop an in vitro assay using human uterine epithelial adenocarcinoma (Ishikawa) cells as a replacement for measuring an in vivo uterotrophic response to estrogens. The Ishikawa cell was determined to be fit for the purpose of recapitulating in vivo uterine response by verifying fidelity of the biological pathway components and the dose-response predictions to women of child-bearing age. Expression of the suite of estrogen receptors that control uterine proliferation (ERα66, ERα46, ERα36, ERβ, G-protein coupled estrogen receptor (GPER)) were confirmed across...
Source: Toxicological Sciences - October 27, 2016 Category: Toxicology Authors: Miller, M. M., Alyea, R. A., LeSommer, C., Doheny, D. L., Rowley, S. M., Childs, K. M., Balbuena, P., Ross, S. M., Dong, J., Sun, B., Andersen, M. A., Clewell, R. A. Tags: In vitro Assay for Uterine-Specific Actions of Estrogen-Like Compounds Source Type: research
Editors Highlight: Interactive Genotoxicity Induced by Environmentally Relevant Concentrations of Benzo(a)Pyrene Metabolites and Arsenite in Mouse Thymus Cells
Arsenic and polycyclic aromatic hydrocarbon (PAH) exposures affect many people worldwide leading to cancer and other diseases. Arsenite (As+3) and certain PAHs are known to cause genotoxicity. However, there is limited information on the interactions between As+3 and PAHs at environmentally relevant concentrations. The thymus is the primary immune organ for T cell development in mammals. Our previous studies showed that environmentally relevant concentrations of As+3 induce genotoxicity in mouse thymus cells through Poly(ADP-ribose) polymerase (PARP) inhibition. Certain PAHs, such as the metabolites of benzo(a)pyrene (BaP)...
Source: Toxicological Sciences - October 27, 2016 Category: Toxicology Authors: Xu, H., Lauer, F. T., Liu, K. J., Hudson, L. G., Burchiel, S. W. Tags: Genotoxicity of Benzo(a)pyrene and Arsenite Source Type: research
