Date of Award

2017

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Cellular and Molecular Pathobiology

College

College of Graduate Studies

First Advisor

John Bowden

Second Advisor

John Baatz

Third Advisor

John Kucklick

Fourth Advisor

Gavin Naylor

Fifth Advisor

Demetri Spyropoulos

Abstract

Eicosanoids are bioactive lipid messengers that mediate the immune response in a variety of different cell types. Due to their structural, as well as biological diversity, lipidomics technology for the direct measurement of eicosanoids is needed to provide a more systematic look into their actions in cells and tissues. Use of eicosanoids as indicators of inflammation in environmental samples is limited, and this body of work aimed to create a reproducible methodology for their comprehensive analysis in sentinel species. Sentinel species represent a way to examine inflammation and oxidative stress within the environment. In the first two research chapters, we developed a method to quantify 100 biologically active eicosanoids in environmental samples using American alligator and chicken chorioallantoic membrane (CAM) to validate our methodology. We demonstrated that oviparous CAM was similar to viviparous membranes in the increased prostaglandin concentrations prior to hatching (birth), and highlighted the potential use of CAM tissue as a sentinel model to study the mammalian placenta. In Chapter 4, we tested whether Dioctyl sodium sulfosuccinate (DOSS), a putative obesogen, altered eicosanoid profiles in human pluripotent stem cells. In this chapter we demonstrated that DOSS induced an inflammatory phenotype in human pluripotent stem cells (increased prostaglandin production and cyclooxygenase-2 activity). In chapters 5, we investigated an inflammatory disease (pansteatitis) in environmental samples. Our experiments highlighted the type of inflammation (oxidative stress) found in tilapia; we are the first to describe oxidized metabolites of linoleic acid in pansteaitits-affected adipose tissue. We also examined heavy metals in the tilapia sampled and found increased aluminum in pansteatitis-affected fish, with decreased zinc, copper, selenium, cobalt and arsenic. Jointly, this provides core information that will serve to guide future experimental inquiry into the causative factors of pansteatitis in aquatic vertebrates in this region. The work presented within this dissertation demonstrates a methodology for the investigation of eicosanoids and fatty acids as markers of inflammation and oxidative stress in multiple biological matrices.

Rights

All rights reserved. Copyright is held by the author.

Download

Share

COinS