Toxicology Commons^™

Emerging Chromatin Regulators In Response To Heavy Metal Exposure, Wesley Saintilnord

Theses and Dissertations--Molecular and Cellular Biochemistry

Environmental exposure to heavy metals poses significant threats to human health as they are associated with various developmental and chronic pathologies such as reproductive defects and cancers. Despite their profound risks, a comprehensive understanding of their disease-causing mechanisms is lacking. Most studies point to reactive oxygen species-induced DNA damage; however, their mutagenic potential is relatively weak suggesting the involvement of alternative mechanisms. One important, yet underexplored mechanism, is their ability to rewire the epigenome via DNA methylation and histone variant incorporation, leading to aberrant gene regulatory networks.

This study investigates the epigenetic mechanisms targeted by two ubiquitous heavy metals with …

Enhancing Translation: A Need To Leverage Complex Preclinical Models Of Addictive Drugs To Accelerate Substance Use Treatment Options, Christa Corley, Ashley Craig, Safiyah M. Sadek, Julie A. Marusich, Samar N. Chehimi, Ashley M. White, Lexi J. Holdiness, Benjamin C. Reiner, Cassandra D. Gipson

Markey Cancer Center Faculty Publications

Preclinical models of addictive drugs have been developed for decades to model aspects of the clinical experience in substance use disorders (SUDs). These include passive exposure as well as volitional intake models across addictive drugs and have been utilized to also measure withdrawal symptomatology and potential neuro- behavioral mechanisms underlying relapse to drug seeking or taking. There are a number of Food and Drug Administration (FDA)-approved medications for SUDs, however, many demonstrate low clinical efficacy as well as potential sex differences, and we also note gaps in the continuum of care for certain aspects of clinical ex- periences in individuals …

Perfluorooctanesulfonic Acid Exposure Leads To Downregulation Of 3-Hydroxy-3-Methylglutaryl-Coa Synthase 2 Expression And Upregulation Of Markers Associated With Intestinal Carcinogenesis In Mouse Intestinal Tissues, Josiane Weber Tessmann, Pan Deng, Jerika Durham, Chang Li, Moumita Banerjee, Qingding Wang, Ryan A. Goettl, Daheng He, Chi Wang, Eun Y. Lee, B. Mark Evers, Bernhard Hennig, Yekaterina Y. Zaytseva

Markey Cancer Center Faculty Publications

Perfluorooctanesulfonic acid (PFOS) is a widely recognized environment pollutant known for its high bio- accumulation potential and a long elimination half-life. Several studies have shown that PFOS can alter multiple biological pathways and negatively affect human health. Considering the direct exposure to the gastrointestinal (GI) tract to environmental pollutants, PFOS can potentially disrupt intestinal homeostasis. However, there is limited knowledge about the effect of PFOS exposure on normal intestinal tissues, and its contribution to GI- associated diseases remains to be determined. In this study, we examined the effect of PFOS exposure on the gene expression profile of intestinal tissues of …

Evaluating The Risk Posed By Gadolinium In The Grand River Watershed, Johann Memmel

Theses and Dissertations (Comprehensive)

Gadolinium (Gd) is a rare earth element (REE), primarily used in contrast agents for magnetic resonance imaging (MRI), with additional applications in metallurgy, phosphors, neutron shielding, and other niche applications. Both Gd and Gd-based contrast agents (GBCAs, the form used for MRIs) have been detected downstream of wastewater effluent discharges and there is currently little research into the risk this poses to aquatic ecosystems. This study investigated the potential environmental risks of Gd and GBCAs using the Grand River watershed (GRW) in southwestern Ontario as a model ecosystem due to it containing a variety of land uses (urban, industrial, agricultural) …

Investigating The Impact Of Chronic Inflammatory Pain On Ethanol Consumption In Mouse Models., Joshua L. Hunt

Theses and Dissertations

Chronic pain affects nearly 20% of Americans annually and for many alcohol provides a convenient and legally acquired palliative. Population-based studies have suggested a link between increased alcohol use and reduced pain, but chronic or excessive alcohol use potentiates the risk to develop alcohol dependence and neuropathy. However, sex differences in chronic pain and alcohol abuse are still not well understood. In the present study, we investigated whether chronic inflammatory pain using the inflammatory agent Complete Freund’s Adjuvant (CFA) model could alter ethanol consumption in male and female C57BL/6J mice. We observed that only CFA-treated male mice increased their ethanol …

Exploring Serotonin 1b Autoreceptor Mediated Regulation Of Serotonin Transporter In Female Mice, Sanyukta Jalihalkar

Theses and Dissertations

Rationale: Serotonin (5-HT) is a crucial neurotransmitter involved in regulating various physiological processes. Dysregulation of the serotonergic system has been implicated in several neuropsychiatric disorders. Though numerous 5-HT receptors exist, the 5-HT transporter (SERT) is responsible for 5-HT clearance in the brain and periphery. 5-HT_1Bautoreceptors regulate 5-HT release and interact with glycogen synthase kinase-3β (GSK3β), which can modulate SERT function via specific Ser44/48 phosphorylation sites. While these findings suggest a potential interplay between 5-HT_1Band GSK3β-mediated SERT phosphorylation in regulating extracellular 5-HT, the primary causal molecular link remains unknown.

Objectives: To investigate if 5-HT_1B activation by …

Neurodevelopmental Vulnerability To Gestational Ozone Exposure, Vishnupriya Alavala, Sarah E. Brent, Christopher G. Canal, Joseph Wang, Russell P. Hunter, Matthew J. Campen, Andrew K. Ottens

UROP Posters

Ambient air pollution accounts for about 4.2 million premature deaths annually per the World Health Organization. Ozone (O3) is a highly reactive air pollutant found in smog and is implicated in cellular damage leading to organ dysfunction. Ambient air pollution is associated with neurodevelopmental, behavioral, and cognitive disorders though ozone’s role is unknown. Studies here look at ozone exposure shortly after implantation vs. shortly before term to evaluate differences in neurodevelopmental susceptibility over time.

To inquire on the effects of ozone on the fetal brain, pregnant Sprague-Dawley rats were exposed once to 0.3 ppm of O3 or filtered air (FA) …

Geochemistry Of Rare Earth Elements In Simulated Natural Waters: Experiments And Modelling Of Precipitation, Complexation, And Bioavailability., Samantha Zulian

Theses and Dissertations (Comprehensive)

Rare earth elements (REEs) are an important part of modern technology and used for many applications. Mining, agriculture, improper recycling and medical applications can increase the concentration of these elements in surface waters. Metals in the environment including REEs can be found naturally but understanding the implications increase concentrations from anthropogenic inputs is important. REE mobility, persistence and toxicity is imperative to risk assessment as Canada begins to mine REE. Ultimately, as with other metals, the impacts of REEs in the environment should be dependent on the specific physical and chemical forms of the elements. Fractionation provides a practical method …

Assessing Stormwater Management Pond Water Quality, Function, And The Potential Biotic Effects To Receiving Waters, Mitchell Elstone

Theses and Dissertations (Comprehensive)

The use of stormwater management ponds (SWMPs) has been increasing over the past five decades. However, an in-depth understanding of the daily performance of SWMPs and functionality during cold periods is limited. This is in part because mandated monitoring is relatively infrequent, and the assumption that SWMPs are inactive between storm events and during the winter. The goals of this research were to better understand daily stormwater (SW) characteristics, the performance of SWMPs based on current forms of evaluation and assess the potential for SWMP effluent to impact downstream biota. Influent and effluent samples from two SWMPs were collected daily …

A Review Of Rattlesnake Venoms, Phuc Phan, Anant Deshwal, Tyler Anthony Mcmahon, Matthew Slikas, Elodie Andrews, Brian Becker, Thallapuranam Krishnaswamy Suresh Kumar

Chemistry & Biochemistry Faculty Publications and Presentations

Venom components are invaluable in biomedical research owing to their specificity and potency. Many of these components exist in two genera of rattlesnakes, Crotalus and Sistrurus, with high toxicity and proteolytic activity variation. This review focuses on venom components within rattlesnakes, and offers a comparison and itemized list of factors dictating venom composition, as well as presenting their known characteristics, activities, and significant applications in biosciences. There are 64 families and subfamilies of proteins present in Crotalus and Sistrurus venom. Snake venom serine proteases (SVSP), snake venom metalloproteases (SVMP), and phospholipases A2 (PLA2) are the standard components in Crotalus …

Aversion Properties Of Retrorsine, Retrorsine Nitrogen Oxide And Frosted Senecio Latifolius, Leendert D. Snyman

Poisonous Plant Research (PPR)

Two pilot trials, investigating the aversive properties of retrorsine and retrorsine nitrogen oxide and that of frosted Senecio latifolius, were executed. Retrorsine and retrorsine-NO (the toxic principles of Senecio retrorsus), unlke sceleratine-NO (the toxic principle of another hepatotoxic pyrrolizidine alkaloid containing plant, namely S. latifolius), were not capable of establishing aversion when given to a sheep. Frosted S. latifolius given to a sheep also did not induce aversion. However, a sheep averted to S. latifolius (non-frosted) refused eating frosted S. latifolius.

Sceleratin Nitrogen Oxide As Aversive Agent In Conditioning Livestock To Avoid Senecio Latifolius, Leendert D. Snyman

Poisonous Plant Research (PPR)

Sceleratine nitrogen oxide, when administered together with a dichloromethane extract of Senecio latifolius, successfully conditioned cattle and sheep to avoid milled freeze dried S. latifolius mixed with maize meal. This treatment was effectively applied in conditioning steers to refuse eating S. latifolius grown in pots.

Corrigendum To "Ssr-Based Molecular Diagnosis For Taiwan Tea Cultivars And Its Application In Identifying Cultivar Composition Of The Processed Tea"

Journal of Food and Drug Analysis

No abstract provided.

Acknowledgment Of Reviewers

Journal of Food and Drug Analysis

No abstract provided.

Application Of The Us Food And Drug Administration’S Sentinel Routine Querying Tools To The Taiwan Sentinel Data Model-Formatted National Health Insurance Research Database, Fang-Ju Lin, Ling-Ya Huang, Chi-Chuan Wang, Sengwee Toh

Journal of Food and Drug Analysis

The U.S. Food and Drug Administration’s Sentinel System is a leading distributed data network for drug safety surveillance in the world. The National Health Insurance Research Database (NHIRD) in Taiwan was converted into the Taiwan Sentinel Data Model (TSDM) based on the Sentinel Common Data Model (SCDM) version 6.0.2. The goal of this study was to investigate the feasibility of applying the same study designs, analytic choices, and analytic tools as used by the U.S. Sentinel System to examine the same drug-outcome associations in the TSDM-formatted NHIRD. Four known drug-outcome associations previously examined by the U.S. Sentinel System were selected …

Isolation Of Glp-1 Enhancing Indolizidine Alkaloids From Boehmeria Formosana, Ching-Yi Lu, Zheng-Ying Huang, Meng-Chin Chen, Hui-Kang Liu, Shoei-Sheng Lee, Chia-Chuan Chang

Journal of Food and Drug Analysis

Boehmeria formosana, with its related species, demonstrates anti-glycemic effect, inhibition of HBV production, anti-cancer activities, etc. Some indolizidine alkaloids from the same genus are bioactive but sensitive to light. To overcome this problem and obtain more phenanthroindolizidine alkaloids, isolation was performed in darkness, yielding 10 new indolizidine alkaloids and 17 known compounds. Among them, seven enhanced glucagon-like receptor 1 (GLP-1) activity at 50 mM, especially 14 and 6 (3.5- and 2.3-fold than the negative control). This procedure yielded bioactive indolizidine alkaloids with novel structures.

An Integrated Strategy To Evaluate Active Substances Of Astragali Radix-Carthami Flos Combination On The Treatment Of Cerebral Ischemia Reperfusion Injury Based On Tqsm Polypharmacokinetics And Pharmacodynamics, Qiang Zeng, Chang Li, Shouchao Xu, Yu He

Journal of Food and Drug Analysis

As a classic herb pair, Astragali Radix-Carthami Flos (AR-CF) has revealed good biological activity in the treatment of cerebral ischemia/reperfusion injury (CI/RI), which remained to be further clarified together with the underlying efficacy related compounds for material basis. In this study, the nine formulations were obtained by L₉(3⁴) orthogonal array design of four active fractions (saponin and flavonoid extracted from AR, safflower yellow and safflower red extracted from CF). The concentrations of eleven components and the levels of four biochemical indicators in rat plasma were continuously detected after intragastric administration of nine formulations, respectively. The collected …

Cryptocaryone Induces Apoptosis In Human Hepatocellular Carcinoma Cells By Inhibiting Aerobic Glycolysis Through Akt And C-Src Signaling Pathways, Chen-Lin Yu, Yu-Wei Lai, Jih-Jung Chen, Jie-Jen Lee, Tsung-Hsien Chou, Chen-Chen Huang, Shih-Chia Liu, Guang-Wei Chen, Chung‐Hsin Tsai, Shih-Wei Wang

Journal of Food and Drug Analysis

Hepatocellular carcinoma (HCC) is the most common form of liver cancer, with the second highest mortality rate in all cancer. Energy reprogramming is one of the hallmarks of cancer, and emerging evidence showed that targeting glycolysis is a promising strategy for HCC treatment. Cryptocaryone has been shown to display promising anti-cancer activity against numerous types of cancer. Previous study also indicated that cryptocaryone induces cytotoxicity by inhibiting glucose transport in cancer cells, but the detailed mechanism still needs to be elucidated. Therefore, this study aimed to investigate the relationship between the anti-cancer effect and glycolytic metabolism of cryptocaryone in human …

Dehulled Adlay (Coix Lachryma-Jobi L.) Ameliorates Hepatic Gluconeogenesis And Steatosis In Streptozotocin/High-Fat Diet-Induced Diabetic Rats, Shing-Hwa Liu, Wan-Hsin Wu, Huei-Ping Tzeng, Wenchang Chiang, Meng-Tsan Chiang

Journal of Food and Drug Analysis

Adlay (Coix lachryma-jobi L.) is a traditional Chinese herbal medicine with various biological activities. We investigated the anti-diabetic effects of different parts of adlay seeds, including polished adlay (PA), adlay bran (AB) and dehulled adlay (DA) in a streptozotocin (STZ)/high fat diet (HFD) diabetic rat model (DM). DM rats supplemented with or without PA (43%), AB (3%), or DA (46%) diet for 8 weeks. The plasma glucose and insulin levels and the insulin resistance index (HOMA-IR) were increased in DM group; among the three adlay diets, DA has the best effects attenuating all of these alterations in DM …

Biological And Clinical Significance Of The Age-Rage Axis In The Aggressiveness And Prognosis Of Prostate Cancer, Shih-Hong Khoo, Pei-Ru Wu, Kun-Tu Yeh, Shih-Lan Hsu, Chi-Hao Wu

Journal of Food and Drug Analysis

Dietary factors and chronic hyperglycemia are linked to the formation of advanced glycation end products (AGEs) and prostate cancer (PCa) risk. The activation of the receptor for AGEs (RAGE) acts as a bridge between various RAGE ligands and certain malignancies. This study showed that the interaction of AGEs and RAGE promoted PCa cell proliferation, invasion, and autophagy-mediated survival in response to chemotherapeutic agents. RAGE-overexpressed PCa cells underwent epithelial-mesenchymal transition and showed increased cancer stem cell-like properties. In mouse xenograft models, RAGE-overexpressed cells showed more substantial tumorigenic capacity than parental cells, whereas RAGE knockdown decreased tumorigenicity. The clinical data validated a …