Alterations of Antioxidant Enzymes and Biomarkers of Nitro-oxidative Stress in Tissues of Bladder Cancer

Figure 2

Formation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) and antioxidant mechanism. Superoxide generated by NADPH oxidase complex and other different pathways may be degraded by cytosolic superoxide dismutase (SOD) and by the mitochondrial manganese-containing SOD (MnSOD) to H₂O₂. H₂O₂ is further eliminated by catalase (CAT) and glutathione peroxidase (GTPx) enzymes. Hydrogen peroxide is produced also by the dual oxidase complex (Duox). H₂O₂ is able to cross cell membranes, and within the cells, it can react with Cu⁺/Fe²⁺ to form hydroxyl radicals via Fenton reaction. Nitric oxide is generated from inducible nitric oxide (iNOS). From reaction between superoxides with nitric oxide, peroxynitrite (ONOO⁻) is formed. Peroxynitrite (ONOO⁻) can damage a wide array of molecules in cells, including DNA and proteins. Reactive oxygen species (ROS) may either react directly with some amino acid residues or lead to the oxidative cleavage of the protein backbone. Other possible formation routes of protein oxidation are via the oxidation of lipids resulting in reactive molecules which react with amino acid residues and thus introduce carbonyl groups. Paraoxonase-1 (PON1) protects lipoproteins and membrane lipid from oxidative stress. Reaction of hydroxyl radicals (HO^·) with guanine residues of DNA contributes to DNA oxidation. If not repaired, this oxidative damage can cause mutations and/or altered gene transcription.