Toxicology Commons^™

Examining Mechanism Of Toxicity Of Copper Oxide Nanoparticles To Saccharomyces Cerevisiae And Caenorhabditis Elegans, Michael Joseph Mashock

Dissertations (1934 -)

Copper oxide nanoparticles (CuO NPs) are an up and coming technology increasingly being used in industrial and consumer applications and thus may pose risk to humans and the environment. In the present study, the toxic effects of CuO NPs were studied with two model organisms Saccharomyces cerevisiae and Caenorhabditis elegans. The role of released Cu ions during dissolution of CuO NPs in growth media were studied with freshly suspended, aged NPs, and the released Cu2+ fraction. Exposures to the different Cu treatments showed significant inhibition of S. cerevisiae cellular metabolic activity. Inhibition from the NPs was inversely proportional to size …

Fipronil Promotes Adipogenesis Via Ampkα-Mediated Pathway In 3t3-L1 Adipocytes, Quancai Sun, Jeremy Yang, Kyong-Sup Yoon, John M. Clark, Yeonhwa Park

SIUE Faculty Research, Scholarship, and Creative Activity

Emerging evidence suggests that organochlorine, organophosphorus and neonicotinoid insecticide exposure may be linked to the development of obesity and type 2 diabetes. However, there is no knowledge of the potential influence of fipronil, which belongs to the phenylpyrazole chemical family, on obesity. Thus, the goal of this study was to determine the role of fipronil in adipogenesis using 3T3-L1 adipocytes. Fipronil treatment, at 10 mM, increased fat accumulation in 3T3-L1 adipocytes as well as promoted key regulators of adipocyte differentiation (CCAAT/enhancer-binding protein α and peroxisome proliferator-activated receptor gamma-γ), and key regulators of lipogenesis (acetyl-CoA carboxylase and fatty acid synthase). The …

Anticonvulsant And Procognitive Properties Of Novel Histamine H3 Receptor Antagonists In Male Adult Rats, Ali Kassem Saad

Theses

To determine the potential of histamine H3 receptor (H3R) ligands as new antiepileptic and procognitive drugs, aromatic ether derivatives (1-12) belonging to the nonimidazole class of ligands, with high in-vitro binding affinity at human H3R, were tested for their in-vivo anticonvulsive activity in maximal electroshock (MES)-, pentylenetetrazole (PTZ)-, and strychnine (STR)-induced seizure models in male adult rats having phenytoin (PHT) and valproic acid (VPA) as the reference antiepileptic drugs, pitolisant (PIT) as the standard H3R antagonist/inverse agonist, and donepezil (DOZ) as a reference procognitive drug. Among the H3R ligands (1-12) tested in the current project, H3R …

Expansion Of The Knockdown Resistance Frequency Map For Human Head Lice (Phthiraptera: Pediculidae) In The United States Using Quantitative Sequencing, K J. Gellatly, S Krim, D J. Palenchar, K Shepherd, Kyong-Sup Yoon, C J. Rhodes, S H. Lee, J M. Clark

SIUE Faculty Research, Scholarship, and Creative Activity

Pediculosis is a prevalent parasitic infestation of humans, which is increasing due, in part, to the selection of lice resistant to either the pyrethrins or pyrethroid insecticides by the knockdown resistance (kdr) mechanism. To determine the extent and magnitude of the kdr-type mutations responsible for this resistance, lice were collected from 138 collection sites in 48 U.S. states from 22 July 2013 to 11 May 2015 and analyzed by quantitative sequencing. Previously published data were used for comparisons of the changes in the frequency of the kdr-type mutations over time. Mean percent resistance allele frequency (mean % RAF) values across …

Assessment Of The Role Of Poly (Adp-Ribose) Polymerase In Drug-Induced Cardiomyopathy, Alexis I. Brinkerhoff

USF Tampa Graduate Theses and Dissertations

Drug-induced cardiotoxicity has resulted in a thorough evaluation of patient doses, treatments, and rehabilitation. One of the most commonly prescribed chemotherapeutic agents is cyclophosphamide. The active metabolite, acrolein, is one of the most potent inducers of cardiomyopathy. In this study, research was conducted on the H9c2 (2-1) cardiomyocyte cell line derived from the embryonic myocardium of rattus norvegicus to assess its competency for evaluation of the change in poly (ADP-ribose) polymerase (PARP) activity. The application of this model to study the effects of acrolein on PARP activation was chosen as an ideal determinant of cell damage produced by nitrogen mustards. …

Assessment Of Acrolein-Induced Toxicity Using In-Vitro Modeling To Evaluate The Role Of Parp Inhibitors In Reducing Cytotoxicity, Kristina Marie Harand

USF Tampa Graduate Theses and Dissertations

Acrolein is an electrophilic α, β-unsaturated aldehyde. Additionally, acrolein is a metabolite of the antineoplastic alkylating agent cyclophosphamide and is implicated in off-target effects, including to bladder hemorrhagic cystitis and cyclophosphamide-induced cardiotoxicity, both of which have led to serious secondary iatrogenic injury during and following chemotherapy. At low concentrations acrolein inhibits cell proliferation without inducing apoptosis, while at high concentrations may result in secondary apoptosis promotion. This investigation assessed the role of the enzyme poly (ADP-ribose) polymerase (PARP) in acrolein induced toxicity using the established toxicological H9c2 (2-1) cardiomyoblast in vitro model. H9c2 (2-1) cells were plated in 24-well plates …

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 …

Extracorporeal Membrane Oxygenation (Ecmo) For Severe Toxicological Exposures: Review Of The Toxicology Investigators Consortium (Toxic)., G S. Wang, R Levitan, T J. Wiegand, Jennifer Lowry, R F. Schult, S Yin, Toxicology Investigators Consortium

Manuscripts, Articles, Book Chapters and Other Papers

Although there have been many developments related to specific strategies for treating patients after poisoning exposures, the mainstay of therapy remains symptomatic and supportive care. One of the most aggressive supportive modalities is extracorporeal membrane oxygenation (ECMO). Our goal was to describe the use of ECMO for toxicological exposures reported to the American College of Medical Toxicology (ACMT) Toxicology Investigators Consortium (ToxIC). We performed a retrospective review of the ACMT ToxIC Registry from January 1, 2010 to December 31, 2013. Inclusion criteria included patients aged 0 to 89 years, evaluated between January 2010 through December 2013, and received ECMO for …

Role Of The Calcium Plateau In The Neuronal Injury And Behavioral Morbidities Following Organophosphate Intoxication, Laxmikant S. Deshpande, Robert E. Blair, Kristin F. Phillips, Robert J. Delorenzo

Neurology Publications

Organophosphate (OP) chemicals include nerve agents and pesticides, and there is a growing concern of OP based chemical attacks against civilians. Current antidotes are essential in limiting immediate mortality associated with OP exposure. However, further research is needed to identify molecular mechanisms underlying long-term neurological deficits following survival of OP toxicity in order to develop effective therapeutics. We have developed rat survival models of OP induced status epilepticus (SE) that mimic chronic mortality and morbidity following OP intoxication. We have observed significant elevations in hippocampal calcium levels after OP SE that persisted for weeks following initial survival. Drugs inhibiting intracellular …

3,5-Dichloroaniline: Biotransformation And Mechanistic Aspects Of Nephrotoxicity In Vitro, Christopher Robert Racine

Theses, Dissertations and Capstones

Chlorinated anilines have been used as important chemical intermediates in the production of a wide variety of pharmaceutical, industrial, and agricultural products. Exposure to chloroanilines can arise in both occupational and environmental settings and can lead to toxicity to multiple organs, including the kidney. Previous studies have established that of the mono- and dichlorinated anilines, 3,5-dichloroaniline (3,5-DCA) possesses the most nephrotoxic potential both in vitro and in vivo. However, little is known concerning the role of renal metabolism in nephrotoxicity. The studies presented in the following dissertation are the first to explore the toxicity, metabolism, and bioactivation of 3,5-DCA in …

An Analysis Of Virtual Place Learning/Navigation In Children And Young Adults Prenatally Exposed To Alcohol, Neil Christopher Dodge

Wayne State University Dissertations

Fetal alcohol spectrum disorder refers to the spectrum of disorders resulting from prenatal alcohol exposure and is the leading cause of preventable mental retardation. Rodent studies have found that prenatal alcohol exposure impairs performance on the Morris water maze. This task requires the rodent to use distal room cues to locate a hidden platform in a pool of opaque water. Successful performance on this task is dependent upon hippocampal function. Rodents prenatally exposed to alcohol are impaired on the Morris water maze and show damage to hippocampal neurons. A human analogue of the Morris water maze, the virtual water maze …

An Ecotoxicological Survey Of Tributaries Of The Selenge River, Mongolia, August 2010, Viktor T. Komov, Ch. Javzan, William G. Brumbaugh

Erforschung biologischer Ressourcen der Mongolei / Exploration into the Biological Resources of Mongolia, ISSN 0440-1298

The biodiversity of the Selenga river basin and the receiving waters of the lake Baikal, are among the greatest in the world with over 1,700 known endemic species of plants and animals. Mining activities along the Selenga river and its tributaries pose a major threat of chemical contamination, potentially reducing habitat quality and suitability for aquatic species. Moreover, the Selenga river serves as a major water source for the lake Baikal. Little information exists on the chemical contaminant concentrations in the Selenga river basin. Thus, the objectives of our study were to evaluate the concentrations of metals in soil, sediment, …

Farnesol-Mediated Regulation Of Hepatic Lipid Metabolism In Heparg Cells, Asmita Pant

Wayne State University Dissertations

Non-alcoholic fatty liver disease is emerging as one of the most common liver disorders worldwide and is characterized by accumulation of triglycerides (TGs) in liver. The endogenous isoprenoid farnesol reduces hepatic TG levels in rodents, and this effect appears to involve at least two nuclear receptors, peroxisome proliferator-activated receptor α and farnesoid X receptor (FXR). However, farnesol’s effects on human hepatic lipid metabolism are currently unknown. The objective of this study is to evaluate how farnesol treatment would affect hepatic lipid accumulation and metabolism in a cellular model of human hepatic steatosis that was created by incubating the hepatocyte-like HepaRG …

Bioactivity/Cytotoxicity Of Micro-/Nano-Materials And Novel Development Of Fiber-Optic Probes For Single Cell Monitoring, Qingbo Yang

Doctoral Dissertations

"Manufactured nano-/micro-materials (MNMs) have been widely used and their interactions with niche biological environment are highly concerned for both of their biohazardous and bioactive effects, whereas no available comprehensive evaluations or regulations have been provided yet. This dissertation thus focuses on three major aspects: 1) fundamental toxicity understandings of a typical MNMs (zinc oxide nanoparticles), 2) bioactivity evaluations of representative bioactive MNMs, and 3) development of novel micro-probes for high spatial resolution monitoring. Firstly, the NP's concentration, irradiation, hydrodynamic size, and the localized pH, ionic strength, NP zeta-potential as well as dissolved oxygen levels were found correlated with the production …

Consequences Of Developmental Lead (Pb2+) Exposure On Reproductive Strategies In Drosophila, Elizabeth Kathleen Peterson

Legacy Theses & Dissertations (2009 - 2024)

Anthropogenic lead (Pb) pollution is ubiquitous in the environment and a risk factor for both human and wildlife health. Pb exposure has the potential to alter reproductive strategies with respect to mate choice and reproductive output. This could be especially deleterious if these changes disrupt adaptive behavioral and reproductive life history strategies. Therefore, the overall aim of this body of work was to examine the consequences of developmental Pb exposure on reproductive strategies, using Drosophila melanogaster as a model system. In all experiments, D. melanogaster were reared from egg stage to adulthood in either control or leaded medium and were …

Development Of A Dreissena Bioassay To Assess The Toxicity Of Contaminants Across Two Life-History Stages, Caroline Joyce Addis

Wayne State University Theses

Dreissenid mussels (Dreissena polymorpha and D. bugensis) have rapidly become widespread and ubiquitous in North America since their introduction into the Great Lakes in the 1980s. The resulting environmental and economic impacts of their invasion have been extensive, negatively affecting biodiversity and costing millions of dollars in control efforts and damage to power generation and water treatment facilities. Although dreissenids are often associated with negative impacts, they may present a practical tool for toxicology studies. The typically sessile behavior of the benthic adults coupled with the planktonic nature of the veligers allow for a more complete evaluation of water quality …

The Influence Of Abiotic Factors On The Uptake And Elimination Of 3-Trifluoromethyl-4-Nitrophenol By Larval Sea Lamprey (Petromyzon Marinus), Benjamin Livingston Hlina

Theses and Dissertations (Comprehensive)

The backbone of sea lamprey (Petromyzon marinus) control in the Great Lakes is the use of the piscicide, 3-trifluoromethyl-4-nitrophenol (TFM), which is applied to streams containing larval sea lampreys. However, TFM effectiveness can be influenced by abiotic factors such as pH and temperature, which fluctuate daily and seasonally. The objectives of this thesis were to evaluate the influence of pH, temperature, and season on the toxicity, uptake, and elimination of TFM by larval sea lamprey. Radio-labeled TFM (¹⁴C-TFM) was used to determine how TFM uptake rates varied at different water pHs or temperatures during exposure to …

The Role Of Oxidative Stress In The Mechanisms Of Ammonia-Induced Brain Swelling And Tolerance In The Goldfish (Carassius Auratus), David F. Jones Lisser Mr.

Theses and Dissertations (Comprehensive)

Toxic build-ups of ammonia can cause potentially fatal brain swelling in mammals, but such swelling is reversible in the anoxia- and ammonia-tolerant goldfish (Carassius auratus). The mechanisms of ammonia-induced brain swelling and tolerance remain elusive, but several studies have suggested a role for reactive oxygen species (ROS), which may damage proteins and lipids in the plasma membrane of astrocytes in the brain. As a result, osmotic gradients across cell membranes may be altered leading to water uptake by astrocytes and swelling. While a role for ROS has been proposed in mammals, no studies have addressed this question in …

Nickel And Copper Mixture Toxicity To Daphnia In Soft Water, Prachi Deshpande

Theses and Dissertations (Comprehensive)

Industrially important metals, such as Cu and Ni, sometimes are present at elevated concentrations in lakes, including those in the Sudbury, ON region. Although they are essential metals, their divalent-cation state (Cu²⁺ and Ni²⁺) can be toxic at high concentrations in the water. The free-ion toxicity of each of these metals has been studied in isolation, but rarely as a mixture. The economic importance of Cu²⁺ and Ni²⁺ makes them essential to study in the context of mixture toxicity. The objectives were to: (1) determine Cu and Ni mixture toxicity to Daphnia through acute LC50 …

Do Toxicity Modifying Factors Influence Acute Or Chronic Toxicity Of Thulium To Hyalella Azteca?, Alexandria H. Loveridge

Theses and Dissertations (Comprehensive)

The industrial demand for rare earth elements (REEs) is growing and as a result, environmental exposure is a concern. Very little is understood about the toxicity of REEs in aquatic environments. The objective of this research is to evaluate the acute and chronic toxicity of Tm and to also understand the toxicity modifying influence of dissolved organic matter (DOM) and cationic competition (Ca2+, Mg2+ and Na+). Furthermore, the aim of this study was to determine linkages between Tm bioaccumulation, growth and survival during chronic exposures. Standard methods (Environment Canada) were followed for both 96h acute and 14d chronic tests, in …

The Role Of Renal Replacement Therapy In The Management Of Pharmacologic Poisonings, Aibek E. Mirrakhimov, Aram Barbaryan, Adam Gray, Taha Ayach

Internal Medicine Faculty Publications

Pharmacologic toxicities are common and range from mild to life-threatening. The aim of this study is to review and update the data on the role of renal replacement therapy (RRT) in the management of various pharmacologic poisonings. We aim to provide a focused review on the role of RRT in the management of pharmacological toxicities. Relevant publications were searched in MEDLINE with the following search terms alone or in combination: pharmacologic toxicity, hemodialysis, hemofiltration, renal replacement therapy, toxicology, poisonings, critical illness, and intensive care. The studies showed that a pharmacologic substance should meet several prerequisites to be deemed dialyzable. These …

Heavy Metal Accumulation In Urban Soil: A Phytoextraction Method Review, Diane M. Nelson

Dissertations, Master's Theses and Master's Reports

Lead (Pb), cadmium (Cd), and arsenic (As) are three common non-essential heavy metals found in urban soils and can prove toxic to animals, humans, and some plants at low concentrations. The main exposure pathways of heavy metals in humans are through ingestion and inhalation of soil particles and ingestion of contaminated food. When dealing with contaminated soil in urban environments, activities like urban gardening can increase the likelihood of these exposure pathways, so heavy metal toxicity from contaminated soil can become a greater risk with the increased interest in urban agriculture. The US EPA created target concentrations for these heavy …

Validation Of Type 2 Diabetes Risk Variants Identified By Genome-Wide Association Studies In Northern Han Chinese, Ping Rao, Yong Zhou, Siqi Ge, Anxin Wang, Xinwei Yu, Mohamed Ali Alzain, Andrea K. Veronica, Jing Qiu, Manshu Song, Jie Zhang, Hao Wang, Honghong Fang, Qing Gao, Youxin Wang, Wei Wang

Research outputs 2014 to 2021

Background:

More than 60 genetic susceptibility loci associated with type 2 diabetes mellitus (T2DM) have been established in populations of Asian and European ancestry. Given ethnic differences and environmental factors, validation of the effects of genetic risk variants with reported associations identified by Genome-Wide Association Studies (GWASs) is essential. The study aims at evaluating the associations of T2DM with 29 single nucleotide polymorphisms (SNPs) from 19 candidate genes derived from GWASs in a northern Han Chinese population.

Method:

In this case-control study, 461 T2DM-diagnosed patients and 434 controls were recruited at the Jidong oil field hospital (Hebei, China) from January …

Exploration Of The Srx-Prx Axis As A Small-Molecule Target, Murli Mishra

Theses and Dissertations--Toxicology and Cancer Biology

Lung cancer is a leading cause of cancer-related mortality irrespective of gender. The Sulfiredoxin (Srx) and Peroxiredoxin (Prx) are a group of thiol-based antioxidant proteins that plays an essential role in non-small cell lung cancer. Understanding the molecular characteristics of the Srx-Prx interaction may help design the strategies for future development of therapeutic tools. Based on existing literature and preliminary data from our lab, we hypothesized that the Srx plays a critical role in lung carcinogenesis and targeting the Srx-Prx axis or Srx alone may facilitate future development of targeted therapeutics for prevention and treatment of lung cancer. First, …

Toxicity Of Engineered Nanomaterials To Plant Growth Promoting Rhizobacteria, Ricky W. Lewis

Theses and Dissertations--Plant and Soil Sciences

Engineered nanomaterials (ENMs) have become ubiquitous in consumer products and industrial applications, and consequently the environment. Much of the environmentally released ENMs are expected to enter terrestrial ecosystems via land application of nano-enriched biosolids to agricultural fields. Among the organisms most likely to encounter nano-enriched biosolids are the key soil bacteria known as plant growth promoting rhizobacteria (PGPR). I reviewed what is known concerning the toxicological effects of ENMs to PGPR and observed the need for high-throughput methods to evaluate lethal and sublethal toxic responses of aerobic microbes. I addressed this issue by developing high-throughput microplate assays which allowed me …

The Effects Of Manufactured Nanomaterial Transformations On Bioavailability, Toxicity And Transcriptomic Responses Of Caenorhabditis Elegans, Daniel L. Starnes

Theses and Dissertations--Plant and Soil Sciences

In recent decades, there has been a rapid expansion in the use of manufactured nanoparticles (MNPs). Experimental evidence and material flow models predict that MNPs enter wastewater treatment plants and partition to sewage sludge and majority of that sludge is land applied as biosolids. During wastewater treatment and after land application, MNPs undergo biogeochemical transformations (aging). The primary transformation process for silver MNPs (Ag-MNPs) is sulfidation, while zinc oxide MNPs (ZnO-MNPs) most likely undergo phosphatation and sulfidation. Our overall goal was to assess bioavailability and toxicogenomic impacts of both pristine, defined as-synthesized, and aged Ag- and ZnO-MNPs, as well as …

From Seed To Sky: Impacts Of Explosive Compounds On Vegetation Across Spatial And Developmental Scales, Stephen M. Via

Theses and Dissertations

Explosive compounds are broadly distributed across the globe as a result of nearly two centuries of munitions use in warfare and military activities. Two explosive compounds have seen disproportionate use; RDX (hexahydro-1,3,5-trinitro-1,3,5-triazine) and TNT (2-methyl- 1,3,5-trinitrobenzene), being the most commonly found explosives in the environment. The effects of explosives on biota have been studied in great detail; however, there is a general lack of understanding with regard to broader ecological impacts of these contaminants. My dissertation objective was to follow the impacts of explosive compounds on vegetation across scales. Impacts on vegetation at the species scale alter community composition via …

Identification Of Methylene Diphenyl Diisocyanate Thermal Degradation Products In A Generation Chamber By Liquid Chromatography Coupled With Tandem Mass Spectrometry, Sébastien Gagné, Yves Cloutier

Études primaires

Isocyanate thermal degradation characterization by liquid chromatography coupled with electrospray tandem mass spectrometry has been performed to elucidate the methylene diphenyl diisocyanate (MDI) thermal degradation structure emitted in a generation chamber using a temperature between 50°C and 180°C to produce MDI vapors. [M+H]⁺ ions containing an isocyanate functional group were studied by tandem mass spectrometry. The [M+H]⁺ ion analyses based on the combination of full scans and precursor ion scans were useful for identifying all structures. The compounds emitted were identified and validated as a mixture of compounds containing amine and isocyanate functions. Residual MDI, methylene diphenyl amino-isocyanate, …

Implementation And Evaluation Of An Analytical Method For A Novel Derivatizing Agent To Measure 4,4'-Methylene Diphenyl Diisocyanate Atmospheres, Silvia Puscasu, Simon Aubin, Mark Spence, Sébastien Gagné

Études primaires

Accurate measurement of 4,4'-methylene diphenyl diisocyanate (MDI) atmospheres is a challenge since the molecule is both chemically reactive and likely to be present in aerosol form when heated and sprayed because of its low vapor pressure. Meeting this challenge requires optimizing both the sampling device used and the derivatization agent employed to stabilize the isocyanate functional group. This study describes the use of a novel derivatization reagent for isocyanate sampling to address the challenge of MDI aerosol exposure sampling. Like most conventional derivatizing agents for isocyanates, 1,8-diaminonapthalene (DAN) reacts with isocyanate functional groups to form a urea. However, unlike other …

The Sublethal Physiological Effects Of Exposure To Copper And Silver Mixtures On Rainbow Trout (Oncorhynchus Mykiss), Wesley Truong

Theses and Dissertations (Comprehensive)

The mechanisms behind metal-metal interactions in freshwater environments are currently not well understood. Freshwater environments consist of many different types of metals, from those naturally present such as copper (Cu) and those that originate from anthropogenic sources like silver (Ag). Both Cu and Ag use apical sodium (Na⁺) channels for uptake into the gills of freshwater fish. In the gills, the mechanisms of Cu²⁺ and Ag⁺ toxicity appear to be similar to one another, which is by inhibiting Na⁺ /potassium (K⁺)- adenosine triphosphatase (NKA) and carbonic anhydrase (CA). Inhibition of NKA and CA …