Access Type

Open Access Dissertation

Date of Award

January 2021

Degree Type

Dissertation

Degree Name

Ph.D.

Department

Pharmacology

First Advisor

Tracie Baker

Abstract

Approximately 2.9 billion prescriptions are written annually in the United States, with a multitude of biochemical actions, with 63151 tons used by food producing animals worldwide and an additional 55-77 million prescriptions written for companion animals. With increasing prescription and unknown toxicologic effects of many of these chemicals, zebrafish (danio rerio), an NIH approved human model, were used to model potentially health effects. Significant abnormalities were seen with extended duration metformin exposure from 4 hours post fertilization up to 5 days post fertilization, although short term metformin exposure for 24 hours at 4-5 days post fertilization did not lead to any significant abnormalities, along with neurobehavioral and transcriptomic changes. Similar results were found upon exposure to chemicals of emerging concern found in a wide variety of consumer products, namely Triclosan, triclocarban and 4-nonylphenol. These effects range from total mortality with either long- or short-term exposure at 100 and 1000 nM of triclosan, to abnormalities in uninflated swim bladder seen with long-term exposure to triclocarban and short-term exposure to 4-nonylphenol, and cardiac edema seen with short-term 4-nonylphenol exposure. Additionally, a significant number of genes involved in neurological and cardiovascular development were differentially expressed after the exposures, as well as lipid metabolism genes and metabolic pathways after exposure to each chemical. Finally, we examined the effects our own local water source, the Detroit River, had on indirectly exposed offspring. The Detroit River serves as the drinking water source for over 4 million people, and is polluted with a variety of contaminants such as pesticides (e.g. atrazine and metolachlor) and pharmaceuticals (e.g. metformin and salicylic acid. Previous research using a zebrafish (Danio rerio) model showed that early life exposure to these contaminants can lead to fertility problems, mortality problems, morphological abnormalities, and delayed puberty. We found a significant increase in the number of eggs produced by the exposure group, but also a significant increase in larval mortality and transcriptomic changes. Our work invites a re-evaluation of pharmaceuticals and personal care products found within our environment, as they can potentially lead to changes in behavior, gene expression and abnormalities have the potential to impact not only the local ecosystem, but human health as well.

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