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Toxicology Reports

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https://www.readbyqxmd.com/read/27158593/arsenic-inhibits-stem-cell-differentiation-by-altering-the-interplay-between-the-wnt3a-and-notch-signaling-pathways
#1
Lisa J Bain, Jui-Tung Liu, Ryan E League
Millions of people are exposed to arsenic through their drinking water and food, but the mechanisms by which it impacts embryonic development are not well understood. Arsenic exposure during embryogenesis is associated with neurodevelopmental effects, reduced weight gain, and altered locomotor activity, and in vitro data indicates that arsenic exposure inhibits stem cell differentiation. This study investigated whether arsenic disrupted the Wnt3a signaling pathway, critical in the formation of myotubes and neurons, during the differentiation in P19 mouse embryonic stem cells...
2016: Toxicology Reports
https://www.readbyqxmd.com/read/26942110/hypercholesterolemia-with-consumption-of-pfoa-laced-western-diets-is-dependent-on-strain-and-sex-of-mice
#2
Sandra L Rebholz, Thomas Jones, Robert L Herrick, Changchun Xie, Antonia M Calafat, Susan M Pinney, Laura A Woollett
Perfluorooctanoic acid (PFOA) is a man-made surfactant with a number of industrial applications. It has a long half-life environmentally and biologically. Past studies suggest a direct relationship between plasma cholesterol and PFOA serum concentrations in humans and an inverse one in rodents fed standard rodent chow, making it difficult to examine mechanisms responsible for the potential PFOA-induced hypercholesterolemia and altered sterol metabolism. To examine dietary modification of PFOA-induced effects, C57BL/6 and BALB/c mice were fed PFOA in a fat- and cholesterol-containing diet...
2016: Toxicology Reports
https://www.readbyqxmd.com/read/26770886/metallothionein-s-role-in-pcb126-induced-hepatotoxicity-and-hepatic-micronutrient-disruption
#3
W D Klaren, S Flor, K N Gibson-Corley, G Ludewig, L W Robertson
Polychlorinated biphenyls (PCBs), industrial chemicals and persistent environmental pollutants, are found in rural and urban settings. Rodent studies have shown that exposure to PCB126, a dioxin-like PCB, causes a significant disruption of hepatic micronutrient homeostasis and an increase in metallothionein (MT), an antioxidant protein and metal carrier. A MT knockout mouse strain was used to assess metallothionein's role in micronutrient disruption and overall hepatotoxicity. Twenty four 129S male mice (12 wild type (WT) and 12 MT knockout (MTKO)) were placed on a purified diet (AIN-93G) for 3 weeks to achieve hepatic metal equilibrium...
2016: Toxicology Reports
https://www.readbyqxmd.com/read/26722641/sequencing-the-exposome-a-call-to-action
#4
Dean P Jones
The exposome is a complement to the genome that includes non-genetic causes of disease. Multiple definitions are available, with salient points being global inclusion of exposures and behaviors, and cumulative integration of associated biologic responses. As such, the concept is both refreshingly simple and dauntingly complex. This article reviews high-resolution metabolomics (HRM) as an affordable approach to routinely analyze samples for a broad spectrum of environmental chemicals and biologic responses. HRM has been successfully used in multiple exposome research paradigms and is suitable to implement in a prototype universal exposure surveillance system...
2016: Toxicology Reports
https://www.readbyqxmd.com/read/26855884/sex-dependent-effects-of-developmental-arsenic-exposure-on-methylation-capacity-and-methylation-regulation-of-the-glucocorticoid-receptor-system-in-the-embryonic-mouse-brain
#5
Andrea M Allan, Alexander K Hafez, Matthew T Labrecque, Elizabeth R Solomon, M Nabil Shaikh, Xianyun Zheng, Abdulmehdi Ali
Previously we have shown that prenatal moderate arsenic exposure (50 ppb) disrupts glucocorticoid receptor (GR) programming and that these changes continue into adolescence in males. However, it was not clear what the molecular mechanisms were promoting these GR programming changes or if these changes occurred in arsenic-exposed females. In the present studies, we assessed the effects of arsenic on protein and mRNA of the glucocorticoid receptor (GR) and 11β-hydroxysteroid dehydrogenase (Hsd) isozymes and compared the levels of methylation within the promoters of the Nr3c1 and Hsd11b1 genes in female fetal brain at embryonic days (E) 14 and 18...
October 2015: Toxicology Reports
https://www.readbyqxmd.com/read/26726309/protective-effects-of-novel-organic-selenium-compounds-against-oxidative-stress-in-the-nematode-caenorhabditis-elegans
#6
Sílvio Terra Stefanello, Priscila Gubert, Bruna Puntel, Caren Rigon Mizdal, Marli Matiko Anraku de Campos, Syed M Salman, Luciano Dornelles, Daiana Silva Avila, Michael Aschner, Félix Alexandre Antunes Soares
Organic selenium compounds possess numerous biological properties, including antioxidant activity. Yet, the high toxicity of some of them, such as diphenyl diselenide (DPDS), is a limiting factor in their current usage. Accordingly, we tested four novel organic selenium compounds in the non-parasite nematode Caenorhabditis elegans and compared their efficacy to DPDS. The novel organic selenium compounds are β-selenoamines (1-phenyl-3-(p-tolylselanyl)propan-2-amine (C1) and 1-(2-methoxyphenylselanyl)-3-phenylpropan-2-amine (C2) and analogs of DPDS (1,2-bis (2-methoxyphenyl) diselenide (C3) and 1,2-bisp-tolyldiselenide (C4)...
2015: Toxicology Reports
https://www.readbyqxmd.com/read/26705515/preclinical-rodent-toxicity-studies-for-long-term-use-of-ceftriaxone
#7
Elena Ratti, James D Berry, David J Greenblatt, Lorena Loci, Amy Swartz Ellrodt, Jeremy M Shefner, Merit E Cudkowicz
A 6-month rodent toxicology and pharmacokinetic (PK) study was performed to provide supportive safety data for long-term use of intravenous ceftriaxone in a clinical trial in patients with amyotrophic lateral sclerosis (ALS). Ceftriaxone was administered by subcutaneous injection at up to 2 g/kg/day to Sprague-Dawley Crl:CD (SD) rats. Ceftriaxone was found to be safe and well tolerated. Specifically, no significant differences in body weight and food consumption were observed between the treatment and control groups...
2015: Toxicology Reports
https://www.readbyqxmd.com/read/26295019/effects-of-developmental-exposure-to-manganese-and-or-low-iron-diet-changes-to-metal-transporters-sucrose-preference-elevated-zero-maze-open-field-and-locomotion-in-response-to-fenfluramine-amphetamine-and-mk-801
#8
Robyn M Amos-Kroohs, Colin P Bloor, Momina A Qureshi, Charles V Vorhees, Michael T Williams
Manganese overexposure (MnOE) can be neurotoxic. In humans this can occur through occupational exposure, air or water contamination, well water, soy milk, and some baby formulas. In children MnOE has been associated with cognitive and behavioral deficits. The effects of MnOE may be modified by factors such as iron status. We hypothesized that developmental MnOE would be exacerbated by iron deficiency. A diet with a 90% decrease in iron (FeD) was given to gravid female rats starting on embryonic day 15 and continued through postnatal day (P)28...
2015: Toxicology Reports
https://www.readbyqxmd.com/read/26213685/the-use-of-urinary-and-kidney-silam-proteomics-to-monitor-kidney-response-to-high-dose-morpholino-oligonucleotides-in-the-mdx-mouse
#9
Aiping Zhang, Kitipong Uaesoontrachoon, Conner Shaughnessy, Jharna R Das, Sree Rayavarapu, Kristy J Brown, Patricio E Ray, Kanneboyina Nagaraju, John N van den Anker, Eric P Hoffman, Yetrib Hathout
Phosphorodiamidate morpholino oligonucleotides (PMO) are used as a promising exon-skipping gene therapy for Duchenne Muscular Dystrophy (DMD). One potential complication of high dose PMO therapy is its transient accumulation in the kidneys. Therefore new urinary biomarkers are needed to monitor this treatment. Here, we carried out a pilot proteomic profiling study using stable isotope labeling in mammals (SILAM) strategy to identify new biomarkers to monitor the effect of PMO on the kidneys of the dystrophin deficient mouse model for DMD (mdx-23)...
2015: Toxicology Reports
https://www.readbyqxmd.com/read/26167454/determination-of-maximum-tolerated-dose-and-toxicity-of-inauhzin-in-mice
#10
Qi Zhang, Shelya X Zeng, Hua Lu
Reactivating the tumor suppressor p53 offers an attractive strategy for developing cancer therapy. We recently identified Inauhzin (INZ) as a novel non-genotoxic p53-activating compound. To develop INZ into a clinically applicable anticancer drug, we have initiated preclinical toxicity studies. Here, we report our study on determining the maximum tolerated dose (MTD) of INZ analog, Inauhzin-C (INZ (C)), following intraperitoneal (i.p) administration (Phase A) and its toxicity following i.p administration over a period of 5-day dosing plus 2-day recovery (Phase B) in CD-1 mice...
2015: Toxicology Reports
https://www.readbyqxmd.com/read/26029632/comparative-metal-oxide-nanoparticle-toxicity-using-embryonic-zebrafish
#11
Leah C Wehmas, Catherine Anders, Jordan Chess, Alex Punnoose, Cliff B Pereira, Juliet A Greenwood, Robert L Tanguay
Engineered metal oxide nanoparticles (MO NPs) are finding increasing utility in the medical field as anticancer agents. Before validation of in vivo anticancer efficacy can occur, a better understanding of whole-animal toxicity is required. We compared the toxicity of seven widely used semiconductor MO NPs made from zinc oxide (ZnO), titanium dioxide, cerium dioxide and tin dioxide prepared in pure water and in synthetic seawater using a five-day embryonic zebrafish assay. We hypothesized that the toxicity of these engineered MO NPs would depend on physicochemical properties...
2015: Toxicology Reports
https://www.readbyqxmd.com/read/25932382/comparison-of-anorectic-potencies-of-the-trichothecenes-t-2-toxin-ht-2-toxin-and-satratoxin-g-to-the-ipecac-alkaloid-emetine
#12
Wenda Wu, Hui-Ren Zhou, Xiao Pan, James J Pestka
Trichothecene mycotoxins, potent translational inhibitors that are associated with human food poisonings and damp-building illnesses, are of considerable concern to animal and human health. Food refusal is a hallmark of exposure of experimental animals to deoxynivalenol (DON) and other Type B trichothecenes but less is known about the anorectic effects of foodborne Type A trichothecenes (e.g., T-2 toxin, HT-2 toxin), airborne Type D trichothecenes (e.g. satratoxin G [SG]) or functionally analogous metabolites that impair protein synthesis...
2015: Toxicology Reports
https://www.readbyqxmd.com/read/25859428/prolongation-of-chemically-induced-methemoglobinemia-in-mice-lacking-%C3%AE-synuclein-a-novel-pharmacologic-and-toxicologic-phenotype
#13
Yien-Ming Kuo, Robert L Nussbaum
The protein α -synuclein is considered central to the pathogenesis of Parkinson disease (PD) on genetic and histopathological grounds. It is widely expressed in fetal life and continues to be highly expressed in adult neural tissues, red blood cells and platelets, while the remainder of adult tissues are reported to have little or no expression. Despite cellular and molecular evidence for a role in neuronal function including synaptic vesicle trafficking, neurotransmitter release, mitochondrial function, lipid metabolism, neurogenesis, neuroprotection, and neuromelanin biosynthesis, mice ablated for the gene encoding α -synuclein (Snca) have little or no neurological phenotype...
2015: Toxicology Reports
https://www.readbyqxmd.com/read/25170436/cadmium-alters-the-formation-of-benzo-a-pyrene-dna-adducts-in-the-rptec-tert1-human-renal-proximal-tubule-epithelial-cell-line
#14
Bridget R Simon, Mark J Wilson, Diane A Blake, Haini Yu, Jeffrey K Wickliffe
Previously, we demonstrated the sensitivity of RPTEC/TERT1 cells, an immortalized human renal proximal tubule epithelial cell line, to two common environmental carcinogens, cadmium (Cd) and benzo[a]pyrene (B[a]P). Here, we measured BPDE-DNA adducts using a competitive ELISA method after cells were exposed to 0.01, 0.1, and 1 μM B[a]P to determine if these cells, which appear metabolically competent, produce BPDE metabolites that react with DNA. BPDE-DNA adducts were most significantly elevated at 1 μM B[a]P after 18 and 24 hours with 36...
July 14, 2014: Toxicology Reports
https://www.readbyqxmd.com/read/27722094/transcriptome-metabolome-wide-association-study-tmwas-of-maneb-and-paraquat-neurotoxicity-reveals-network-level-interactions-in-toxicologic-mechanism
#15
James R Roede, Karan Uppal, Youngja Park, ViLinh Tran, Dean P Jones
A combination of the herbicide paraquat (PQ) and fungicide maneb (MB) has been linked to Parkinson's disease. Previous studies show that this involves an additive toxicity with at least two different mechanisms. However, detailed understanding of mixtures is often difficult to elucidate because of the multiple ways by which toxic agents can interact. In the present study, we used a combination of transcriptomics and metabolomics to investigate mechanisms of toxicity of PQ and MB in a neuroblastoma cell line...
2014: Toxicology Reports
https://www.readbyqxmd.com/read/26877973/quantitation-of-4-4-methylene-diphenyl-diisocyanate-human-serum-albumin-adducts
#16
Leah G Luna, Brett J Green, Fagen Zhang, Scott M Arnold, Paul D Siegel, Michael J Bartels
4,4'-Methylene diphenyl diisocyanate (herein 4,4'-MDI) is used in the production of polyurethane foams, elastomers, coatings, adhesives and the like for a wide range of commercial products. Occupational exposure to MDI levels above current airborne exposure limits can elicit immune mediated hypersensitivity reactions such as occupational asthma in sensitive individuals. To accurately determine exposure, there has been increasing interest in developing analytical methods to measure internal biomarkers of exposure to MDI...
2014: Toxicology Reports
https://www.readbyqxmd.com/read/25621204/custom-mentholation-of-commercial-cigarettes-for-research-purposes
#17
Ian C MacGregor, Stephen B Stanfill, Sydney M Gordon, Douglas J Turner, Jenny M Butler, Elizabeth A Hanft, Hyoshin Kim, Robyn R Kroeger, Marielle C Brinkman, Margaret E Tefft, Pamela I Clark, Stephanie S Buehler
In the U.S. menthol remains the sole permitted characterizing cigarette flavor additive in part because efforts to link menthol cigarette use to increased tobacco-related disease risk have been inconclusive. To perform definitive studies, cigarettes that differ only in menthol content are required, yet these are not commercially available. We prepared research cigarettes differing only in menthol content by deposition of L-menthol vapor directly onto commercial nonmenthol cigarettes, and developed a method to measure a cigarette's menthol and nicotine content...
January 1, 2014: Toxicology Reports
https://www.readbyqxmd.com/read/25574457/effects-of-developmental-manganese-stress-and-the-combination-of-both-on-monoamines-growth-and-corticosterone
#18
Charles V Vorhees, Devon L Graham, Robyn M Amos-Kroohs, Amanda A Braun, Curtis E Grace, Tori L Schaefer, Matthew R Skelton, Keith M Erikson, Michael Aschner, Michael T Williams
Developmental exposure to manganese (Mn) or stress can each be detrimental to brain development. Here, Sprague-Dawley rats were exposed to two housing conditions and Mn from postnatal day (P)4-28. Within each litter two males and 2 females were assigned to the following groups: 0 (vehicle), 50, or 100 mg/kg Mn by oral gavage every other day. Half the litters were reared in cages with standard bedding and half with no bedding. One pair/group in each litter had an acute shallow water stressor before tissue collection (i...
2014: Toxicology Reports
https://www.readbyqxmd.com/read/25530946/sustained-expression-of-cyps-and-dna-adduct-accumulation-with-continuous-exposure-to-pcb126-and-pcb153-through-a-new-delivery-method-polymeric-implants
#19
Farrukh Aqil, Hua Shen, Jeyaprakash Jeyabalan, Xing Xin, Hans-Joachim Lehmler, Gabriele Ludewig, Larry W Robertson, Ramesh C Gupta
A new delivery method via polymeric implants was used for continuous exposure to PCBs. Female Sprague-Dawley rats received subcutaneous polymeric implants containing PCB126 (0.15% load), PCB153 (5% load), or both, for up to 45 days and release kinetics and tissue distribution were measured. PCB153 tissue levels on day 15 were readily detected in lung, liver, mammary and serum, with highest levels in the mammary tissue. PCB126 was detected only in liver and mammary tissues. However, a completely different pharmacokinetics was observed on co-exposure of PCB153 and PCB126, with a 1...
January 1, 2014: Toxicology Reports
https://www.readbyqxmd.com/read/25530945/piperlongumine-induces-pancreatic-cancer-cell-death-by-enhancing-reactive-oxygen-species-and-dna-damage
#20
Harsharan Dhillon, Shireen Chikara, Katie M Reindl
Pancreatic cancer is one of the most deadly cancers with a nearly 95% mortality rate. The poor response of pancreatic cancer to currently available therapies and the extremely low survival rate of pancreatic cancer patients point to a critical need for alternative therapeutic strategies. The use of reactive oxygen species (ROS)-inducing agents has emerged as an innovative and effective strategy to treat various cancers. In this study, we investigated the potential of a known ROS inducer, piperlongumine (PPLGM), a bioactive agent found in long peppers, to induce pancreatic cancer cell death in cell culture and animal models...
2014: Toxicology Reports
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