The salivary peroxidase system is composed of the enzyme salivary peroxidase, thiocyanate anion, and hydrogen peroxide. The system has a dual function in the oral cavity; it generates antibacterial agent, hypothiocyanite anion, and detoxifies hydrogen peroxide. For the system to function all the components are required. Previous study on the analysis of salivary components of leukemia patients undergoing chemotherapy has shown that the concentration of salivary thiocyanate is drastically reduced in these patients. Based on these observations we hypothesized that reduction of thiocyanate- in saliva may cause elevated concentrations of hydrogen peroxide and its metabolites and these substances may contribute to oral complications and mucosal tissue injury seen in these patients. It is also important to note that under certain conditions low concentrations of active oxygen species are mitogenic. Hydrogen peroxide is essential for the function of the salivary peroxidase system, however, optimal concentrations, formation in the gland, secretion, as well as the physiological role hydrogen peroxide in salivary gland cells are not known. In the present application, under the auspices of Small Grant program, three specific alms are proposed to gain further information regarding the potential significance of hydrogen peroxide in saliva and salivary glands. Methods have been developed to localize and quantitate hydrogen peroxide synthesized by salivary gland cells. Several protocols are proposed to study the mechanism by which the salivary gland cells respond to oxidative stress. Finally molecular studies will be conducted to study the effects of hydrogen peroxide on transcriptional activities of the early response genes c-fos, c-jun, and egr-1. The information which is expected from the limited study will help us to understand the protective mechanisms against oxidant stress in salivary gland cells as well as in saliva. Results obtained from this study will provide sufficient preliminary results for a future planned R01 application.
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