Coenzyme Q10 was discovered as an essential cofactor of mitochondrial ATP production in 1957. Coenzyme Q10 is ubiquitously present in other biomembranes and even in lipoproteins. Reduced form of coenzyme Q10 (ubiquinol-10) is believed to work as antioxidant in these places. When human plasma was incubated under aerobic conditions, ubiquinol-10 depleted after the depletion of ascorbate but α-tocopherol remained unchanged, indicating that ascorbate and ubiquinol-10 are front-line antioxidants against oxygen radicals. The redox status of plasma coenzyme Q10 is a good indicator of oxidative stress since oxidative stress is defined as a disturbance in the prooxidant-antioxidant balance in favor of the former. We therefore developed a simple and reliable method for the simultaneous detection of both oxidized and reduced forms of coenzyme Q10. We applied this method to patients plasma and demonstrated an increase of oxidative stress in patient's with hepatitis, cirrhosis, and hepatoma, in LEC rats (animal model of liver cancer), in newborn babies, in patients with Parkinson disease, and others.
Helicobacter pylori (H. pylori)-infection leads to gastric cancer in human and rodents. The key determinants of this outcome are the severity and distribution of the H. pylori-induced inflammation. Bacteria or their products trigger this inflammatory process and the main mediators are cytokines. Identification of both host- and bacterial-factors that mediate is an intense area of interest in current researches. It has been demonstrated that oxidative and nitrosative stress associated with inflammation plays an important role in gastric carcinogenesis as a mediator of carcinogenic compound formation, DNA damage, and cell proliferation. Genetic information regulating such stress would be one of the host factors determining the outcome—particularly when the outcome is gastric cancer—of H. pylori infection, and the compound that attenuates such stress may be a candidate for use in chemoprevention. This review highlights recent advances in understanding of the mechanisms underlying gastric carcinogenesis following infection with H. pylori.
Tetrahydrobiopterin (BH4) prevented an increase in the formation of 8-hydroxydeoxyguanosine (8-OHdG) in calf thymus DNA by the peroxynitrite (ONOO-) or Fe2+ + hydrogen peroxide (H2O2) system. But, the addition of BH4 to the Cu2+ + ascorbic acid (AsA) system caused a very large increase in base damage. Without the addition of AsA (in the presence of Cu2+ alone), BH4 could also induce 8-OHdG formation. Experiments utilizing the Cu+ chelator bathocuproine, catalase and superoxide dismutase revealed that Cu+ and H2O2 intermediates relate to Cu2+ + BH4-induced 8-OHdG formation. Electron spin resonance experiments also showed that the hydroxyl radical is not a major intermediate. These results suggest that although BH4 is known to prevent oxidative damage in proteins and lipids, it has the potential to cause oxidative DNA damage depending on the existence of copper ions.