Toxicology Commons^™

Garambullo (Myrtillocactus Geometrizans) Reduces Cell Viability Via Apoptosis And Inhibits Colony Formation In Ht-29 And Sw480 Colon Cancer Cell Lines., López-Alvarez Guadalupe Soledad, Gutierrez-Silerio Gloria Yareli, García-Solís Pablo, Morales-Bárcenas Rocio, Sánchez-Pérez Yesennia, Hernández-Puga Ana Gabriela, Vergara-Castañeda Haydé Azeneth

Journal of Food and Drug Analysis

Garambullo (Myrtillocactus geometrizans) is a Mexican fruit rich in bioactive phytochemicals. Its fermented extract (FEG), obtained after in vitro gastrointestinal digestion and fermentation, was evaluated in HT-29 and SW480 colorectal cancer cells. FEG reduced cell viability (IC50: 2985 and 3200 μg/mL, respectively) and induced apoptosis and necrosis. In 3D assays, FEG inhibited colony formation, with complete suppression in HT-29 cells. Molecular docking further suggested that butyric acid identified in FEG interacts with Caspase-3 and RIPK1. These findings support the antiproliferative and pro-death effects of FEG in colorectal cancer models.

Evaluation Of The Mechanism Of Cell Death After Exposure To Amorphous Silicon Dioxide Nanoparticles In Rat Pleural Mesothelial Cells And Golden Syrian Hamsters, Rachel P. Renda

Theses and Dissertations

Amorphous Silicon Dioxide Nanoparticles (SiO2 NPs) are widely used in the industrial processes, chemical, and cosmetics industries. Amorphous SiO2 NPs are abundant in the earth’s crust and can be released into the air through industrial and manufacturing activities. Such particles are overlooked and not as commonly studied when compared to their crystalline counterpart. Amorphous SiO2 NPs are pulmonary toxicants; however, the mechanism of toxicity is uncertain. In the current study, toxicity was assessed using both in vitro and in vivo systems to understand a possible mechanism of cell death. Rat Pleural Mesothelial Cells (RPMCs) were exposed to 50-800 μg/ml SiO2 …

Perfluorooctane Sulfonate (Pfos)-Induced Disruption Of Mitochondrial Activity And Cell Adhesion In Liver Cells, Phuong Dam Nam Tran

Graduate Theses/Dissertations

Perfluorooctane sulfonate (PFOS) is a persistent environmental pollutant associated with potential hepatoxic effects and other health risks. Despite its widespread distribution, the mechanisms underlying its toxicities remain to be fully understood. To investigate PFOS toxicology, my study utilized HepG2 and THLE-2 human hepatic cell models to replicate conditions reflecting PFOS accumulation in the liver. Cell viability, cell stress, and cell death assays were conducted to assess the toxicological influence of the chemical on both cell lines. Total RNA extraction was performed, followed by cDNA sequencing, and RT-qPCR. The XTT viability assay revealed a dose-dependent decrease in number of viable cells …

Combination Treatment Of Cordycepin And Radiation Induces Apoptosis Accompanied By Protective Autophagy In Tm3 Mouse Leydig Progenitor Cells, Yu-Yan Lan, Yi-Ping Lee, Wei-Ru Huang, Chun-Ying Yu, Lyh-Jyh Hao, Chun-Hung Lin, Bu-Miin Huang

Journal of Food and Drug Analysis

Leydig cells are anatomically located in the testicular interstitial tissue, and their main function is to produce and secrete testosterone and indirectly support spermatogenesis. We previously reported that the combination treatment of cordycepin and radiation can effectively induce Leydig tumor cell apoptosis through cell cycle arrest, caspase activation, endoplasmic reticulum (ER) stress, reactive oxygen species (ROS) accumulation, and DNA damage. However, there is still a lack of scientific evidence for the susceptibility of normal Leydig cells to the combination treatment. In the present study, mouse TM3 Leydig progenitor cells were used as a model to evaluate the effects and mechanisms …

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 …

The E-Liquid Flavorings Cinnamaldehyde, Vanillin, And Ethyl Vanillin Induce Cellular Stress Responses In Human Proximal Tubule (Hk-2) Epithelial Cells, Ashley J. Cox

Theses, Dissertations and Capstones

The use of electronic nicotine delivery systems (ENDS) has become popular in recent years as an alternative to traditional cigarettes. These devices heat and subsequently vaporize e-liquids for inhalation by the user, which allows for the delivery of ingredients such as flavorings, nicotine, and solvents through the vapor. Flavorings used in e-liquids are “generally recognized as safe” (GRAS) for consumption by the Food and Drug Administration (FDA), however there are currently no recommendations on safety regarding the inhalation of flavoring agents. While research characterizing effects of e-liquids and their flavorings is abundant in lung and respiratory tract models, few studies …

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

Undergraduate Research 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) …

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 …

Steamed Daylily Flower (Hemerocallis Fulva L.) Protected Cardiac And Hepatic Cells Against Ethanol Induced Apoptotic And Oxidative Damage, Sheng-Lei Yan, Wen-Tzu Wu, Mei-Chin Mong, Mei-Chin Yin

Journal of Food and Drug Analysis

Our previous study examined the phytochemical composition and bio-activities of raw daylily flower (Hemerocallis fulva L.). However, this plant food is usually served via heat process such as cooking in a soup. This study aimed to investigate the phytochemical profile and biofunctions of steamed daylily flower (SDF). The content of total phenolic acids, total flavonoids, total carotenoids, total anthocyanins and total triterpenoids in SDF aqueous extract was assessed. Normal cardiac and hepatic cells, H9c2 and L-02 cells, were used to evaluate the protective effects of SDF against ethanol. SDF concentrations of 0.25%, 0.5%, and 1% were applied to treat …

The Inhibitory Effect Of Quercetin-3-Glucuronide On Pulmonary Injury In Vitro And In Vivo, Pei-Rong Yua, Jen-Ying Hsu, Chiao-Yun Tseng, Jing-Hsien Chen, Hui-Hsuan Lin

Journal of Food and Drug Analysis

Pulmonary injury is defined as a progressive inflammation. Extensive pro-inflammatory cytokines are secreted from alveolus, associated with the production of reactive oxygen species (ROS) and apoptosis. The model of endotoxin lipopolysaccharide (LPS)-stimulated lung cells has been applied to mimic the pulmonary injury. Some antioxidants and anti-inflammatory compounds can be used as chemopreventive agents of pulmonary injury. Quercetin-3-glucuronide (Q3G) has been showed to exert antioxidant, anti-inflammatory, anti-cancer, anti-aging and anti-hypertension effects. The aim of the study is to examine the inhibitory potential of Q3G on pulmonary injury and inflammation in vitro and in vivo. Firstly, human lung fibroblasts MRC-5 cells pre-treated …

Induction Of Mitochondrial-Dependent Apoptosis By Essential Oil Of Toona Sinensis Root Through Akt, Mtor And Nf-Κb Signalling Pathways In Human Renal Cell Carcinoma Cells, Yu-Chi Chen, Chiao-Ling Hsieh, Bu-Miin Huang, Yungchia Chen

Journal of Food and Drug Analysis

Natural products have long been considered as a kind of complementary medicine. In this study, we investigate the apoptotic effect of essential oils of Toona sinensis roots (TSR) on human clear cell renal cell carcinomas (ccRCC). The sesquiterpene content of TSR essential oil was determined via GC/MS analysis. TSR decreased ccRCC cell viabilities, inducing ROS generation and reduction of the mitochondrial membrane potential. Moreover, TSR inhibited Bcl-2 and Hsp90 expression but increased PARP-1 cleavage and cytochrome c release. Akt, mTOR and NF-kB phosphorylation and HIF-a expression were all inhibited, which likely contributed to the anti-proliferative and anti-adhesive effects of TSR.

Loss Of The Na+/H+ Exchange Regulatory Factor 1 Results In Increased Susceptibility To Cisplatin-Induced Acute Kidney Injury., Adrienne M. Bushau-Sprinkle

Electronic Theses and Dissertations

Background. Acute kidney injury (AKI), an abrupt loss of kidney function which carries a high mortality and confers an increased risk of chronic kidney disease, develops in 30% of patients who receive cisplatin, a widely used chemotherapeutic agent [1], [2], [3]. The sodium hydrogen exchange regulatory factor isoform 1 (NHERF1) is a scaffolding protein that anchors multiple membrane proteins, in renal proximal tubules [4]. NHERF-1 deficient mice have aberrant localization of BBM proteins in intracellular compartments [5]. The investigators have recently demonstrated NHERF1 deficient proximal tubule cells have an underlying …

Chloroquine-Inducible Par-4 Secretion Is Essential For Tumor Cell Apoptosis And Inhibition Of Metastasis, Ravshan Burikhanov, Nikhil Hebbar, Sunil K. Noothi, Nidhi Shukla, James Sledziona, Nathália Araujo, Meghana Kudrimoti, Qing Jun Wang, David S. Watt, Danny R. Welch, Jodi Maranchie, Akihiro Harada, Vivek M. Rangnekar

Radiation Medicine Faculty Publications

The induction of tumor suppressor proteins capable of cancer cell apoptosis represents an attractive option for the re-purposing of existing drugs. We report that the anti-malarial drug, chloroquine (CQ), is a robust inducer of Par-4 secretion from normal cells in mice and cancer patients in a clinical trial. CQ-inducible Par-4 secretion triggers paracrine apoptosis of cancer cells and also inhibits metastatic tumor growth. CQ induces Par-4 secretion via the classical secretory pathway that requires the activation of p53. Mechanistically, p53 directly induces Rab8b, a GTPase essential for vesicle transport of Par-4 to the plasma membrane prior to secretion. Our findings …

Tenofovir Induced Nephrotoxicity: A Mechanistic Study, Rachel A. Murphy

Theses, Dissertations and Capstones

Tenofovir (TFV) is a reverse transcriptase inhibitor that is approved by the United States Food and Drug Administration (FDA) to treat HIV and chronic Hepatitis B. It has a long half-life, allowing for once a day dosing and is effective in treatment of both naive and experienced patients. It is administered orally as tenofovir disoproxil fumarate (TDF) and is deesterified in plasma to the active drug TFV. However, renal impairment is associated with its use; TFV can induce decreased glomerular filtration rate (GFR) and free calcitriol, renal failure, and Fanconi Syndrome. The exact mechanism of toxicity currently remains unknown, largely …