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Medical Toxicology Commons

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Melatonin And Its Metabolites Protect Human Melanocytes Against Uvb-Induced Damage: Involvement Of Nrf2-Mediated Pathways, Zorica Janjetovic, Stuart G. Jarrett, Elizabeth F. Lee, Cory Duprey, Russel J. Reiter, Andrzej T. Slominski 2017 The University of Alabama at Birmingham

Melatonin And Its Metabolites Protect Human Melanocytes Against Uvb-Induced Damage: Involvement Of Nrf2-Mediated Pathways, Zorica Janjetovic, Stuart G. Jarrett, Elizabeth F. Lee, Cory Duprey, Russel J. Reiter, Andrzej T. Slominski

Toxicology and Cancer Biology Faculty Publications

Ultraviolet light (UV) is an inducer of reactive oxygen species (ROS) as well as 6-4-photoproducts and cyclobutane pyrimidine dimers (CPD) in the skin, which further cause damage to the skin cells. Irradiation of cultured human melanocytes with UVB stimulated ROS production, which was reduced in cells treated with melatonin or its metabolites: 6-hydroxymelatonin (6-OHM), N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK), N-acetylserotonin (NAS), and 5-methoxytryptamine (5-MT). Melatonin and its derivatives also stimulated the expression of NRF2 (nuclear factor erythroid 2 [NF-E2]-related factor 2) and its target enzymes and proteins that play an important role in cell protection from different damaging factors including UVB ...


Lkb1 Inactivation Drives Lung Cancer Lineage Switching Governed By Polycomb Repressive Complex 2, Haikuo Zhang, Christine Fillmore Brainson, Shohei Koyama, Amanda J. Redig, Ting Chen, Shuai Li, Manav Gupta, Carolina Garcia-de-Alba, Margherita Paschini, Grit S. Herter-Sprie, Gang Lu, Xin Zhang, Bryan P. Marsh, Stephanie J. Tuminello, Chunxiao Xu, Zhao Chen, Xiaoen Wang, Esra A. Akbay, Mei Zheng, Sangeetha Palakurthi, Lynette M. Sholl, Anil K. Rustgi, David J. Kwiatkowski, J. Alan Diehl, Adam J. Bass, Norman E. Sharpless, Glenn Dranoff, Peter S. Hammerman, Hongbin Ji, Nabeel Bardeesy, Dieter Saur, Hideo Watanabe, Carla F. Kim, Kwok-Kin Wong 2017 Dana-Farber Cancer Institute

Lkb1 Inactivation Drives Lung Cancer Lineage Switching Governed By Polycomb Repressive Complex 2, Haikuo Zhang, Christine Fillmore Brainson, Shohei Koyama, Amanda J. Redig, Ting Chen, Shuai Li, Manav Gupta, Carolina Garcia-De-Alba, Margherita Paschini, Grit S. Herter-Sprie, Gang Lu, Xin Zhang, Bryan P. Marsh, Stephanie J. Tuminello, Chunxiao Xu, Zhao Chen, Xiaoen Wang, Esra A. Akbay, Mei Zheng, Sangeetha Palakurthi, Lynette M. Sholl, Anil K. Rustgi, David J. Kwiatkowski, J. Alan Diehl, Adam J. Bass, Norman E. Sharpless, Glenn Dranoff, Peter S. Hammerman, Hongbin Ji, Nabeel Bardeesy, Dieter Saur, Hideo Watanabe, Carla F. Kim, Kwok-Kin Wong

Toxicology and Cancer Biology Faculty Publications

Adenosquamous lung tumours, which are extremely poor prognosis, may result from cellular plasticity. Here, we demonstrate lineage switching of KRAS+ lung adenocarcinomas (ADC) to squamous cell carcinoma (SCC) through deletion of Lkb1 (Stk11) in autochthonous and transplant models. Chromatin analysis reveals loss of H3K27me3 and gain of H3K27ac and H3K4me3 at squamous lineage genes, including Sox2, ΔNp63 and Ngfr. SCC lesions have higher levels of the H3K27 methyltransferase EZH2 than the ADC lesions, but there is a clear lack of the essential Polycomb Repressive Complex 2 (PRC2) subunit EED in the SCC lesions. The pattern of high EZH2, but low ...


Effects Of Storage Time On Glycolysis In Donated Human Blood Units, Zhen Qi, John D. Roback, Eberhard O. Voit 2017 University of Kentucky

Effects Of Storage Time On Glycolysis In Donated Human Blood Units, Zhen Qi, John D. Roback, Eberhard O. Voit

Toxicology and Cancer Biology Faculty Publications

Background: Donated blood is typically stored before transfusions. During storage, the metabolism of red blood cells changes, possibly causing storage lesions. The changes are storage time dependent and exhibit donor-specific variations. It is necessary to uncover and characterize the responsible molecular mechanisms accounting for such biochemical changes, qualitatively and quantitatively; Study Design and Methods: Based on the integration of metabolic time series data, kinetic models, and a stoichiometric model of the glycolytic pathway, a customized inference method was developed and used to quantify the dynamic changes in glycolytic fluxes during the storage of donated blood units. The method provides a ...


Latexin Inactivation Enhances Survival And Long-Term Engraftment Of Hematopoietic Stem Cells And Expands The Entire Hematopoietic System In Mice, Yi Liu, Cuiping Zhang, Zhenyu Li, Chi Wang, Jianhang Jia, Tianyan Gao, Gerhard C. Hildebrandt, Daohong Zhou, Subbarao Bondada, Peng Ji, Daret K. St. Clair, Jinze Liu, Chang-Guo Zhan, Hartmut Geiger, Shuxia Wang, Ying Liang 2017 University of Kentucky

Latexin Inactivation Enhances Survival And Long-Term Engraftment Of Hematopoietic Stem Cells And Expands The Entire Hematopoietic System In Mice, Yi Liu, Cuiping Zhang, Zhenyu Li, Chi Wang, Jianhang Jia, Tianyan Gao, Gerhard C. Hildebrandt, Daohong Zhou, Subbarao Bondada, Peng Ji, Daret K. St. Clair, Jinze Liu, Chang-Guo Zhan, Hartmut Geiger, Shuxia Wang, Ying Liang

Toxicology and Cancer Biology Faculty Publications

Natural genetic diversity offers an important yet largely untapped resource to decipher the molecular mechanisms regulating hematopoietic stem cell (HSC) function. Latexin (Lxn) is a negative stem cell regulatory gene identified on the basis of genetic diversity. By using an Lxn knockout mouse model, we found that Lxn inactivation in vivo led to the physiological expansion of the entire hematopoietic hierarchy. Loss of Lxn enhanced the competitive repopulation capacity and survival of HSCs in a cell-intrinsic manner. Gene profiling of Lxn-null HSCs showed altered expression of genes enriched in cell-matrix and cell-cell interactions. Thrombospondin 1 (Thbs1) was a potential ...


Relb Expression Determines The Differential Effects Of Ascorbic Acid In Normal And Cancer Cells, Xiaowei Wei, Yong Xu, Fang Fang Xu, Luksana Chaiswing, David M. Schnell, Teresa Noel, Chi Wang, Jinfei Chen, Daret K. St. Clair, William H. St. Clair 2017 University of Kentucky

Relb Expression Determines The Differential Effects Of Ascorbic Acid In Normal And Cancer Cells, Xiaowei Wei, Yong Xu, Fang Fang Xu, Luksana Chaiswing, David M. Schnell, Teresa Noel, Chi Wang, Jinfei Chen, Daret K. St. Clair, William H. St. Clair

Toxicology and Cancer Biology Faculty Publications

Cancer cells typically experience higher oxidative stress than normal cells, such that elevating pro-oxidant levels can trigger cancer cell death. Although pre-exposure to mild oxidative agents will sensitize cancer cells to radiation, this pre-exposure may also activate the adaptive stress defense system in normal cells. Ascorbic acid is a prototype redox modulator that when infused intravenously appears to kill cancers without injury to normal tissues; however, the mechanisms involved remain elusive. In this study, we show how ascorbic acid kills cancer cells and sensitizes prostate cancer to radiation therapy while also conferring protection upon normal prostate epithelial cells against radiation-induced ...


A Novel Redox Regulator, Mntnbuoe-2-Pyp5+, Enhances Normal Hematopoietic Stem/Progenitor Cell Function, Yanming Zhao, Dustin W. Carroll, Y. You, Luksana Chaiswing, R. Wen, I. Batinic-Haberle, Subbarao Bondada, Ying Liang, Daret K. St Clair 2017 University of Kentucky

A Novel Redox Regulator, Mntnbuoe-2-Pyp5+, Enhances Normal Hematopoietic Stem/Progenitor Cell Function, Yanming Zhao, Dustin W. Carroll, Y. You, Luksana Chaiswing, R. Wen, I. Batinic-Haberle, Subbarao Bondada, Ying Liang, Daret K. St Clair

Toxicology and Cancer Biology Faculty Publications

The signaling of reactive oxygen species (ROS) is essential for the maintenance of normal cellular function. However, whether and how ROS regulate stem cells are unclear. Here, we demonstrate that, in transgenic mice expressing the human manganese superoxide dismutase (MnSOD) gene, a scavenger of ROS in mitochondria, the number and function of mouse hematopoietic stem/progenitor cells (HSPC) under physiological conditions are enhanced. Importantly, giving MnTnBuOE-2-PyP5+(MnP), a redox- active MnSOD mimetic, to mouse primary bone marrow cells or to C57B/L6 mice significantly enhances the number of HSPCs. Mechanistically, MnP reduces superoxide to hydrogen peroxide, which activates intracellular ...


Polyubiquitination Of Apurinic/Apyrimidinic Endonuclease 1 By Parkin, Timothy L. Scott, Christina A. Wicker, Rangaswamy Suganya, Bithika Dhar, Thomas A. Pittman, Craig Horbinski, Tadahide Izumi 2017 University of Kentucky

Polyubiquitination Of Apurinic/Apyrimidinic Endonuclease 1 By Parkin, Timothy L. Scott, Christina A. Wicker, Rangaswamy Suganya, Bithika Dhar, Thomas A. Pittman, Craig Horbinski, Tadahide Izumi

Toxicology and Cancer Biology Faculty Publications

Apurinic/apyrimidinic endonuclease 1 (APE1) is an essential protein crucial for repair of oxidized DNA damage not only in genomic DNA but also in mitochondrial DNA. Parkin, a tumor suppressor and Parkinson's disease (PD) associated gene, is an E3 ubiquitin ligase crucial for mitophagy. Although DNA damage is known to induce mitochondrial stress, Parkin's role in regulating DNA repair proteins has not been elucidated. In this study, we examined the possibility of Parkin‐dependent ubiquitination of APE1. Ectopically expressed APE1 was degraded by Parkin and PINK1 via polyubiquitination in mouse embryonic fibroblast cells. PD‐causing mutations in Parkin ...


Digital Pills To Measure Opioid Ingestion Patterns In Emergency Department Patients With Acute Fracture Pain: A Pilot Study, Peter R. Chai, Stephanie Carreiro, Brendan J. Innes, Rochelle K. Rosen, Conall O'Cleirigh, Kenneth Mayer, Edward W. Boyer 2017 Brigham and Women's Hospital

Digital Pills To Measure Opioid Ingestion Patterns In Emergency Department Patients With Acute Fracture Pain: A Pilot Study, Peter R. Chai, Stephanie Carreiro, Brendan J. Innes, Rochelle K. Rosen, Conall O'Cleirigh, Kenneth Mayer, Edward W. Boyer

UMass Center for Clinical and Translational Science Supported Publications

BACKGROUND: Nonadherence to prescribed regimens for opioid analgesic agents contributes to increasing opioid abuse and overdose death. Opioids are frequently prescribed on an as-needed basis, placing the responsibility to determine opioid dose and frequency with the patient. There is wide variability in physician prescribing patterns because of the lack of data describing how patients actually use as-needed opioid analgesics. Digital pill systems have a radiofrequency emitter that directly measures medication ingestion events, and they provide an opportunity to discover the dose, timing, and duration of opioid therapy.

OBJECTIVE: The purpose of this study was to determine the feasibility of a ...


Doxorubicin Cytotoxicity In A Human Proximal Tubular Epithelial Cell Line Was Attenuated By The Natural Product Resveratrol, Morghan Schuyler Getty 2017 Marshall University

Doxorubicin Cytotoxicity In A Human Proximal Tubular Epithelial Cell Line Was Attenuated By The Natural Product Resveratrol, Morghan Schuyler Getty

Theses, Dissertations and Capstones

The cancer chemotherapeutic agent doxorubicin (DOX), Adriamycin, is part of the treatment regimen for breast, ovarian, small cell lung cancer and acute/chronic lymphoid leukemia. Adverse effects associated with DOX are cardiotoxicity and nephrotoxicity. Interventions are needed to reduce DOX nephrotoxicity. Resveratrol (RES) is a phytochemical contained in grapes, berries and nuts, which possesses antioxidant and anticancer properties. This study tested the hypothesis that RES will attenuate DOX renal cytotoxicity in human noncancerous renal proximal tubular epithelial (HK-2) cells and that RES will reduce DOX mediated changes in mitochondrial function. HK-2 cells were plated and grown for 48 hours (h ...


Nucleotide Excision Repair: Impacts Of Environmental Carcinogens And Its Role In Cancer Susceptibility In Appalachian Kentucky, Nathaniel C. Holcomb 2017 University of Kentucky

Nucleotide Excision Repair: Impacts Of Environmental Carcinogens And Its Role In Cancer Susceptibility In Appalachian Kentucky, Nathaniel C. Holcomb

Theses and Dissertations--Toxicology and Cancer Biology

Lung cancer is a particularly devastating disease, accounting for the most deaths among all cancer types in the United States. Despite a reduction in the country’s smoking rates, cigarette smoking remains the number one risk factor for lung cancer. Additionally arsenic exposure, which occurs primarily through contaminated drinking water in the U.S., is associated with increased lung cancer incidence. The nucleotide excision repair (NER) pathway is critical for maintenance of genomic fidelity, removing DNA lesions that could otherwise promote DNA mutations and drive carcinogenesis. Tobacco smoking introduces significant amounts of DNA damage and produces characteristic DNA mutations found ...


Changes In Mitochondrial Homeostasis And Redox Status In Astronauts Following Long Stays In Space, Hiroko P. Indo, Hideyuki J. Majima, Masahiro Terada, Shigeaki Suenaga, Kazuo Tomita, Shin Yamada, Akira Higashibata, Noriaki Ishioka, Takuro Kanekura, Ikuya Nonaka, Clare L. Hawkins, Michael J. Davies, Daret K. St Clair, Chiaki Mukai 2016 Kagoshima University, Japan

Changes In Mitochondrial Homeostasis And Redox Status In Astronauts Following Long Stays In Space, Hiroko P. Indo, Hideyuki J. Majima, Masahiro Terada, Shigeaki Suenaga, Kazuo Tomita, Shin Yamada, Akira Higashibata, Noriaki Ishioka, Takuro Kanekura, Ikuya Nonaka, Clare L. Hawkins, Michael J. Davies, Daret K. St Clair, Chiaki Mukai

Toxicology and Cancer Biology Faculty Publications

The effects of long-term exposure to extreme space conditions on astronauts were investigated by analyzing hair samples from ten astronauts who had spent six months on the International Space Station (ISS). Two samples were collected before, during and after their stays in the ISS; hereafter, referred to as Preflight, Inflight and Postflight, respectively. The ratios of mitochondrial (mt) to nuclear (n) DNA and mtRNA to nRNA were analyzed via quantitative PCR. The combined data of Preflight, Inflight and Postflight show a significant reduction in the mtDNA/nDNA in Inflight, and significant reductions in the mtRNA/nRNA ratios in both the ...


The Role Of Nicotine, A7 Nicotinic Acetylcholine Receptors And Extracellular Matrix Remodeling In Pulmonary Fibrosis., Glenn Ward Vicary 2016 University of Louisville

The Role Of Nicotine, A7 Nicotinic Acetylcholine Receptors And Extracellular Matrix Remodeling In Pulmonary Fibrosis., Glenn Ward Vicary

Electronic Theses and Dissertations

The median survival for idiopathic pulmonary fibrosis (IPF) patients from diagnosis is a dismal 3 years. This condition is characterized by pulmonary fibroproliferation and excess production and disordered deposition of extracellular matrix (ECM) proteins resulting in obliteration of the original tissue architecture, loss of lung function and eventual death due to respiratory failure. The main hindrance to the development of effective treatments against pulmonary fibrosis is the late detection of its progression and is often of unknown cause. Tobacco smoke represents the most important environmental factor linked to the development of pulmonary fibrosis, with over 60% of IPF patients current ...


Analysis Of Rna Expression Of Normal And Cancer Tissues Reveals High Correlation Of Cop9 Gene Expression With Respiratory Chain Complex Components, Christina A. Wicker, Tadahide Izumi 2016 University of Kentucky

Analysis Of Rna Expression Of Normal And Cancer Tissues Reveals High Correlation Of Cop9 Gene Expression With Respiratory Chain Complex Components, Christina A. Wicker, Tadahide Izumi

Toxicology and Cancer Biology Faculty Publications

BACKGROUND: The COP9 signalosome, composed of eight subunits, is implicated in cancer genetics with its deneddylase activity to modulate cellular concentration of oncogenic proteins such as IkB and TGFβ. However, its function in the normal cell physiology remains elusive. Primarily focusing on gene expression data of the normal tissues of the head and neck, the cancer genome atlas (TCGA) database was used to identify groups of genes that were expressed synergistically with the COP9 genes, particularly with the COPS5 (CSN5), which possesses the catalytic activity of COP9.

RESULTS: Expressions of seven of the COP9 genes (COPS2, COPS3, COPS4, COPS5, COPS6 ...


Effect Of Genipin On Cisplatin- Induced Nephrotoxicity, Eglal Orner Mahgoub 2016 United Arab Emirates University

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 oxidase ...


Toxic Environmental Exposures And Kidney Health In Children., Darcy K. Weidemann, Virginia M. Weaver, Jeffrey J. Fadrowski 2016 Children's Mercy Hospital

Toxic Environmental Exposures And Kidney Health In Children., Darcy K. Weidemann, Virginia M. Weaver, Jeffrey J. Fadrowski

Manuscripts, Articles, Book Chapters and Other Papers

High-level exposures to a number of agents are known to have direct nephrotoxic effects in children. A growing body of literature supports the hypothesis that chronic, relatively low-level exposure to various nephrotoxicants may also increase the risk for chronic kidney disease (CKD) or accelerate its progression. In this review we highlight several environmental nephrotoxicants and their association with CKD in children and adolescents. We also discuss unique epidemiological challenges in the use of kidney biomarkers in environmental nephrotoxicology.


A Longitudinal Study Of Peripubertal Serum Organochlorine Concentrations And Semen Parameters In Young Men: The Russian Children's Study, Lidia Minguez-Alarcon, Oleg Sergeyev, Jane S. Burns, Paige L. Williams, Mary M. Lee, Susan A. Korrick, Luidmila Smigulina, Boris Revich, Russ Hauser 2016 Harvard T.H. Chan School of Public Health

A Longitudinal Study Of Peripubertal Serum Organochlorine Concentrations And Semen Parameters In Young Men: The Russian Children's Study, Lidia Minguez-Alarcon, Oleg Sergeyev, Jane S. Burns, Paige L. Williams, Mary M. Lee, Susan A. Korrick, Luidmila Smigulina, Boris Revich, Russ Hauser

Pediatric Publications

BACKGROUND: Exposures to endocrine disrupting chemicals during critical phases of testicular development may be related to poorer semen parameters. However, few studies have assessed the association between childhood organochlorine (OC) exposure and adult semen parameters.

OBJECTIVE: We examined whether peripubertal serum OC concentrations are associated with semen parameters among young Russian men.

METHODS: From 2003 to 2005, 516 boys were enrolled at age 8-9 years and followed for up to ten years. Serum OCs were measured in the enrollment samples using high-resolution mass spectrometry. At age 18-19 years, 133 young men provided one or two semen samples (256 samples) collected ...


The Future Of Teratology Research Is In Vitro, Jarrod Bailey, Andrew Knight, Jonathan Balcombe 2016 University of Newcastle-upon-Tyne

The Future Of Teratology Research Is In Vitro, Jarrod Bailey, Andrew Knight, Jonathan Balcombe

Jarrod Bailey, PhD

Birth defects induced by maternal exposure to exogenous agents during pregnancy are preventable, if the agents themselves can be identified and avoided. Billions of dollars and manhours have been dedicated to animal-based discovery and characterisation methods over decades. We show here, via a comprehensive systematic review and analysis of this data, that these methods constitute questionable science and pose a hazard to humans. Mean positive and negative predictivities barely exceed 50%; discordance among the species used is substantial; reliable extrapolation from animal data to humans is impossible, and virtually all known human teratogens have so far been identified in spite ...


Longitudinal Changes In Neurodevelopmental Outcomes Between 18 And 36 Months In Children With Prenatal Triptan Exposure: Findings From The Norwegian Mother And Child Cohort Study, Mollie E. Wood, Jean A. Frazier, Hedvig M.E. Nordeng, Kate L. Lapane 2016 University of Massachusetts Medical School

Longitudinal Changes In Neurodevelopmental Outcomes Between 18 And 36 Months In Children With Prenatal Triptan Exposure: Findings From The Norwegian Mother And Child Cohort Study, Mollie E. Wood, Jean A. Frazier, Hedvig M.E. Nordeng, Kate L. Lapane

Open Access Publications by UMMS Authors

OBJECTIVE: This study sought to determine whether changes in neurodevelopmental outcomes between 18 and 36 months of age were associated with prenatal exposure to triptan medications, a class of 5-HT receptor agonists used in the treatment of migraine.

METHOD: Using data from the Norwegian Mother and Child Cohort Study, a prospective birth cohort that includes nearly 40% of all pregnancies in Norway from 1999 to 2008, we identified 50 469 mother-child dyads who met inclusion criteria and were present for at least one follow-up assessment at 18 or 36 months postpartum. Neurodevelopment was assessed using the Child Behaviour Checklist, the ...


Lessons From Toxicology: Developing A 21st‑Century Paradigm For Medical Research, Gill Langley, Christopher P. Austin, Anil K. Balapure, Linda S. Birnbaum, John R. Bucher, Julia Fentem, Suzanne C. Fitzpatrick, John R. Fowle III, Robert J. Kavlock, Hiroaki Kitano, Brett A. Lidbury, Alysson R. Muotri, Shuang-Qing Peng, Dmitry Sakharov, Troy Seidle, Thales Trez, Alexander Tonevitsky, Anja van de Stolpe, Maurice Whelan, Catherine Willett 2016 Humane Society International

Lessons From Toxicology: Developing A 21st‑Century Paradigm For Medical Research, Gill Langley, Christopher P. Austin, Anil K. Balapure, Linda S. Birnbaum, John R. Bucher, Julia Fentem, Suzanne C. Fitzpatrick, John R. Fowle Iii, Robert J. Kavlock, Hiroaki Kitano, Brett A. Lidbury, Alysson R. Muotri, Shuang-Qing Peng, Dmitry Sakharov, Troy Seidle, Thales Trez, Alexander Tonevitsky, Anja Van De Stolpe, Maurice Whelan, Catherine Willett

Gill Langley, PhD

Biomedical developments in the 21st century provide an unprecedented opportunity to gain a dynamic systems-level and human-specific understanding of the causes and pathophysiologies of disease. This understanding is a vital need, in view of continuing failures in health research, drug discovery, and clinical translation. The full potential of advanced approaches may not be achieved within a 20th-century conceptual framework dominated by animal models. Novel technologies are being integrated into environmental health research and are also applicable to disease research, but these advances need a new medical research and drug discovery paradigm to gain maximal benefits. We suggest a new conceptual ...


Developing A More Clinically-Relevant Mouse Model Of Cisplatin-Induced Nephrotoxicity., Cierra N. Sharp 2016 University of Louisville

Developing A More Clinically-Relevant Mouse Model Of Cisplatin-Induced Nephrotoxicity., Cierra N. Sharp

Electronic Theses and Dissertations

Cisplatin is a nephrotoxic chemotherapeutic that causes acute kidney injury (AKI) in 30% of patients. Although recovery can occur after one episode of cisplatin-induced AKI, studies have indicated multiple episodes may lead to the development of chronic kidney disease (CKD), an irreversible disease with no current treatments. The standard mouse model of cisplatin-induced AKI consists of one, high dose of cisplatin (> 20 mg/kg) that is lethal to the animal three days later. This model doesn’t accurately reflect the repeated dosing regimen patients receive, and doesn’t allow for long-term outcome studies of pathologies associated with CKD. We have ...


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