Examination of diesel and biodiesel exhaust exposure induced disruption of arachidonic acid metabolism Public Deposited

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  • March 19, 2019
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  • Bhavaraju, Laya
    • Affiliation: School of Medicine, Curriculum in Toxicology
Abstract
  • Diesel combustion emissions contributes a large amount of particulate matter found in air pollution collected in high-traffic urban areas. Current epidemiology studies indicate a strong association between traffic and increased susceptibility to adverse respiratory and cardiovascular events. Current air quality initiatives have introduced biodiesel combustion as an alternative for diesel fuel to reduce particulate emissions. Incomplete biodiesel (BD) combustion emissions particulate matter analysis has detected the presence of unique emissions components, such as fatty acid methyl esters. However, biological activity of BD exhaust emissions have yet to be studied unlike diesel exhaust. Particle extraction based cellular-response studies have challenges with collection bias and sample loss. In this research, an improved extraction method was established with both diesel and BD exhaust particle for use in cell culture exposure assessments. Critical comparisons of BD and diesel particle extractions allowed for assessment of composition based response alterations of arachidonic acid (AA) metabolism. Multiple cellular functions are regulated by AA metabolites including inflammation and vascular tone. Endothelial cells regulate vascular tone by releasing lipid signaling molecules (PGI2 and PGF2a) to signal relaxation of smooth muscle cells. Alveolar macrophages (AM) release prostaglandins (PGE2) indicating cellular inflammation response. The work in this dissertation compared in vitro responses of diesel and BD exposure with alterations to AA metabolism. We initially observed the AA metabolism changes with response to BD and diesel emission particles in AM. The significant changes in prostaglandin production and release from BD relative to diesel led to further assessment of AA metabolite production alterations in endothelial cells. The mechanistic response of BD extract was addressed with human umbilical cord endothelial cells (HUVECs) and the findings revealed a reduction in prostaglandins and prostacyclins relative to diesel exposure. The increased incorporation of AA back into the phospholipid membranes by acyltransferase was associated with BD exposure resulting in reduction of prostacyclin and prostaglandins. Cumulatively these studies, increase the depth of knowledge of diesel and BD induced disruption of AA metabolism. Thus, signifying the composition of exhaust can induce differential cellular responses of lipid mediators affecting AM inflammation signaling and the HUVECs lipid remodeling pathways.
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  • In Copyright
Advisor
  • Taylor, Joan
  • Church, Frank C.
  • Madden, Michael
  • Kodavanti, Urmila
  • Jaspers, Ilona
Degree
  • Doctor of Philosophy
Degree granting institution
  • University of North Carolina at Chapel Hill Graduate School
Graduation year
  • 2015
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  • Chapel Hill, NC
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