From the Cover: Exposure to Oral Antibiotics Induces Gut Microbiota Dysbiosis Associated with Lipid Metabolism Dysfunction and Low-Grade Inflammation in Mice
Due to a long history of improper and excessive use, Penicillin G (Pen G) and erythromycin (Ery) are regularly detected in environmental samples and pose a great threat to human health. Here, we set out to investigate effects of Pen G, Ery or their mixture on lipid metabolism and gut microbiota in order to better understand their toxicological mechanisms. Male C57BL/6J mice were exposed either to 60 μg/ml Pen G, Ery or a half mixture of both for 6 weeks or to 10 μg/ml Pen G, Ery or a half mixture of both for 14 weeks. In a recovery experiment, male mice were exposed to 60 μg/ml Pen G or Ery for 2 we...
Source: Toxicological Sciences - October 27, 2016 Category: Toxicology Authors: Jin, Y., Wu, Y., Zeng, Z., Jin, C., Wu, S., Wang, Y., Fu, Z. Tags: Antibiotics and Gut Microbiota Dysbiosis Source Type: research
Editors Highlight: Evaluation of a Microelectrode Array-Based Assay for Neural Network Ontogeny Using Training Set Chemicals
Thousands of compounds in the environment have not been characterized for developmental neurotoxicity (DNT) hazard. To address this issue, methods to screen compounds rapidly for DNT hazard evaluation are necessary and are being developed for key neurodevelopmental processes. In order to develop an assay for network formation, this study evaluated effects of a training set of chemicals on network ontogeny by measuring spontaneous electrical activity in neural networks grown on microelectrode arrays (MEAs). Rat (0–24 h old) primary cortical cells were plated in 48 well-MEA plates and exposed to 6 compounds: acetaminop...
Source: Toxicological Sciences - October 27, 2016 Category: Toxicology Authors: Brown, J. P., Hall, D., Frank, C. L., Wallace, K., Mundy, W. R., Shafer, T. J. Tags: Microelectrode Arrays and Neural Networks Source Type: research
From the Cover: Autophagy Induction Contributes to Cadmium Toxicity in Mesenchymal Stem Cells via AMPK/FOXO3a/BECN1 Signaling
This study investigated the role of autophagy in Cd-induced skeleton damage and its potential mechanism. We exposed MSCs to different concentrations of cadmium chloride (3.5, 7, and 14 μM) for 24 h. We demonstrated that Cd treatment increased autophagic flux, and inhibition of autophagic process using BENC1 gene silencing blocked Cd-induced cell death. Cd treatment also significantly increased mRNA levels of various essential autophagy-related genes including ATG5, ATG12, BECN1, LC3, and ULK1. Specifically, Cd increased FOXO3a and FOXO1 expression at the mRNA and protein levels, and AMPK was demonstrated to enhance FOXO...
Source: Toxicological Sciences - October 27, 2016 Category: Toxicology Authors: Yang, M., Pi, H., Li, M., Xu, S., Zhang, L., Xie, J., Tian, L., Tu, M., He, M., Lu, Y., Yu, Z., Zhou, Z. Tags: Cadmium and Autophagy in Mesenchymal Stem Cells Source Type: research
Dietary Route of Exposure for Rabbit Developmental Toxicity Studies
In this study, strategies were employed to optimize rabbit test material consumption via diet. Comparative toxicokinetic profiles of gavage versus dietary administration were evaluated in pregnant or non-pregnant New Zealand White rabbits for 2 novel agrochemicals with different plasma half-lives of elimination (sulfoxaflor, t1/2 = 13.5 h and halauxifen, t1/2 = 1 h). Dietary administration of sulfoxaflor resulted in stable 24-h plasma concentrations, whereas gavage administration resulted in a 3-fold fluctuation in plasma levels between Cmax and Cmin. Dietary administration of sulfoxaflor resulted in a 2-fold higher nomina...
Source: Toxicological Sciences - October 27, 2016 Category: Toxicology Authors: Hannas, B. R., Ellis-Hutchings, R. G., Marshall, V. A., Terry, C., McCoy, A. A., Saghir, S. A., Brooks, K., Eisenbrandt, D., Carney, E. W., Billington, R., Rasoulpour, R. J. Tags: Dietary Exposures to Rabbit Developmental Toxicity Source Type: research
Editors Highlight: Computational Modeling of Plasma Vitellogenin Alterations in Response to Aromatase Inhibition in Fathead Minnows
In vertebrates, conversion of testosterone into 17β-estradiol (E2) is catalyzed by cytochrome P450 (CYP) 19A aromatase. An important role of E2 in oviparous vertebrates such as fish is stimulation of hepatic synthesis of the glycolipoprotein vitellogenin (VTG), an egg yolk precursor essential to oocyte development and larval survival. In fathead minnows (FHMs) (Pimephales promelas) exposed to the aromatase inhibitor fadrozole, plasma VTG levels do not change in concert with plasma E2 levels. Specifically, while plasma VTG and E2 levels both drop quickly when aromatase is first inhibited, the recovery of plasma VTG upo...
Source: Toxicological Sciences - October 27, 2016 Category: Toxicology Authors: Cheng, W.-Y., Zhang, Q., Schroeder, A., Villeneuve, D. L., Ankley, G. T., Conolly, R. Tags: Computational Modeling of Aromatase Inhibition and Plasma Vitellogenin Source Type: research
Effects of Capillary Microsampling on Toxicological Endpoints in Juvenile Rats
Blood sampling during juvenile rat toxicology studies is required to determine the toxicokinetic (TK) profile of compounds. Juvenile rats are too small to undergo repeated blood sampling using conventional methods, which collect 200–300 μl blood at each time point. Recently, capillary microsampling (CMS) gained interest because sample sizes are almost 10 times smaller enabling multi-sample collection from 1 rat. Here, we evaluated the use of CMS in juvenile rats in support of reduced animal usage. Juvenile rats at postnatal day (PND) 4, 10, and 17 underwent CMS via the submandibular, tail, and jugular veins. The C...
Source: Toxicological Sciences - October 27, 2016 Category: Toxicology Authors: Niu, X., Beekhuijzen, M., Schoonen, W., Emmen, H., Wenker, M. Tags: Capillary Microsampling and Toxicological Endpoints Source Type: research
Comparative Developmental Toxicity of Flavonoids Using an Integrative Zebrafish System
Flavonoids are a large, structurally diverse class of bioactive naturally occurring chemicals commonly detected in breast milk, soy based infant formulas, amniotic fluid, and fetal cord blood. The potential for pervasive early life stage exposures raises concerns for perturbation of embryogenesis, though developmental toxicity and bioactivity information is limited for many flavonoids. Therefore, we evaluated a suite of 24 flavonoid and flavonoid-like chemicals using a zebrafish embryo-larval toxicity bioassay—an alternative model for investigating developmental toxicity of environmentally relevant chemicals. Embryos...
Source: Toxicological Sciences - October 27, 2016 Category: Toxicology Authors: Bugel, S. M., Bonventre, J. A., Tanguay, R. L. Tags: Developmental Toxicity of Flavonoids in Zebrafish Source Type: research
Dietary Omega-3 Polyunsaturated Fatty Acids Prevent Vascular Dysfunction and Attenuate Cytochrome P4501A1 Expression by 2,3,7,8-Tetrachlorodibenzo-P-Dioxin
Omega-3 polyunsaturated fatty acids (n-3 PUFAs) found in fish protect against cardiovascular morbidity and mortality; however, many individuals avoid fish consumption due to concerns about pollutants. We tested the hypothesis that n-3 PUFAs would prevent vascular dysfunction induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). C57Bl/6 male mice were fed a chow or n-3 PUFA diet for 10 weeks and were exposed to vehicle or 300 ng/kg/d TCDD during the final 2 weeks on each diet. Aortic vasoconstriction mediated by arachidonic acid (AA) ± SKF525 (P450 inhibitor) or SQ29548 (thromboxane/prostanoid [TP] receptor antagoni...
Source: Toxicological Sciences - October 27, 2016 Category: Toxicology Authors: Wiest, E. F., Walsh-Wilcox, M. T., Rothe, M., Schunck, W.-H., Walker, M. K. Tags: Dietary Omega-3 PUFAs and TCDD Vascular Dysfunction Source Type: research
From the Cover: Ethylmercury-Induced Oxidative and Endoplasmic Reticulum Stress-Mediated Autophagic Cell Death: Involvement of Autophagosome-Lysosome Fusion Arrest
In this study, EtHg-induced toxicity and autophagy in the mouse kidney was observed and then the mechanism of toxicity was explored in vitro in HK-2 cells. Low doses of EtHg induced autophagy without causing any histopathological changes in mouse kidneys. However, mice treated with high doses of EtHg exhibited severe focal tubular cell necrosis of the proximal tubules with autophagy. EtHg dose-dependently increased the production of reactive oxygen species, reduced the mitochondrial membrane potential, activated the unfolded protein response, and increased cytosolic Ca2+ levels in HK-2 cells. Cell death induced by EtHg exp...
Source: Toxicological Sciences - October 27, 2016 Category: Toxicology Authors: Choi, J.-Y., Won, N.-H., Park, J.-D., Jang, S., Eom, C.-Y., Choi, Y., Park, Y. I., Dong, M.-S. Tags: Ethylmercury and Autophagic Cell Death Source Type: research
Boric Acid Is Reproductively Toxic to Adult Xenopus laevis, but Not Endocrine Active
The potential reproductive and endocrine toxicity of boric acid (BA) in the African clawed frog, Xenopus laevis, was evaluated using a 30-day exposure of adult frogs. Adult female and male frogs established as breeders were exposed to a culture water control and 4 target (nominal) test concentrations [5.0, 7.5, 10.0, and 15 mg boron (B)/L, equivalent to 28.5, 42.8, 57.0, and 85.5 mg BA/L] using flow-through diluter exposure system. The primary endpoints measured were adult survival, growth (weight and snout-vent length [SVL]), necropsy data, reproductive fecundity, and development of progeny (F1) from the exposed frogs. Ne...
Source: Toxicological Sciences - October 27, 2016 Category: Toxicology Authors: Fort, D. J., Fort, T. D., Mathis, M. B., Ball, R. W. Tags: Reproductive Toxicity of Boric Acid Source Type: research
Effect of Repeated Daily Dosing with 2,4-Dinitrochlorobenzene on Glutathione Biosynthesis and Nrf2 Activation in Reconstructed Human Epidermis
Glutathione (GSH) plays a major role in skin detoxification processes due to its ability to conjugate electrophilic exogenous compounds with, and sometimes without, catalysis by glutathione-s-transferase (GST). GST activity has been demonstrated both in skin and in most in vitro skin equivalents but so far studies have focussed on chemical clearance (conjugate identification and rate of conjugation) and did not consider the GSH lifecycle (conjugation, recycling, synthesis). We used the model skin sensitizer 2,4-dinitrochlorobenzene (DNCB) to investigate the effects of chemical exposure on GSH lifecycle in reconstructed hum...
Source: Toxicological Sciences - October 27, 2016 Category: Toxicology Authors: Spriggs, S., Sheffield, D., Olayanju, A., Kitteringham, N. R., Naisbitt, D. J., Aleksic, M. Tags: 2,4-Dinitrochlorobenzene and NRF2 Activation in Human Epidermis Source Type: research
Table of Contents
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Source: Toxicological Sciences - October 27, 2016 Category: Toxicology Tags: Standing Material Source Type: research
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Editorial Board
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Source: Toxicological Sciences - October 27, 2016 Category: Toxicology Tags: Standing Material Source Type: research
Cover
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Source: Toxicological Sciences - October 27, 2016 Category: Toxicology Tags: Cover Source Type: research
