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Toxicological Sciences: An Official Journal of the Society of Toxicology

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https://www.readbyqxmd.com/read/29688563/prenatal-exposure-to-dehp-induces-neuronal-degeneration-and-neurobehavioral-abnormalities-in-adult-male-mice
#1
Radwa Barakat, Po-Ching Lin, Chan Jin Park, Catherine Best-Popescu, Hatem H Bakery, Mohamed E Abosalum, Nabila M Abdelaleem, Jodi A Flaws, CheMyong Ko
Phthalates are a family of synthetic chemicals that are used in producing a variety of consumer products. Di-(2-ethylhexyl) phthalate (DEHP) is an widely used phthalate and poses a public health concern. Prenatal exposure to DEHP has been shown to induce premature reproductive senescence in animal studies. In this study, we tested the hypothesis that prenatal exposure to DEHP impairs neurobehavior and recognition memory in her male offspring and we investigated one possible mechanism-oxidative damage in the hippocampus...
April 23, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29688525/particulate-matter-triggers-depressive-like-response-associated-with-modulation-of-inflammatory-cytokine-homeostasis-and-brain-derived-neurotrophic-factor-signaling-pathway-in-mice
#2
Xuemei Liu, Xin Qian, Jing Xing, Jinhua Wang, Yixuan Sun, Qin'geng Wang, Huiming Li
Particulate matter (PM) exposure may contribute to depressive-like response in mice. However, few studies have evaluated the adaptive impacts of long-term PM exposure on depressive-like response associated with systemic inflammation and brain-derived neurotrophic factor (BDNF) signaling pathway. We studied the association among depressive-like behaviors, mRNA levels of pro- and anti-inflammatory cytokines, and the expression of BDNF signaling pathway in mice by long-term PM exposure. C57BL/6 male mice were exposed to ambient air alongside control mice breathing air filtered through a high-efficiency air PM (HEPA) filter...
April 23, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29688519/a-possible-novel-mechanism-of-action-of-genistein-and-daidzein-for-activating-thyroid-hormone-receptor-tr-mediated-transcription
#3
Winda Ariyani, Toshiharu Iwasaki, Wataru Miyazaki, Yu Lu, Shigeki Takeda, Noriyuki Koibuchi
Thyroid hormone receptors (TRs) are members of the nuclear receptor superfamily that regulate their target genes for controlling organ development and functional maintenance. Soybean isoflavones, especially genistein and daidzein, modulate various hormone-mediated pathways. However, their effects on TRs have not yet been extensively studied. In this study, the effects of these isoflavones on TR action were evaluated using transient transfection-based reporter gene assays and molecular docking studies. Genistein and daidzein augmented T3-liganded TR-mediated transcription in a concentration-dependent manner...
April 23, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29688484/effect-of-the-catechol-o-methyltransferase-inhibitors-tolcapone-and-entacapone-on-fatty-acid-metabolism-in-heparg-cells
#4
David Grünig, Andrea Felser, Urs Duthaler, Jamal Bouitbir, Stephan Krähenbühl
Tolcapone and entacapone are catechol-O-methyltransferase (COMT) inhibitors used in patients with Parkinson's disease. For tolcapone, patients with liver failure have been reported with microvesicular steatosis observed in the liver biopsy of one patient. We therefore investigated the impact of tolcapone and entacapone on fatty acid metabolism in HepaRG cells exposed for 24 hours and on acutely exposed mouse liver mitochondria. In HepaRG cells, tolcapone induced lipid accumulation starting at 100µM, whereas entacapone was ineffective up to 200µM...
April 23, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29684222/liver-disease-in-a-residential-cohort-with-elevated-polychlorinated-biphenyl-exposures
#5
Heather B Clair, Christina M Pinkston, Shesh N Rai, Marian Pavuk, Nina D Dutton, Guy Brock, Russell A Prough, K Cameron Falkner, Craig J McClain, Matthew C Cave
Endocrine and metabolism disrupting chemicals (EDCs/MDCs) have been associated with environmental liver diseases including toxicant-associated steatohepatitis (TASH). TASH has previously been characterized by hepatocellular necrosis, disrupted intermediary metabolism, and liver inflammation. Polychlorinated biphenyls (PCBs) are environmental EDCs/MDCs associated with the genesis and progression of steatohepatitis in animal models and human liver injury in epidemiology studies. The cross-sectional Anniston Community Health Survey (ACHS) investigates ortho-substituted PCB exposures and health effects near a former PCB manufacturing complex...
April 19, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29684212/cadmium-exposure-of-female-mice-impairs-the-meiotic-maturation-of-oocytes-and-subsequent-embryonic-development
#6
Jia-Qiao Zhu, Yang Liu, Jiang-Hong Zhang, Yan-Fang Liu, Jiang-Qin Cao, Zhu-Tao Huang, Yan Yuan, Jian-Chun Bian, Zong-Ping Liu
Cadmium is one major pollutant that is highly toxic to animals and humans. The mechanism of cadmium toxicity on the female reproductive system, particularly oocyte maturation and fertility, remains to be clarified. In the present study, we used a mouse model to investigate the effects of cadmium in the drinking water on the meiotic maturation of oocytes and subsequent embryonic development, and the underlying mechanisms associated with the impairment of oocyte maturation such as mitochondrial distribution and histone modifications...
April 19, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29669061/zearalenone-delays-rat-leydig-cell-regeneration
#7
Songyi Zhou, Yiyan Wang, Leikai Ma, Xianwu Chen, Yao Lü, Fei Ge, Yong Chen, Xiaofang Chen, Qingquan Lian, Xiao-Dong Jin, Ren-Shan Ge
Zearalenone (ZEA), a fungal mycotoxin, is present in a wide range of human foods. By virtual screening, we have identified that ZEA is a potential endocrine disruptor of Leydig cells. The effect of ZEA on Leydig cell development is still unclear. The objective of the present study was to explore whether ZEA affected Leydig cell developmental process and to clarify the underlying mechanism. Adult male Sprague Dawley rats (60 days old) were randomly divided into three groups and these rats received a single intraperitoneal injection of 75 mg/kg ethane dimethane sulfonate (EDS) to eliminate all Leydig cells...
April 16, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29669094/hydroxylated-graphene-quantum-dots-induce-dna-damage-and-disrupt-microtubule-structure-in-human-esophageal-epithelial-cells
#8
Ming Li, Meng-Meng Gu, Xin Tian, Bei-Bei Xiao, Siyuan Lu, Wei Zhu, Lan Yu, Zeng-Fu Shang
Graphene quantum dots (GQDs) have attracted significant interests due to their unique chemical and physical properties. In the present study, we investigated the potential effects of hydroxyl-modified GQDs (OH-GQDs) on the human esophageal epithelial cell line HET-1A. Our data revealed significant cytotoxicity of OH-GQDs which decreased the viability of HET-1A in a dose and time dependent manner. The moderate concentration (25 or 50 µg/ml) of OH-GQDs significantly blocked HET-1A cells in G0/G1 cell cycle phase...
April 14, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29669060/plasticizer-di-2-ethylhexyl-phthalate-induces-epithelial-to-mesenchymal-transition-and-renal-fibrosis-in-vitro-and-in-vivo
#9
Cheng-Tien Wu, Ching-Chia Wang, Li-Chen Huang, Shing-Hwa Liu, Chih-Kang Chiang
Plasticizer di-(2-ethylhexyl)phthalate (DEHP) is known as an endocrine disruptor and a peroxisome proliferator. A currently epidemiological study has suggested that daily high di-(2-ethylhexyl)phthalate (DEHP) intake from phthalate-tainted foods in children may be a risk factor for renal dysfunction. DEHP can leach from medical devices such as blood storage bags and the tubing. Long-term exposure to DEHP is associated with nephropathy and exacerbates chronic kidney diseases (CKD) progression. However, the detailed effects and molecular mechanisms remain unclear...
April 14, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29669048/metabolomics-on-preadolescent-children-with-high-urinary-bisphenol-a-response-to-dr-williams
#10
Adnan Khan, Youngja H Park
No abstract text is available yet for this article.
April 14, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29669044/polymorphisms-of-arsenic-3-oxidation-state-methyltransferase-and-arsenic-methylation-capacity-affect-the-risk-of-bladder-cancer
#11
Ying-Chin Lin, Wei-Jen Chen, Chao-Yuan Huang, Horng-Sheng Shiue, Chien-Tien Su, Pui-Lam Ao, Yeong-Shiau Pu, Hsueh Yu-Mei
The mechanisms underlying how arsenic methylation capacity affects bladder cancer (BC) are still unclear. The objective of this study was to explore the effects of polymorphisms of arsenic (+3 oxidation state) methyltransferase (AS3MT) on BC risk. We conducted a hospital-based study and enrolled 216 BC and 813 healthy controls from 2007 to 2011. Urinary arsenic profiles were measured using high-performance liquid chromatography-hydride generation-atomic absorption spectrometry. The gene polymorphisms of AS3MT were identified using the Sequenom MassARRAY platform with iPLEX Gold chemistry...
April 14, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29669042/p-glycoprotein-on-blood-brain-barrier-plays-a-vital-role-in-fentanyl-brain-exposure-and-respiratory-toxicity-in-rats
#12
ChenChen Yu, Mei Yuan, HaiYing Yang, XiaoMei Zhuang, Hua Li
Fentanyl is a rapid-acting, short duration opioid analgesic agent. In recent years, increased prescription and illicit use of fentanyl drugs have led to major safety concerns and a growing death toll. However, the causes of fentanyl induced fatal adverse effects have not been thoroughly researched. The current study investigated P-glycoprotein (P-gp) modulated brain blood barrier (BBB) penetration of fentanyl and its resulting toxicity in vitro and in vivo. ATPase assays were performed together with bi-directional transport assays using Caco-2 cells in the presence and absence of tariquidar, a P-gp inhibitor, to confirm the P-gp substrate property of fentanyl...
April 14, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29669109/opposing-actions-of-developmental-trichloroethylene-and-high-fat-diet-co-exposure-on-markers-of-lipogenesis-and-inflammation-in-autoimmune-prone-mice
#13
Sarah J Blossom, Lorenzo Fernandes, Shasha Bai, Sangeeta Khare, Kuppan Gokulan, Youzhong Yuan, Michael Dewall, Frank A Simmen, Kathleen M Gilbert
Trichloroethylene (TCE) is a widespread environmental pollutant associated with immunotoxicity and autoimmune disease. Previous studies showed that mice exposed from gestation through early life demonstrated CD4+ T cell alterations and autoimmune hepatitis. Determining the role of one environmental risk factor for any disease is complicated by the presence of other stressors. Based on its known effects, we hypothesized that developmental overnutrition in the form of a moderately high fat diet (HFD) consisting of 40% kcal fat would exacerbate the immunotoxicity and autoimmune-promoting effects of low-level (<10 μg/kg/day) TCE in autoimmune-prone MRL+/+ mice over either stressor alone...
April 12, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29669021/band-alignment-driven-oxidative-injury-to-the-skin-by-anatase-rutile-mixed-phase-titanium-dioxide-nanoparticles-under-sunlight-exposure
#14
Xiujuan Sun, Yun Chang, Yan Cheng, Yanlin Feng, Haiyuan Zhang
Anatase/rutile mixed-phase titanium dioxide (TiO2) nanoparticles (NPs) have been found in cosmetics and cotton textiles. Once exposed to sunlight, mixed-phase TiO2 NPs are even more toxic to cells than pure phase NPs, however, the underlying mechanism remains unclear. Considering the unique anatase/rutile heterojunction structure existing in mixed-phase NPs, the potent toxicity of mixed-phase TiO2 NPs probably originates from the high reactive oxygen species (ROS) production because the anatase/rutile heterojunction is constituted by the staggered energy bands that facilitate the electron-hole separation at the interface due to the band alignment...
April 12, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29648628/the-serosal-immune-system-of-the-thorax-in-toxicology
#15
C Frieke Kuper, Jolanda van Bilsen, Marcel V W Wijnands
The thoracic cavities receive increasing attention in toxicology, because inhaled fibers and (nano)particles can reach these cavities and challenge the local lymphoid tissues. The thoracic and abdominopelvic cavities are controlled by the serosal immune system with its special, loosely organized lymphoid clusters, namely the fat-associated lymphoid clusters (FALCs) and milky spots, which together can be denoted as serosa-associated lymphoid clusters (SALCs). These clusters house numerous innate lymphoid cells, namely the B1 and ILC2 populations...
April 10, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29635361/central-ikk2-inhibition-ameliorates-air-pollution-mediated-hepatic-glucose-and-lipid-metabolism-dysfunction-in-mice-with-type-ii-diabetes
#16
Qing Sun, Guoqing Zhang, Rucheng Chen, Ran Li, Huanhuan Wang, Apei Jiang, Zhenwei Li, Liya Kong, Laura K Fonken, Sanjay Rajagopalan, Qinghua Sun, Cuiqing Liu
Previous studies supported a role of hypothalamic inflammation in fine ambient particulate matter (PM2.5) exposure-mediated diabetes development. We therefore investigated the effects of PM2.5 exposure on insulin resistance and the disorders of hepatic glucose and lipid metabolism via hypothalamic inflammation. KKAy mice, a genetically susceptible model of Type II diabetes mellitus, were administered intra-cerebroventricularly with IKK2 inhibitor (IMD-0354) and were exposed to either concentrated PM2.5 or filtered air (FA) for four weeks simultaneously via a versatile aerosol concentration exposure system...
April 9, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29660078/respirable-uranyl-vanadate-containing-particulate-matter-derived-from-a-legacy-uranium-mine-site-exhibits-potentiated-cardiopulmonary-toxicity
#17
Katherine E Zychowski, Vamsi Kodali, Molly Harmon, Christina Tyler, Bethany Sanchez, Yoselin Ordonez Suarez, Guy Herbert, Abigail Wheeler, Sumant Avasarala, José M Cerrato, Nitesh K Kunda, Pavan Muttil, Chris Shuey, Adrian Brearley, Abdul-Mehdi Ali, Yan Lin, Mohammad Shoeb, Aaron Erdely, Matthew J Campen
Background: Exposure to windblown particulate matter (PM) arising from legacy uranium (U) mine sites in the Navajo Nation may pose a human health hazard due to their potentially high metal content, including U and vanadium (V). Objective: To assess the toxic impact of PM derived from Claim 28 (a priority U mine) compared to background PM, and consider the putative role of metal species U and V. Methods: Two representative sediment samples from Navajo Nation sites (Background PM and Claim 28 PM) were obtained, characterized in terms of chemistry and morphology, and fractioned to the respirable (≤10μm) fraction...
April 5, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29635646/developmental-exposure-to-aluminum-chloride-irreversibly-affects-postnatal-hippocampal-neurogenesis-involving-multiple-functions-in-mice
#18
Mari Inohana, Ayumi Eguchi, Misato Nakamura, Rei Nagahara, Nobuhiko Onda, Kota Nakajima, Yukie Saegusa, Toshinori Yoshida, Makoto Shibutani
Aluminum (Al) is neurotoxic to adults and also to infants. In this study, we investigated the developmental exposure effect of AlCl3 on postnatal hippocampal neurogenesis. Pregnant mice were administered 0-, 900- or 1800-ppm AlCl3 via drinking water from gestational day 6 to postnatal day (PND) 21, with their offspring examined on PND 21 and PND 77. On PND 21, GFAP-immunoreactive (+) neural stem cells (NSCs) and p21Cip1/Waf1+ cells were decreased in number in the subgranular zone at 900 and ≥ 900 ppm, respectively...
April 4, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29635369/proteomic-comparison-of-various-hepatic-cell-cultures-for-preclinical-safety-pharmacology
#19
Tracey Hurrell, Charis-Patricia Segeritz, Ludovic Vallier, Kathryn S Lilley, Allan Duncan Cromarty
Experimental drugs need to be screened for safety within time constraints. Hepatotoxicity is one concerning contributor to the failure of investigational new drugs and a major rationale for postmarketing withdrawal decisions. Ethical considerations in preclinical research force the requirement for highly predictive in vitro assays using human tissue which retains functionality reflective of primary tissue. Here, the proteome of cells commonly used to assess preclinical hepatotoxicity was compared. Primary human hepatocytes (PHHs), hepatocyte-like cells differentiated from human pluripotent stem cells (HLCs), HepG2 cell monolayers and HepG2 cell three dimensional (3D) spheroids were cultured and collected as whole cell lysates...
April 4, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29617930/impact-of-car-agonist-ligand-tcpobop-on-mouse-liver-chromatin-accessibility
#20
Nicholas J Lodato, Andy Rampersaud, David J Waxman
Activation of the nuclear receptor and transcription factor CAR (Nr1i3) by its specific agonist ligand TCPOBOP (1,4-bis[2-(3,5-dichloropyridyloxy)]benzene) dysregulates hundreds of genes in mouse liver and is linked to male-biased hepatocarcinogenesis. To elucidate the genomic organization of CAR-induced gene responses, we investigated the distribution of TCPOBOP-responsive RefSeq coding and long non-coding RNA (lncRNA) genes across the megabase-scale topologically associating domains (TADs) that segment the genome, and which provide a structural framework that functionally constrains enhancer-promoter interactions...
April 2, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
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