Reactive Oxygen Species Generated by Depletion of Cellular Glutathione Mediate Cadmium Cytotoxicity
Date of Award
Master of Science
Dr. Susan R. Stapleton
Dr. David Reinhold
Dr. Alexander J. Enyedi
Masters Thesis-Open Access
Studies were put forth to test whether or not reactive oxygen species, which are influenced by the cellular level of reduced glutathione, mediate the toxicity of cadmium. Cadmium has been a focal point in the health care community in the past few years because it has been shown to induce the development of tumors, interfere with cellular signaling, and cause damage to organs, tissues, and biomolecules. Although various studies and theories have been proposed, little direct evidence, especially from studies utilizing primary cells in culture, has accumulated to show the mechanism by which the cadmium induced toxicity occurs.
Our studies show that cadmium decreases the level of glutathione in primary rat hepatocytes in a time and concentration dependent manner. In the presence of cadmium, increases in the cytotoxic parameters, lactate dehydrogenase leakage and lipid peroxidation, were observed indicating the presence of oxidative stress. Interestingly, the decrease in the level of cellular glutathione occurred at a time point prior to the observation of cadmium cytotoxicity. Furthermore, the induction of the cytotoxic parameters by cadmium was significantly blocked by various antioxidants. These results suggest that reactive oxygen species, which are generated by depleting cellular glutathione, may play an important role in various cellular events induced by cadmium.
Xu, Jun, "Reactive Oxygen Species Generated by Depletion of Cellular Glutathione Mediate Cadmium Cytotoxicity" (1999). Masters Theses. 4573.