Date of Award

2011

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Environmental Science

First Advisor

Waterman, Jenora T.

Abstract

Nanotoxicology is the study of the potential toxic effects of anthropogenic and biogenic nanostructures on living organisms. The influence of nanostructures such as nanoparticles on the human airway has gained interest due to increased susceptibility of translocation into other regions of the body. Adverse effects such as oxidative stress and inflammation have been found after the inhalation of airborne nanoparticles in airway epithelial cells. Oxidative stress and inflammation in mice models have been attenuated through the consumption of antioxidant containing plant compounds called phytochemicals. In this dissertation, we have evaluated the hypothesis that nanoparticles regardless of origin can elicit oxidative stress and inflammation; however sorrel (Hibiscus sabdariffa) extract (rich in antioxidants) can minimize these effects. This study investigated markers of oxidative stress and inflammation through proteomic, genomic, and cytokine profile analyses following anthropogenic and biogenic nanoparticle exposure in vitro and the level of cellular response from antioxidant treatments. The overall goal of this study was to perform a comprehensive analysis of the molecular alterations mediated by nanoparticles on the human airway epithelium and substantiate a novel therapeutic antioxidant treatment. Results revealed that swine confinement facility dust upregulated expression of proinflammatory mediator genes in NHBE cells such as prostaglandin endoperoxide synthase 2 or COX-2 after 4hrs of exposure. Each of these genes was validated with Western blot immunoassay. Antioxidant treatments of sorrel (Hibiscus sabdariffa) attenuated the expression of GPX-2, PTGS2 or COX-2, and DUOX1 genes at 4hrs and 24hrs. In regards to the effect of magnesium biomaterials on normal human bronchial epithelial cells, no significant modulation of pro-inflammatory mediators such as COX-2 on IκBα were found in genomic profile or proteomic analysis using qPCR and Western blot respectively. Additionally, mucin and cytokine production were unaffected and cell migration was enhanced by magnesium wire exposure for 24hr. Cellular assays of osteoblasts exposed to varying concentrations of different hydrophilic nanoclays induced high levels of cytotoxicity and interfered with the catalytic properties of assay reagents. Thus, nanoparticles from biogenic origins induced oxidative stress and inflammation in airway epithelium and anthropogenic nanoparticles imposed high cytotoxicity; however magnesium biomaterials did not encourage oxidative damage.

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