Date of Award
2008
Degree Type
Thesis
Degree Name
Master of Science
Program
Physiology and Pharmacology
Supervisor
Dr. Michael J. Rieder
Second Advisor
Dr. Jack R. Bend
Third Advisor
Dr. David J. Freeman
Abstract
Variations in formation and disposition of N-hydroxylamine metabolite (SMX-NHOH) of sulfamethoxazole (SMX) and non-enzymatic oxidation to W-nitroso derivative (SMX-NO) are thought to be important in the pathogenesis of idiosyncratic drug reactions (IDRs), and produce reactive oxygen and nitrogen species (ROS/RNS). We investigated the potential attenuation of IDRs by complementary antioxidant therapy in sulphonamide-mediated IDRs using SMX-NHOH toxicity in Jurkat £6.1 cells. Baicalein, by chelating iron, and crocetin, by scavenging free radicals, are two antioxidant compounds of plant origin. We found that baicalein and crocetin (5 and 50 pM) potentiated the effect of 400 pM SMX-NHOH on markers of viability, ROS, and mitochondrial depolarization. Supplementation with baicalein and crocetin were of little benefit, and even deleterious in Jurkat £6.1 cells in some instances. However, the idea of complementary antioxidant therapy should not be completely discarded and data from these results suggest a duality between pro-oxidant and antioxidant effects of baicalein and crocetin.
Recommended Citation
Yip, Cindy S., "EFFECT OF ANTIOXIDANTS ON REACTIVE METABOLITE TOXCITY" (2008). Digitized Theses. 4196.
https://ir.lib.uwo.ca/digitizedtheses/4196