Date of Award

2019

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Biology

First Advisor

Eugene R. Delay

Abstract

Chemotherapeutics are used extensively to treat cancer patients and often induce adverse effects, including taste dysfunctions. Disturbances in taste are detrimental to the overall well-being of cancer patients, causing malnutrition and weight loss that aggravate their condition even further. Inflammation due to an infection of the taste sensory system as previously shown, has detrimental effects on the taste sensation. Our study focused on if chemotherapy induced an inflammatory response in the taste buds using cyclophosphamide (CYP), a pro-drug. Once metabolized by the P450 enzyme complex, its primary metabolite functions as an alkylating agent, involved in inhibiting cell replication cycle and cell death. We used immunohistochemistry and fluorescent microscopy to analyze and observe the expression of the pro-inflammatory cytokine TNF-α in different types of taste sensory cells. Previously we found that a sulfhydryl cytoprotective drug, amifostine, can prevent taste bud damage and therefore we asked if it could prevent an inflammatory response. Our research observed an inflammatory response in both Type II and Type III cells in taste buds of fungiform and circumvallate papilla. Type II cells showed a peak response at 8- and 24-hour post-CYP injection whereas Type III cells had a peak expression at 24-hour post-CYP injection in the circumvallate papillae. Pre-treatment with amifostine appeared to prevent an inflammatory response within taste buds from CYP induced cytokine response. Identifying inflammation as a potential factor in taste related disorders could help clinicians develop better treatment modalities such as cytoprotective drugs preventing chemotherapy induced long term adverse effects such as malnutrition. In the future, we would like to expand our research to investigate expression of other pro-inflammatory cytokines and possible signaling mechanisms that could be responsible for CYP-induced inflammatory response in Type III cells.

Language

en

Number of Pages

99 p.

Available for download on Sunday, October 10, 2021

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