Toxicology Commons^™

Influences Of Quality Of Maternal Care And Environmental Enrichment On Associative Memory Function In Rats With Early Life Lead Exposure, Jay S. Schneider, Courtney Williams, Shamaila Zafar, Jaehyun Joo, Blanca E. Himes

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

INTRODUCTION: Children in low socioeconomic status (SES) communities are at higher risk of exposure to lead (Pb) and potentially more severe adverse outcomes from Pb exposures. While the factors encompassing SES are complex, low SES households often have less enriching home environments and parent-child interactions. This study investigated the extent to which environmental/behavioral factors (quality of maternal care and richness of the postnatal environment) may modify adverse effects from Pb exposure.

METHODS: Long-Evans female rats were randomly assigned to Control (no Pb), Early Postnatal (EPN: birth through weaning), or Perinatal (PERI: 14 days pre-mating through weaning) Pb exposure groups. From …

Protecting Human And Animal Health: The Road From Animal Models To New Approach Methods, Barbara L F Kaplan, Alan M Hoberman, William Slikker, Mary Alice Smith, Emanuela Corsini, Thomas B Knudsen, M Sue Marty, Sonya K Sobrian, Suzanne C Fitzpatrick, Marcia H Ratner, Donna L Mendrick

Faculty, Staff and Student Publications

Animals and animal models have been invaluable for our current understanding of human and animal biology, including physiology, pharmacology, biochemistry, and disease pathology. However, there are increasing concerns with continued use of animals in basic biomedical, pharmacological, and regulatory research to provide safety assessments for drugs and chemicals. There are concerns that animals do not provide sufficient information on toxicity and/or efficacy to protect the target population, so scientists are utilizing the principles of replacement, reduction, and refinement (the 3Rs) and increasing the development and application of new approach methods (NAMs). NAMs are any technology, methodology, approach, or assay used …

Natural Sources And Bioactivities Of 2,4-Di-Tert-Butylphenol And Its Analogs, Fuqiang Zhao, Ping Wang, Rima D. Lucardi, Zushang Su, Shiyou Li

NCPC Publications and Patents

2,4-Di-tert-butylphenol or 2,4-bis(1,1-dimethylethyl)-phenol (2,4-DTBP) is a common toxic secondary metabolite produced by various groups of organisms. The biosources and bioactivities of 2,4-DTBP have been well investigated, but the phenol has not been systematically reviewed. This article provides a comprehensive review of 2,4-DTBP and its analogs with emphasis on natural sources and bioactivities. 2,4-DTBP has been found in at least 169 species of bacteria (16 species, 10 families), fungi (11 species, eight families), diatom (one species, one family), liverwort (one species, one family), pteridiphyta (two species, two families), gymnosperms (four species, one family), dicots (107 species, 58 families), monocots (22 species, …

Inhibition Of Post-Transcriptional Steps In Ribosome Biogenesis Confers Cytoprotection Against Chemotherapeutic Agents In A P53-Dependent Manner, Russell T Sapio, Anastasiya N Nezdyur, Matthew Krevetski, Leonid Anikin, Vincent J Manna, Natalie Minkovsky, Dimitri G Pestov

Rowan-Virtua School of Osteopathic Medicine Departmental Research

The p53-mediated nucleolar stress response associated with inhibition of ribosomal RNA transcription was previously shown to potentiate killing of tumor cells. Here, we asked whether targeting of ribosome biogenesis can be used as the basis for selective p53-dependent cytoprotection of nonmalignant cells. Temporary functional inactivation of the 60S ribosome assembly factor Bop1 in a 3T3 cell model markedly increased cell recovery after exposure to camptothecin or methotrexate. This was due, at least in part, to reversible pausing of the cell cycle preventing S phase associated DNA damage. Similar cytoprotective effects were observed after transient shRNA-mediated silencing of Rps19, but not …

A Compromised Liver Alters Polychlorinated Biphenyl-Mediated Toxicity, Banrida Wahlang, Jordan T. Perkins, Michael C. Petriello, Jessie B. Hoffman, Arnold J. Stromberg, Bernhard Hennig

Superfund Research Center Faculty Publications

Exposure to environmental toxicants namely polychlorinated biphenyls (PCBs) is correlated with multiple health disorders including liver and cardiovascular diseases. The liver is important for both xenobiotic and endobiotic metabolism. However, the responses of an injured liver to subsequent environmental insults has not been investigated. The current study aims to evaluate the role of a compromised liver in PCB-induced toxicity and define the implications on overall body homeostasis. Male C57Bl/6 mice were fed either an amino acid control diet (CD) or a methionine-choline deficient diet (MCD) during the 12-week study. Mice were subsequently exposed to either PCB126 (4.9 mg/kg) or the …

Comparison Of Protein Phosphatase Inhibition Assay With Lc-Ms/Ms For Diagnosis Of Microcystin Toxicosis In Veterinary Cases, Caroline E. Moore, Jeanette Juan, Yanping Lin, Cynthia L. Gaskill, Birgit Puschner

Veterinary Diagnostic Laboratory Faculty Publications

Microcystins are acute hepatotoxins of increasing global concern in drinking and recreational waters and are a major health risk to humans and animals. Produced by cyanobacteria, microcystins inhibit serine/threonine protein phosphatase 1 (PP1). A cost-effective PP1 assay using p-nitrophenyl phosphate was developed to quickly assess water and rumen content samples. Significant inhibition was determined via a linear model, which compared increasing volumes of sample to the log-transformed ratio of the exposed rate over the control rate of PP1 activity. To test the usefulness of this model in diagnostic case investigations, samples from two veterinary cases were tested. In August …

Distribution, Elimination, And Biopersistence To 90 Days Of A Systemically Introduced 30 Nm Ceria-Engineered Nanomaterial In Rats, Robert A. Yokel, Tu C. Au, Robert Macphail, Sarita S. Hardas, D. Allan Butterfield, Rukhsana Sultana, Michael Goodman, Michael T. Tseng, Mo Dan, Hamed Haghnazar, Jason M. Unrine, Uschi M. Graham, Peng Wu, Eric A. Grulke

Pharmaceutical Sciences Faculty Publications

Nanoceria is used as a catalyst in diesel fuel, as an abrasive in printed circuit manufacture, and is being pursued as an antioxidant therapeutic. Our objective is to extend previous findings showing that there were no reductions of cerium in organs of the mononuclear phagocyte (reticuloendothelial) system up to 30 days after a single nanoscale ceria administration. An ~5% aqueous dispersion of citrate-stabilized 30 nm ceria, synthesized and characterized in-house, or vehicle, was iv infused into rats terminated 1, 7, 30, or 90 days later. Cageside observations were obtained daily, body weight weekly. Daily urinary and fecal cerium outputs were …

Manganese Distribution Across The Blood-Brain Barrier. Iv. Evidence For Brain Influx Through Store-Operated Calcium Channels, Janelle S. Crossgrove, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

Manganese (Mn) is a required co-factor for many ubiquitous enzymes; however, chronic Mn overexposure can cause manganism, a parkinsonian-like syndrome. Previous studies showed Mn influx into brain is carrier-mediated, though the putative carrier(s) were not established. Studies conducted with cultured bovine brain microvascular endothelial cells (bBMECs), which comprise the blood–brain barrier, revealed ⁵⁴Mn (II) uptake positively correlated with pH, was temperature-dependent, and was sodium- and energy-independent. Brain ⁵⁴Mn uptake correlated inversely with calcium (Ca) concentration, but ⁴⁵Ca uptake was unaltered by high Mn concentration. Lanthanum (La), a non-selective inhibitor of several Ca channel types, as well as …

Manganese Distribution Across The Blood-Brain Barrier. I. Evidence For Carrier-Mediated Influx Of Managanese Citrate As Well As Manganese And Manganese Transferrin, Janelle S. Crossgrove, David D. Allen, Bonny L. Bukaveckas, Susan S. Rhineheimer, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

Manganese (Mn) is an essential element and a neurotoxicant. Regulation of Mn movement across the blood–brain barrier (BBB) contributes to whether the brain Mn concentration is functional or toxic. In plasma, Mn associates with water, small molecular weight ligands and proteins. Mn speciation may influence the kinetics of its movement through the BBB. In the present work, the brain influx rates of ⁵⁴Mn²⁺, ⁵⁴Mn citrate and ⁵⁴Mn transferrin (⁵⁴Mn Tf) were determined using the in situ brain perfusion technique. The influx rates were compared to their predicted diffusion rates, which were determined from …

The Toxicology Of Aluminum In The Brain: A Review, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

Aluminum is environmentally ubiquitous, providing human exposure. Usual human exposure is primarily dietary. The potential for significant Al absorption from the nasal cavity and direct distribution into the brain should be further investigated. Decreased renal function increases human risk of Al-induced accumulation and toxicity. Brain Al entry from blood may involve transferrin-receptor mediated endocytosis and a more rapid process transporting small molecular weight Al species. There appears to be Al efflux from the brain, probably as Al citrate. There is prolonged retention of a fraction of Al that enters the brain, suggesting the potential for accumulation with repeated exposure. Al …

In Vitro Assessment Of The Toxicity Of Cocaine And Its Metabolites In The Human Umbilical Artery, Tessa L. Long

Electronic Theses and Dissertations

An in vitro model was used to assess the effect of cocaine and its metabolites on the umbilical artery. Objectives were to pharmacologically confirm the presence of adrenergic innervation using tyramine, evaluate the ability of cocaine, benzoylecgonine, norcocaine and cocaethylene to potentiate vasoconstriction by serotonin and norepinephrine, examine the ability of ketanserin to block the enhanced vasoconstriction produced by cocaine, and determine displacement of 3 H-ketanserin by serotonin, norepinephrine, tyramine and mianserin. The vasoconstrictive effect of tyramine (100 μM) was enhanced in the presence of cocaine by 257%. Vasoconstrictive effects of serotonin and norepinephrine were significantly enhanced by cocaine by …