Date of Award
Master of Science
Dr. Jack R. Bend
Dr. Michael J. Rieder
The formation and disposition of sulfamethoxazole hydroxylamine (SMX-HA), a metabolite of sulfamethoxazole (SMX), plays a critical role in the pathogenesis of adverse drug reactions (ADRs), and can generate cellular oxidative and nitrosative stress by forming reactive oxygen and nitrogen species (ROS/RNS). We investigated the potential attenuation of oxidative and nitrosative stress-mediated ADRs by baicalein, crocetin, resveratrol and schisanhenol alone and in combination using Jurkat £6.1 cells. These compounds are presented in herbs used as Traditional Chinese Medicine (TCM). Our results show that SMX-HA causes cell damage mediated by ROS/RNS. Low micromolar concentrations of these four chemicals attenuate SMX-HA-mediated LDH release, lipid hydroperoxide formation and carbonylated protein formation, as well as the formation of protein mixed disulfides, endpoints indicative of cytotoxicity. Treatment of cells with equimolar mixtures of these four phytochemical antioxidants was more protective of disulphide formation induced by SMX-HA., suggesting that defined mixtures of pure TCM constituents may better protect against oxidative and nitrosative stress than single chemicals in vivo.
Zhang, Lei, "ATTENUATION OF OXIDATIVE AND NITROSATIVE STRESS BY PURE CONSTITUENTS OF TRADITIONAL CHINESE REMEDIES" (2011). Digitized Theses. 3263.