Date of Award
Doctor of Philosophy
Environmental Science and Engineering
Many environmental toxicants are known to increase free-radical production, which can create cellular havoc and lead to a myriad of ailments. Antioxidants can be used to ameliorate the prevalence of free radicals, potentially serving as prophylactics against radical-induced disorders. Many exogenous antioxidants are phytochemicals in origin, such as ascorbic acid, gallic acid, and ellagic acid. Some of these antioxidants can be found in traditional medicine, like tanshinone and brazilin, which have been studied and are known to have low cytotoxicity. Here we test the radical rescue capacity of a selected group of phytochemical antioxidants on protein rescue models. Specifically, our focus is on neurodegenerative disorders which hallmark is protein aggregation, such as Alzheimer's Disease ("AD"). Although the onset of this disorder is not well understood, protein radical damage and protein aggregation cause cell cytotoxicity and subsequent neurodegeneration; therefore, ameliorating radical damage can alleviate the onset of protein damage and aggregation. We will elicit protein radical damage to test the efficacy of select compounds in eliciting a bioactive response to protein damage and fibrilization. In addition, we will introduce a protein delivery system with the objective of increasing the bioavailability of the phytochemicals and potentially employ them in prophylactic treatments. Results of these assays indicate a potent antioxidant effect from ascorbic acid and ellagic acid in the novel protein rescue models, in contrast to the phytochemicals found in traditional medicine, which elicit a weak antioxidant response, providing a more significant contribution via their conjugated systems in fibril inhibition and disassociation. Results from the protein-ligand interaction in the delivery system are greatly favored by hydrophobic interactions stemming from the protein cavity.
Received from ProQuest
Zubia, Emmanuel, "Antioxidant Intervention In Radical-Induced Protein Damage" (2020). Open Access Theses & Dissertations. 3207.