Document Type

Open Access Thesis

Embargo Period

9-1-2017

Degree Program

Public Health

Degree Type

Master of Science (M.S.)

Year Degree Awarded

2016

Month Degree Awarded

September

Advisor Name

Alicia

Advisor Middle Initial

R

Advisor Last Name

Timme-Laragy

Abstract

Butylparaben (Butyl p-hydroxybenzoic acid) is a widely used cosmetic and pharmaceutical preservative that has been recently shown to induce oxidative stress and have endocrine disrupting effects in rodents, and promote adipocyte conversion of human adipose cells. Embryonic development is extremely sensitive to oxidative stress due to changes in cell growth, development and differentiation that occur during this life stage. Fluctuations in redox potentials play critical roles in normal embryonic development by guiding these cell signaling, cell-fate decisions and apoptosis. The most prevalent endogenous antioxidant that defends against oxidative stress is glutathione (GSH), which scavenges reactive oxygen species. The low antioxidant capacity of pancreatic beta cells suggests that they are sensitive target tissues of oxidative stress; this has yet to be investigated during embryonic development. Here, we aim to 1) determine whether embryonic exposure to butylparaben prompts structural and functional changes in the developing endocrine pancreas and 2) determine whether oxidative stress may be involved. Transgenic insulin-GFP zebrafish embryos were treated daily with 250, 500, 1,000 and 3,000 nM butylparaben starting at 3 hours post fertilization (hpf). Pancreatic islet and whole embryo morphological development were examined daily until 7 days post fertilization (dpf). Redox potentials were measured at 24 and 28 hpf using HPLC. Area of the pancreatic islet increased over time with increasing butylparaben exposure in a dose-dependent manner by as much as a 55% increase in islet area at 3 dpf when compared to controls. Butylparaben concentrations of 500 and 1,000 nM increased GSH by 10 and 40%, respectively, and decreased oxidized glutathione disulfide by 37 and 59%. GSH redox potentials were only significant in embryos collected at 28 hpf and became more reduced with 500 and 1,000 nM butylparaben exposure, decreasing redox potentials by 7 and 18 mV, respectively. Cysteine redox potentials also became more reduced, decreasing by 17 and 28 mV. Our data show that butylparaben-induced redox potential disruptions that may be responsible for the effects on pancreatic islet structure and function, but further studies are needed to determine how and if that directly affects pancreas development.

First Advisor

Alicia R. Timme-Laragy

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