Research On The Inhibitors Of Deoxyguanosine Hydroxylation Induced By Peroxynitrite

Since it was found that hydroxyl radical and nitrogen dioxide combine to form peroxynitrous acid in stratosphere, peroxynitrite has come to the wide attention in the field of Environment Science. Peroxynitrite, as a strong oxidant, causes nitration of protein, oxidation of lipid and damage of DNA. Peroxynitrite is automatically formed in nerve, macrophage and endothelium cells, and it is also produced in a variety of pathophysiological conditions such as acute, chronic inflammation, arteriosclerosis and reperfusion of ischemic organs. DNA damage induced by peroxynitrite had been observed at certain conditions. Two forms of DNA damage caused by peroxynitrite are DNA base modification and DNA single strand breakage. Deoxyguanosine reacts rapidly with peroxynitrite to form the modified product 8-hydroxy-2'-deoxyguanosine (8-OHdG). 8-OHdG can induce base mispairing and gene mutation that is carcinogenic. Some inhibitors can decrease DNA damage induced by peroxynitrite. Therefore, it is important to study these inhibitors which decreased diseases caused by peroxynitrite. Due to the instability of peroxynitrite, it isn't sold. After comparing with many synthetic methods and storage test, this paper adopt the method which synthesizes peroxynitrite in a two-phase system using isoamyl nitrite and hydrogen peroxide, and improves on the dispose of hydrogen peroxide with power MnO2. It discussed the effects of experimental conditions such as temperature and reaction time on peroxynitrite concentration. The experiment suggested that the concentration of peroxynitrite was about 0.34mol/L under optimal conditions, and the decomposition ratio of hydrogen peroxide was 95.49%. This paper simulated physiological condition( pH=7.4, 37℃) to study the reaction of deoxyguanosine and peroxynitrite. 8-nitroguanosine and 8-OHdG are formed from this reaction, and 8-OHdG is a biomarker of DNA oxidative damage. The observations showed the dependence of deoxyguanosine modification upon the concertration of peroxynitrite. Exposure to 0-2.5mmol/L of peroxynitrite resulted in a significant increase in the modified product of deoxyguanosine 8-OHdG. Finally, this paper assessed the inhibitory effects of quercetin, flavone, α-naphthoflavone, caffeic acid, vitamin C, L-glutathione, lipoic acid. These results...