Date of Award

5-1-2023

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Chemistry

First Advisor

Dr. Rafaela Feresin

Abstract

There has been a significant rise in the use of electronic cigarettes (e-cigarettes), devices which deliver vaporized nicotine to the lungs. Due to their recent arrival on the market, evidence of their health effects is scant. Acute e-cigarette exposure induces pulmonary and systemic oxidative stress in e-cigarette users and contributes to vascular endothelial dysfunction through reduction in nitric oxide (NO) levels. Polyphenols, such as cyanidin-3-glucoside and ellagic acid, which are abundant in blackberries (BL), mitigate lung and cardiovascular damage. The goal of this study was to determine the effects of e-cigarette exposure on pulmonary, cardiac, and vascular pathologies and to determine whether BL have the potential to mitigate these detrimental effects. Mice were fed a diet supplemented with or without 5% freeze-dried blackberry (w/w) for 16 weeks. Daily e-cigarette exposure (1 h, 5 days/week) began on week 4. Human microvascular endothelial cells were treated with BL polyphenol extract and e-cigarette condensate to determine the direct effects on the vascular endothelium. Results show that 12-week e-cigarette exposure does not induce changes in blood pressure in mice but does induce oxidative stress in the aorta. E-cigarette exposure decreased NO bioavailability in vivo and in vitro likely due to increased superoxide production resulting from increased expression of inducible NO synthase (NOS), NADPH oxidases and xanthine oxidase (XO) in the endothelium. Additionally, e-cigarettes reduced the phosphorylation of endothelial NOS, contributing to decreases in NO. Mice supplemented with BL were protected against decreases in NO and BL pre-treatment in vitro reduced superoxide production. E-cigarettes also induced pro-oxidant protein expression in the lung and heart, an effect blackberry was unable to attenuate. These studies demonstrate the contribution of e-cigarettes to cardiopulmonary pathologies through an increase in superoxide producing enzymes. BL polyphenols mitigate these deleterious effects in the vasculature but were not effective at attenuating oxidative stress and inflammation induced by e-cigarettes in the lung or heart. Further studies should explore the role of polyphenol rich foods in protecting against cardiopulmonary conditions induced by e-cigarette use and explore their use in the recovery period post-e-cigarette cessation to properly align with current public health messaging.

DOI

https://doi.org/10.57709/35348604

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