Medical Toxicology Commons^™

Epc-Exs Improve Astrocyte Survival And Oxidative Stress Through Different Uptaking Pathways In Diabetic Hypoxia Condition, Manasi Suchit Halurkar, Jinju Wang, Shuzhen Chen, Ji Chen Bihl

Pharmacology and Toxicology Faculty Publications

Background: Hyperglycemia contributes to cardiovascular complications in patients with type 2 diabetes. We confirmed that high glucose (HG) induces endothelial dysfunction and cerebral ischemic injury is enlarged in diabetic mice. Stem cell-released exosomes have been shown to protect the brain from ischemic stroke. We have previously shown that endothelial progenitor cells (EPCs)-released exosomes (EPC-EXs) can protect endothelial cells from hypoxia/reoxygenation (H/R) and HG-induced injury. Here, we aim to investigate the effects of EPC-EXs on astrocytes under H/R and HG-induced injury and whether miR-126 enriched EPC-EXs (miR126-EPC-EXs) have enhanced efficacy. Methods: EPC-EX uptake and co-localization were measured by fluorescent microscopy using …

Exercise Improves Endothelial Function Associated With Alleviated Inflammation And Oxidative Stress Of Perivascular Adipose Tissue In Type 2 Diabetic Mice, Jinju Wang, Venkata Polaki, Shuzhen Chen, Ji Chen Bihl, Pasquale Pagliaro

Pharmacology and Toxicology Faculty Publications

Perivascular adipose tissue (PVAT), a type of adipose tissue that surrounds the blood vessels, has been considered an active component of the blood vessel walls and involved in vascular homeostasis. Recent evidence shows that increased inflammation and oxidative stress in PVAT contribute to endothelial dysfunction in type 2 diabetes (T2D). Exercise is an important nonpharmacological approach for vascular diseases. However, there is limited information regarding whether the beneficial effects of exercise on vascular function is related to the PVAT status. In this study, we investigated whether exercise can decrease oxidative stress and inflammation of PVAT and promote the improvement of …

Novel Mechanisms And Biomarkers In Alcohol-Induced Organ Injury., Christine E. Dolin

Electronic Theses and Dissertations

Background. Ethanol (EtOH) consumption is known to affect multiple organs; this is unsurprising, as the concentration of EtOH in the blood at relevant doses reaches the millimolar range. The overarching goal of this dissertation was to elucidate mechanisms of alcohol-induced organ injury, specifically the effects of alcohol on the hepatic extracellular matrix (ECM) proteome, the alcoholic hepatitis (AH) plasma peptidome, and the effects of alcohol on the renal cortex proteome and transcriptome. Methods. Mice were pair-fed ethanol-containing liquid diet chronically, and then some mice were administered lipopolysaccharide (LPS). Liver sections from these mice were processed in a series of increasingly …

Mechanistic Study Of Diatrizoic Acid Induced Proximal Tubule Cytotoxicity, Dakota Blake Ward

Theses, Dissertations and Capstones

Radiocontrast media (RCM) are necessary for many diagnostic procedures such as arteriography, percutaneous coronary intervention (PCI), and computed tomography. Contrast-induced acute kidney injury (CI-AKI) is the third most common cause of hospital-associated kidney damage accounting for 10-25% of cases worldwide. The mechanisms of contrast-induced renal impairment are not entirely known, but diminished renal hemodynamics, inflammatory responses, and direct cytotoxicity have been hypothesized. The purpose of this study was to investigate the mechanisms of direct cytotoxicity observed in HK-2 cells following treatment with diatrizoic acid (DA) and to determine the source of this damage. Mitochondrial function, endoplasmic reticulum (ER) stress, oxidative …

Extracellular Vesicles Released By Cardiomyocytes In A Doxorubicin-Induced Cardiac Injury Mouse Model Contain Protein Biomarkers Of Early Cardiac Injury, Chontida Yarana, Dustin W. Carroll, Jing Chen, Luksana Chaiswing, Yanming Zhao, Teresa Noel, Michael Alstott, Younsoo Bae, Emily V. Dressler, Jeffrey A. Moscow, D. Allan Butterfield, Haining Zhu, Daret K. St. Clair

Toxicology and Cancer Biology Faculty Publications

Purpose—Cardiac injury is a major cause of death in cancer survivors, and biomarkers for it are detectable only after tissue injury has occurred. Extracellular vesicles (EV) remove toxic biomolecules from tissues and can be detected in the blood. Here, we evaluate the potential of using circulating EVs as early diagnostic markers for long-term cardiac injury.

Experimental Design—Using a mouse model of doxorubicin (DOX)-induced cardiac injury, we quantified serum EVs, analyzed proteomes, measured oxidized protein levels in serum EVs released after DOX treatment, and investigated the alteration of EV content.

Results—Treatment with DOX caused a significant increase in …

Role Of Oxidized Extracellular Vesicles As Early Biomarkers And Inflammatory Mediators In Chemotherapy-Induced Normal Tissue Injury, Chontida Yarana

Theses and Dissertations--Toxicology and Cancer Biology

Significant advances in the efficacy of cancer therapy have been accompanied by an escalation of side effects that result from therapy-induced injury to normal tissues. Patients with high grade cancer or metastasis are often treated with chemotherapy, 50% of which are associated with reactive oxygen species generation and cellular oxidative stress. Heart is the normal tissue most susceptible to chemotherapy-induced oxidative stress and heart disease is the most common leading cause of death in cancer survivors. However, early and sensitive biomarkers to identify heart disease are still lacking. Extracellular vesicles (EVs) are released from cells during oxidative stress and send …

Chemotherapy-Induced Tissue Injury: An Insight Into The Role Of Extracellular Vesicles-Mediated Oxidative Stress Responses, Chontida Yarana, Daret K. St. Clair

Toxicology and Cancer Biology Faculty Publications

The short- and long-term side effects of chemotherapy limit the maximum therapeutic dose and impair quality of life of survivors. Injury to normal tissues, especially chemotherapy-induced cardiomyopathy, is an unintended outcome that presents devastating health impacts. Approximately half of the drugs approved by the Food and Drug Administration for cancer treatment are associated with the generation of reactive oxygen species, and Doxorubicin (Dox) is one of them. Dox undergoes redox cycling by involving its quinone structure in the production of superoxide free radicals, which are thought to be instrumental to the role it plays in cardiomyopathy. Dox-induced protein oxidation changes …

Effect Of Genipin On Cisplatin- Induced Nephrotoxicity, Eglal Orner Mahgoub

Theses

Cisplatin (CSP) is a potent and widely used chemotherapeutic agent. However, clinical efficacy of CSP is compromised due to the elicitation of nephrotoxicity and ototoxicity. In this study, I have investigated the nephroprotective effects of a phytochemical – genipin (GP) isolated from gardenia flower (Gardenia jasminoides), on a murine model of cisplatin-induced nephropathy. CSP-induced renal tissue injury was characterized by elevated levels of serum blood urea nitrogen (BUN), creatinine (Cr) and cystatin-C. In addition, levels of kidney injury molecule-1 (KIM-1) were increased in the renal tissues of CSP administered animals. CSP also induced renal oxidative stress, evidenced by increased NADPH …

Didox Modulates Reactive Oxygen Species Production And Inflammatory Events Induced By Lipopolysaccharide (Lps) And Aryl Hydrocarbon Receptor (Ahr) Ligands In Raw 264.7 Murine Macrophages., Thabe Matsebatlela

All Dissertations

Aberrant activation of macrophages during inflammation results in oxidative burst release of reactive oxygen and reactive nitrogen species (ROS/RNS) which are widely accepted to participate in pathogenesis of cancer, cardiovascular disease, atherosclerosis, hypertension, ischemia/reperfusion injury, diabetes mellitus, neurodegenerative diseases (Alzheimer's disease and Parkinson's disease), rheumatoid arthritis, and ageing. It is demonstrated here that Didox (3,4-Dihydroxybenzohydroxamic acid) possesses antioxidative and anti-inflammatory properties that can protect against inflammation and oxidative stress induced by lipopolysaccharide (LPS) and aryl hydrocarbon receptor (AHR) ligands (PCB126, E804, and IO) in Raw 264.7 murine macrophages. In brief, it is demonstrated here that Didox inhibits LPS-induced oxidative stress, …