Date of Award

2024-05-01

Degree Name

Doctor of Philosophy

Department

Environmental Science and Engineering

Advisor(s)

Felicia S. Manciu

Abstract

This study employs a combination of theoretical and experimental analysis to spectroscopically investigate the biomechanistic structure relationship and therapeutic effects of the Nordihydroguaiaretic Acid (NDGA) chemical derived from the Larrea Tridentata plant. These relationships are crucial for understanding NDGA's efficacy in disease prevention, treatment, and potential toxicological effects. While the medicinal and antiviral properties of the NDGA have been studied extensively, there remains a gap in optically identifying and reporting its structural changes. The current research successfully reveals evident trends in NDGA's vibrational signatures, particularly highlighting the absence of the Raman feature at 780 〖cm〗^(-1) as indicative of a fully oxidized structural form contributing to its bio-toxicity alongside ortho-quinone accumulation. Additional characteristic signatures of these toxic forms include the Raman lines at 1582 and 1698 〖cm〗^(-1) and the IR vibrational line at 1680 〖cm〗^(-1). By elucidating these morphological changes, this study offers valuable insights for the development and implementation of new drugs. Connecting evidence in supporting this statement is the second part of the study, where the NDGA was used for glioblastoma (GBM) treatment. Again, combined experimental Raman and statistical analyses were implemented to detect the drug effect on GBM-treated human cells. As a potential therapeutic agent, NDGA is a reactive oxygen species (ROS) scavenger and antioxidant. This phenolic lignan had positive effects on multi-organ malignant tumor reduction and inhibition. Although the drug concentrations were beyond the Raman capability limit of their detection, the results show a decrease in altered protein content and ROS-damaged phenylalanine upon NDGA administration. The use of phenylalanine as a biomarker for differentiating across samples and evaluating NDGA's effectiveness is a new finding discussed here. The creation of lipid droplets and a decline in the altered protein content indicate that treatment with a low dosage of NDGA over long periods reduces abnormal lipid-protein metabolism. The knowledge acquired via this research is significant for comprehending both the positive and negative bio-effects of NDGA as a potential treatment for brain cancer.

Language

en

Provenance

Received from ProQuest

File Size

87 p.

File Format

application/pdf

Rights Holder

Jose Arturo Guerrero

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