Pharmacology, Toxicology and Environmental Health Commons^™

Mechanisms Of Particulate Hexavalent Chromium-Induced Inhibition Of Homologous Recombination Repair: Targeting The Bcdx2 Complex Considered Through A One Health Perspective., Aggie W. Brownell

Electronic Theses and Dissertations

Lung cancer remains the leading cause of cancer death, often linked to smoking. However, smoking alone does not account for all cases. Exposure to environmental metals like hexavalent chromium [Cr(VI)] also contributes to lung cancer. Cr(VI) causes lung cancer by inducing chromosome instability (CIN), an early hallmark of its carcinogenic mechanism. While it has been established that Cr(VI) induces chromosome instability, the precise mechanisms underlying the chromosome instability are poorly understood. This dissertation investigates the mechanisms of carcinogenesis associated with zinc chromate, a particularly potent particulate form of hexavalent chromium. Studies show Cr(VI) induces DNA double-strand breaks and impairs the …

The Effects Of Pfos Exposure On Zebrafish Dopaminergic Neurodevelopment, Allison G. Fletcher

Departmental Honors & Graduate Capstone Projects

Per- and polyfluoroalkyl substances (PFAS) are a group of environmental contaminants that cause disruptions to the nervous and endocrine systems. Perfluorooctanesulfonate (PFOS) is considered one of the most disruptive PFAS to the nervous system, and may disrupt neurodevelopment of the dopaminergic system, which has been linked to neurodevelopmental disorders like Attention Deficit/Hyperactivity Disorder (ADHD) in humans. I hypothesized that early life PFOS exposure disrupts the development of the dopaminergic system. To test this hypothesis, I exposed zebrafish to 0.05, 0.5, and 5.0 mg/L PFOS through 5 days of embryonic and larval development. To assess acute effects of PFOS on the …

Translation Of The Carcinogenic Dna Breakage-Repair Inhibition Mechanism For Hexavalent Chromium To Its Key Targets: Lung Epithelial Cells, Lung Tissue And Impacts On The Genome., Idoia Meaza Isusi

Electronic Theses and Dissertations

Lung cancer is the leading cause of cancer death worldwide. Hexavalent chromium [Cr(VI)] is a human lung carcinogen with widespread occupational and environmental exposure. Despite the known health risks, how Cr(VI) causes lung cancer remains unclear. This dissertation investigates the mechanisms of Cr(VI)-induced carcinogenesis. Cr(VI) causes DNA damage, specifically DNA double strand breaks, and inhibits homologous recombination repair, a high-fidelity repair pathway. Unrepaired DNA double strand breaks or those repaired through error-prone pathways, progress to chromosomal damage, and chromosome instability. The latter is a common characteristic of Cr(VI)-exposed cells, and a hallmark of lung cancer. Although the mechanism of Cr(VI)-induced …

Passive Electronic Cigarette Exposure Initiates Squamous Metaplasia In A Developing 3d Human Tracheobronchial Epithelial Tissue In-Vitro Model, Edgar Rolon

Electronic Theses, Projects, and Dissertations

The prevalence of vaping has rapidly increased. ECs are often perceived as less harmful than tobacco cigarettes. A recent meta-analysis showed electronic cigarette (EC) aerosols adversely affected the respiratory system, similar to cigarette smoke, with some effects specific to EC use. Failure to prevent these alterations could lead to life-long comorbidities, and predisposition to respiratory diseases, including COPD and squamous cell carcinoma. While these effects are the result of active vaping, EC aerosols can also settle on indoor surfaces, be absorbed passively through the skin or orally, enter the blood stream, and subsequently expose internal organs, including the airway basal …

Stromal Cells In The Small Intestine: Physiology, Localization, Function, And Alterations Induced By Chronic Arsenic Exposure, Scott Ventrello

All Dissertations

Arsenic is a prevalent toxicant found to affect around 94 to 240 million individuals in over fifty countries who are exposed to levels above the EPA and WHO standard of 10 ppb. As one of WHO’s top ten chemicals of public health concern, it is linked to several chronic diseases including diabetes, obesity, cancers, and inflammatory bowel diseases. Arsenic increases inflammation and disrupts the intestinal barrier in the small intestine and colon. Further, previous studies found that arsenic decreased secretory cell lineage and stromal cell gene expression markers in the small intestine. Thus, our goal was to investigate arsenic’s effect …

Developing A Small Molecule To Inhibit Hsf1 Expression In Cancer And Evaluating Natural Genetic Variation In Small Molecule Toxicity., Michaela Kendal Foley

Theses and Dissertations

Each year cancer affects nearly 20 million people worldwide and genetic differences across populations can impact cancer onset and progression. Specifically, tumors with high levels of HSF1, the master regulator of the cytoprotective heat shock response (HSR), are correlated with poor patient outcomes in multiple cancers such as prostate, breast, and melanoma. Subsequently, the development of pharmacological inhibitors of HSF1 represents a promising strategy for anticancer therapeutics. Using a luciferase-based transcriptional reporter, two small molecule libraries were screened for inhibitors of HSF1 expression in human embryonic kidney cells, yielding ten compounds that decrease HSF1 expression. To identify if cancer lines …

Assessing The Behavioral Impact Of Pyridostigmine Bromide In Rats, Noah A. Martin

Honors Theses

Pyridostigmine bromide (PB) is an organophosphate (OP) nerve agent prophylactic used to protect warfighters against chemical warfare agents. OPs inhibit the neural enzyme acetylcholinesterase (AChE) in the brain. This leads to the buildup of acetylcholine, causing respiratory failure, seizures, and death. PB functions by inhibiting ~30% of peripheral AChE temporarily, protecting the enzymes so that the body is able to restore sufficient cholinergic function post-exposure. PB does not cross the blood-brain barrier, though it may still indirectly affect toxicity in the brain due to repeated AChE inhibition throughout treatment, or by inhibition of non-target ChE’s in the blood. The aim …

Effects Of Pfos On Zebrafish Dopaminergic Neurodevelopment, Allison G. Fletcher

Research and Creativity Symposium

Per- and polyfluoroalkyl substances (PFAS) are a group of environmental contaminants that cause disruptions to the nervous and endocrine systems. Perfluorooctanesulfonate (PFOS) is considered one of the most disruptive PFAS to the nervous system, and may disrupt neurodevelopment of the dopaminergic system, which has been linked to neurodevelopmental disorders like Attention Deficit/Hyperactivity Disorder (ADHD) in humans. I hypothesized that early life PFOS exposure disrupts the development of the dopaminergic system. To test this hypothesis, I exposed zebrafish to 0.05, 0.5, and 5.0 mg/L PFOS through 5 days of embryonic and larval development. To assess acute effects of PFOS on the …

Trace Element Contamination In The Coastal Gray Wolves Of Southeast Alaska, Miranda Brohman

All HCAS Student Capstones, Theses, and Dissertations

Gray wolves (Canis lupus), northern sea otters (Enhydra lutris) and salmon (Oncorhynchus spp.) play vital roles in southeast Alaska, yet all are exposed to trace element (TE) bioaccumulation. This study examines dietary patterns and TE accumulation in four northern Lynn Canal wolf populations (Douglas Island, Juneau, Gustavus, and Pleasant Island) using stable isotope analysis (SIA) (δ¹³C and δ¹⁵N) and TE assessments. SIA revealed that wolves in Juneau and Douglas Island primarily consumed terrestrial prey, whereas wolves in Gustavus and Pleasant Island exhibited enriched isotopic signatures indicative of a marine-based diet, particularly …

Zonal Hepatocellular Responses To Acute Ethanol: Impacts On Mitochondrial Function And Metabolism, Matthew T. Savoca

MUSC Theses and Dissertations

Background: Ethanol (EtOH) consumption causes hepatocellular mitochondrial depolarization (mtDepo) and mitophagy. Here, the Aims were to develop techniques to characterize sublobular hepatocellular metabolism and the distribution of mtDepo and mitophagy after acute EtOH. Methods: Wildtype and GFP-LC3 transgenic mice were treated with EtOH or vehicle and administered the covalently labeling mitochondrial membrane potential (ΔΨ) reporter, MitoTracker Red (MTR), and/or the non-covalent ΔΨ reporter, rhodamine 123 (Rh123), prior to intravital imaging, liver fixation, or hepatocyte isolation. After in vivo MTR, hepatocytes were isolated and sorted. Enrichment in E-cadherin (ECAD) and cytochrome P4502E1 in periportal (PP) and pericentral (PC) hepatocytes, respectively, validated …

Investigating Mercury Contamination In Urban Fish: Atomic Absorption Spectroscopy And Histological Analysis For Environmental And Human Health, Indy L. Cockrill, Ross Andrew

SPARK Symposium Presentations

Mercury contamination in aquatic ecosystems is a pressing environmental and public health concern, particularly in urban areas where industrial runoff and wastewater contribute to heavy metal accumulation. This study investigates mercury presence in fish from Richland Creek in Nashville, TN, by analyzing histological changes in liver and muscle tissues. Mercury bioaccumulates in aquatic food chains, potentially leading to physiological damage in fish and posing health risks to humans who consume contaminated seafood. While prior research has established mercury’s toxic effects, there is a need for localized studies assessing its presence in urban waterways. The hope is to find histological abnormalities …

Bacillus Coagulans 198 And L-Glutamine In Combination Attenuated Intestinal Mucositis In A 5-Fu-Induced Balb/C Mouse Model Via Modulation Of Gut Microbial Community Structure And Diversity, Wei-Jen Chen, Siou-Ru Shen, Wei-Hsuan Hsu, Bao-Hong Lee, Yu-Shan Wei, Hui-Fang Chu, Ming-Chung Tseng, Tang-Long Shen

Journal of Food and Drug Analysis

5-Fluorouracil (5-FU) disrupts intestinal cells and causes dysbiosis in the gut microbiota. This study explores the potential of Bacillus coagulans-198 (BC198) to mitigate gut microbiota imbalance and mucositis caused by 5-fluorouracil. L-glutamine is used to alleviate mucositis, and this study found that BC198 exhibits protective effects on the gut, including maintaining a healthy microbiota and reducing intestinal inflammation, regardless of whether L-glutamine is used in combination. Therefore, it can help reduce the deterioration of the gut environment caused by 5-fluorouracil. BC198 can be provided to cancer patients to prevent severe side effects, thereby improving their treatment outcomes and nutritional …

Protective Role Of Hsian-Tsao Ethanol Extract Against Body Fat, Serum Lipid Profiles, And Hepatic Lipid Profiles In High-Fat Diet-Fed Rats, Ching-Chang Cho, Gow-Chin Yen, Hsin-Yi Lee, Chun-Tse Tsai, Wei-Tang Chang, Chin-Lin Hsu

Journal of Food and Drug Analysis

This study investigated the preventive effects of a 40% ethanol extract of Hsian-tsao (40EEHT) on obesity in high-fat diet (HFD)-induced obese rats. Male Wistar rats were administered 0, 100, 200, or 500 mg/kg of 40EEHT, resulting in reduced body weight, total body fat, and hepatic tissue weight after 8 weeks. 40EEHT also decreased adipocyte size, improved lipid profiles, alleviated oxidative stress, and enhanced hepatic antioxidant enzyme activities. Additionally, it regulated fatty acid metabolism by reducing lipogenesis and increasing lipolysis and β-oxidation, suggesting its potential as an anti-obesity dietary supplement.

Xanthohumol As A Potential Therapeutic Strategy For Acute Myeloid Leukemia: Targeting The Flt3/Srpk1 Signaling Axis, Duan-Na Zhang, Wen-Ya Yang, Xiao-Xue Hu, Xiao-Min-Ting Song, Chuan-Jie Guo, Fu Peng, Yu-Zhi Li, Zhi-Xing Cao

Journal of Food and Drug Analysis

Xanthohumol (XN) is an isoprene chalcone found in hops (Humulus lupulus L.), a food ingredient with a wide range of pharmacological activities. The aim of this study was to reveal the therapeutic effect of XN on acute myeloid leukemia (AML) and the potential underlying molecular mechanism. Through network pharmacology analysis, molecular docking, and HTRF determination, XN was shown to inhibit the kinase activities of FLT3 and SRPK1 by targeting their ATP-binding domains, with IC₅₀ values of 1.51 ± 0.44 μM and 0.37 ± 0.15 μM, respectively. By inhibiting AML cell proliferation, promoting apoptosis, regulating autophagy, and inhibiting …

Within-Trial Cost-Effectiveness Of Novel Macrophage-Regulating Treatment On Wound Healing In Patients With Diabetic Foot Ulcers, Hsuan-Yu Su, Chen-Yi Yang, Yi-Hsin Chang, Shyi-Gen Chen, Jui-Ching Chen, Hui-Ju Ho, Huang-Tz Ou, Shihchen Kuo

Journal of Food and Drug Analysis

An M1/M2 macrophage-regulating treatment, ON101 cream, has shown its superior healing efficacy for diabetic foot ulcers (DFUs) versus standard absorbent dressing, according to a phase Ⅲ trial. Given its high cost, corroborating the economic value of ON101 treatment can facilitate clinical and policy decision-makings. This study sought to evaluate the cost-effectiveness of ON101 versus an absorbent dressing for patients with DFUs from Taiwan's healthcare sector perspective. This economic evaluation utilized effectiveness and cost data (in 2022 USD) from a randomized controlled trial of ON101, published literature, and Taiwan’s National Health Insurance program. Incremental cost-effectiveness ratio (ICER) against willingness-to-pay (WTP) threshold …

Method Development For The Determination Of Phosphine Residues In Foods, Shu-Wei Lin, Yu-Ting Liu, Ya-Chun Chou, Yu-Ching Hung, Shu-Han Chang, Ya-Min Kao, Su-Hsiang Tseng, Der-Yuan Wang

Journal of Food and Drug Analysis

Phosphine (PH₃) is a fumigant used for pest control of stored products and foods. In Taiwan, PH₃ has the maximum residue level (MRL) in 14 foods, including dried fruits, vegetables, spices, nuts, crops, roots, and tuber vegetables. In this study, gas chromatography/mass spectrometry coupled with a headspace sampler (HS-GC/MS) was used to determine the PH₃ content in foods. The stability of the PH₃ standard was evaluated either directly using the gas standard or indirectly using zinc phosphide (Zn₃P₂) with an acid. The optimal conditions for the headspace agitator were determined to …

A Deep Dive Into The Orchard Of Health: Exploring The Anti-Cancer And Anti-Aging Potential Of Apple Polyphenols, Li-Ching Chen, Han-Sheng Chang, Yuan-Soon Ho

Journal of Food and Drug Analysis

Apples, a ubiquitous and beloved fruit, harbor a treasure trove of bioactive compounds, with apple polyphenols (APs) taking center stage. This review delves into the latest scientific advancements illuminating the anti-cancer and anti-aging properties of APs. We dissect the intricate mechanisms by which APs combat cancer initiation, progression, and metastasis, highlighting their prowess in inducing apoptosis, inhibiting angiogenesis, and modulating cell signaling pathways. Furthermore, we explore the multifaceted ways APs combat aging, including their potent antioxidant and anti-inflammatory actions, DNA protective effects, and ability to modulate cellular processes like autophagy and metabolism. This comprehensive review underscores the therapeutic promise of …

Continuous Exposure To An Aversive Mixture: A Means Of Maintaining Aversion In Sheep Averted To Geigeria Ornativa O. Hoffm. (Vermeerbos) - An Assessment, Leendert D. Snyman

Poisonous Plant Research (PPR)

Establishing aversion to Geigeria ornativa only lasts for some time, after which the induced aversion disappears and sheep start eating G. ornativa again. This behavior is aggravated by the social influence of non-averted sheep in mixed grazing situations. Exposing sheep continuously to a so-called “aversive mixture”, containing an aversive substance (lithium chloride) and the sensory characteristics of the plant (hexane extract of G. ornativa) mixed with a tasty meal (maize meal), following an initial aversion treatment, resulted in sustained aversion to G. ornativa in the field. This method proved to be applicable to mixed grazing situations with averted and …

Clinical Importance Of Phenytoin Monitoring To Reduce Phenytoin-Related Toxicity In Saudi Patients With Epilepsy, Ghidaa Alwaf, Hussam Younis, Mohammed Al-Hartani, Alaa H. Falemban, Et.Al.

Saudi Toxicology Journal

Background: Phenytoin toxicity can result from overdose, dosage changes, drug interac-tions, or physiological alterations. Symptoms range from nausea and confusion to severe cases involving coma and seizures, though fatalities are rare. To date, no literature has been found concerning phenytoin monitoring in Saudi epileptic patients. This study is the first to inves-tigate phenytoin monitoring for toxicity prevention, optimal dosing, and adverse effect management in Saudi epileptic patients. Methods: A two-month, randomized, open-label, prospective monitoring study was conducted in Saudi epileptic patients treated with phen-ytoin. The patients (n=40) were subdivided into two groups (monitored and unmonitored) to check the prevalence of …

Cytotoxic, Genotoxic, And Metabolic Effects Of Dihydroxyacetone In Heart, Liver And Lung Models, Arlet Hernandez

All ETDs from UAB

Dihydroxyacetone (DHA) is a triose sugar found as an active ingredient in sunless tanning products (STPs) and by-product in electronic cigarettes (e-cigarettes). DHA can rapidly be absorbed into cells and tissues and incorporated into several metabolic pathways through its conversion into dihydroxyacetone phosphate (DHAP). Previous studies have shown that DHA promotes cytotoxicity and genotoxicity primarily characterized in skin models. The extent of these effects in systemic models is highly cell-type specific. Here we investigate the cytotoxic, genotoxic, and metabolic effects of DHA across several cell models. First, we investigated the effects of DHA in a metabolically active cell line, hepatocellular …

Improving The Safety Of N,N-Dimethylacetamide As A Potential Treatment For Preterm Birth Using A Vaginal Nanoformulation, Asad Mir

Theses and Dissertations

With no available treatment for preterm birth, the field of reproductive medicine has been repurposing small molecule candidates into vaginal nanoformulations as potential treatments for the condition. The commercial solvent N,N-Dimethylacetamide (DMA) has previously been shown to delay and prevent inflammation-induced preterm birth in a mouse model. A vaginal nanoformulation of DMA loaded into a self-nanoemulsifying drug delivery system (SNEEDS) was studied to see if it can also be efficacious. A side by-side histological comparison was done in the more pertinent tissues of the reproductive tract between the traditional formulation of DMA given intraperitoneally (IP) and the vaginal nanoformulation of …

The Effects Of Exosomes In Lead And Lps Induced Inflammation In Microglia, Yitzchak Lax

Theses and Dissertations

Exosomes are membrane bound subcellular vesicles formed through membrane budding of a cell and play important roles in cell-cell communication. Studies have demonstrated inflammatory changes in various cell types depending on the etiology of the exosomes such as exosomes from cancer cells or exosomes derived from mesenchymal stem cells. The purpose of this study was to determine the inflammatory consequences of exosomes in microglial cells following exposure to lead, lipopolysaccharides (LPS) and lead+LPS. The cultured mouse microglial cells were treated at 0.01 μM, 0.1 μM and 1 μM of lead,- three environmentally relevant levels and LPS was used at 10 …

Ms Environmental Biology Capstone: Evaluating Environmental Risks And Conflicts In Golf Course Landscapes, Meredith Boos

Regis University Student Publications (comprehensive collection)

1) This review investigates the relationship between pesticide use on golf courses and in agriculture to determine whether the adverse health effects documented in agricultural settings also apply to golf course environments. While the negative health effects from agricultural pesticide use are well established, golf courses use pesticides with greater frequency and intensity, suggesting a potentially higher exposure risk for both workers and players.

2) This study proposes methods to quantify pesticide bioaccumulation on golf courses and adjacent lands. We hypothesize that areas surrounding golf courses will exhibit a spatial gradient of pesticide accumulation, increasing with proximity to treated sites …

Gene Ontology Enrichment Reveals Pufa-Responsive Functional Themes In The Nucleus Accumbens Of Female Dba/2j Mice, Eman Mahjoub, Jennifer Wolstenholme Ph.D.

IRBEH/Spit for Science Publications and Presentations

No abstract provided.

Validating A Genetic Knockout Of Ninein In A Mouse Model, Jessikah M. Buys, E R. Gnatowski, L Vermuri, A Safeer, L Holmes, M. F. Miles

IRBEH/Spit for Science Publications and Presentations

Ninein (Nin) is a microtubule associated protein that has been previously characterized by the Miles Lab for regulating the anxiety-reducing (anxiolytic) effects of alcohol, which is thought to contribute to development of Alcohol Use Disorder (AUD). Previous studies in the lab have investigated the role of Nin deletion on anxiety and ethanol-related behaviors in a conditional knockout model. The following set of studies seek to validate this genetic model. The model was validated using three main methods: immunofluorescence, qRT-PCR, and gel electrophoresis. In PCR studies, Ninein was significantly reduced in cre-expressing animals compared to controls. Gel Electrophoresis confirmed this reduction …

Effects Of Psychedelics On Acute Nicotine Pharmacological Responses, Aleny Oros, Belle Buzzi, Julian Vaughn, Burhan Buttar, Javier Gonzalez-Maeso, M Imad Damaj

IRBEH/Spit for Science Publications and Presentations

Smoking is a major risk factor for illnesses, such as cancers, cardiovascular diseases and respiratory conditions. In smoking, nicotine activates nicotinic acetylcholine receptors in the brain region. Prolonged use of nicotine will desensitize these specific receptors and cause nicotine dependence, resulting in smokers to experience withdrawal symptoms, such as anhedonia, depression, stress, and craving, leading to relapse.2 As the rate cigarette smoking has declined over the years, it is not significantly entitled by the tremendous increase rate of e-cigarette use. In a previous study being published, life-time use of psychedelics is associated with lower nicotine dependence.1

Psychedelics, specifically psilocybin, which …

Investigating Plk1 In Pulmonary Fibrosis, Tempany Arbogast

Theses and Dissertations--Toxicology and Cancer Biology

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease, with a median survival of only 2–3 years following diagnosis. In the United States, the disease contributes to more than 40,000 deaths annually, underscoring its severe clinical burden. Alveolar type II (AT2) lung epithelial cells serve as progenitors that maintain alveolar integrity by replenishing epithelial populations and producing surfactants, while fibroblasts and myofibroblasts regulate the extracellular matrix and structural support. In pulmonary fibrosis (PF) injury to AT2 cells promotes cytokine and growth factor release, driving inflammation, fibroblast proliferation, myofibroblast accumulation, and excessive extracellular matrix deposition. Aberrant AT2 cell …

Identification Of Pharmacophore Modifications That Enhance Bmp-Receptor Agonism, An Investigation To Understand The Development Of Potential Therapeutic Interventions, Maleka T. Stewart

Theses and Dissertations

Bone morphogenetic proteins (BMPs) are the largest subfamily of the Transforming Growth Factor (TGF)-ß superfamily. BMPs are renowned for their pivotal role in cellular functions such as cell growth, apoptosis, and differentiation. Yet, BMPs have also been attributed to the maintenance of adult tissue homeostasis. BMPs elicit physiological function at the cell membrane via a heterotetrameric complex composed of two Type I and two Type II serine-threonine kinase BMP receptors. Activation of BMP transmembrane receptors results in activation of either canonical (Smad-dependent) and/or non-canonical (Smad-independent) signaling. Given the physiological importance of this intricate communication between receptor activation and induction of …

Navigating Wastewater: Minnesota Mining Wastewater Permit Challenges And Evolving Compliance Standards, Madelaine Adamich

Journal of Earth and Life Science

February of 2021 marked the beginning of Minnesota clearly establishing that groundwater qualifies as a Class 1 water in a legal battle involving United States Steel, the Minnesota Pollution Control Agency, WaterLegacy, Fond du Lac Band of Lake Superior Chippewa, the Minnesota Court of Appeals, and eventually the Minnesota Supreme Court (MNSC). Minnesota has a water classification system, as required by the federal Clean Water Act, with 7 classes of use. Class 1 waters are waters used for domestic consumption (MPCA 4, n.d.). According to Minnesota Statute § 7050.0220, the acceptable level for sulfate is 250 mg/L in Class 1 …

Potentiation Of Gelonin Cytotoxicity By Pulsed Electric Fields, Olga N. Pakhomova, Eleni Zivla, Giedre Silkuniene, Mantas Silkunas, Andrei G. Pakhomov

Bioelectrics Publications

Gelonin is a ribosome-inactivating protein with extreme intracellular toxicity but poor permeation into cells. Targeted disruption of cell membranes to facilitate gelonin entry is explored for cancer and tissue ablation. We demonstrate a hundreds- to thousands-fold enhancement of gelonin cytotoxicity by pulsed electric fields in the T24, U-87, and CT26 cell lines. The effective gelonin concentration to kill 50% of cells (EC₅₀) after electroporation ranged from <1 nM to about 100 nM. For intact cells, the EC₅₀ was unattainable even at the highest gelonin concentration of 1000 nM, which reduced cell survival by only 5–15%. For isoeffective electroporation treatments using 300 ns, 9 µs, and 100 µs pulses, longer pulses were more efficient at lowering gelonin EC₅₀. Increasing the electric field strength of 8, 100 µs pulses from 0.65 to 1.25 kV/cm reduced gelonin EC₅₀ from 128 nM to 0.72 nM. Conversely, the presence of 100 nM gelonin enabled a more than 20-fold reduction in the number of pulses required for equivalent cell killing. Pulsed electric field-mediated delivery of gelonin shows promise for hyperplasia ablation at concentrations sufficiently low to minimize or avoid systemic toxicity.