Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Physiology and Pharmacology

Supervisor(s)

Dr. Michael Rieder

Abstract

As sulfonamide hypersensitivity reactions are serious clinical problem, it is necessary to determine which patients tolerate therapy and which patients are at risk. Although the exact pathogenesis of these reactions remains unclear, the imbalance in the production and detoxification of reactive sulfamethoxazole (SMX) metabolites appears to be important in the propagation of these reactions. It is known that these reactive metabolites can cause lymphocytes toxicity and produce reactive oxygen species (ROS) which can damage proteins, lipids, and DNA. The hypothesis of this research is that there are differences in cytotoxicity and expression of oxidative stress to reactive SMX metabolites in the cells of patients who have sustained sulfonamide hypersensitivity reactions versus the cells of controls or sulfonamide tolerant patients. Sulfa hypersensitive patients were found to express high degrees of cell death and more ROS accumulation. This finding indicates that the biotransformation of SMX to its reactive metabolites could be the reason for cytotoxicity, and the oxidative Stress can be a mediator for cell death and inducing allergy reactions.


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