Figure 1.

Generation of reactive oxygen species (ROS) in the cell. ROS are generated by enzymatic and non-enzymatic redox reactions during cellular metabolism under normal and pathological conditions. Mitochondria, plasma membrane, peroxisomes, and cytosol first generate the superoxide anion (O₂•−), which becomes the precursor free radical for the generation of other ROS molecules. Cytosolic CuZN superoxide dismutase (SOD) and mitochondrial MnSOD, which are expressed in the kidney, dismutate O₂•− to H₂O₂, which yields highly reactive hydroxyl radicals (OH•) by interaction with reduced transition metal ions (such as Fe and Cu) in a Fenton reaction. In addition to ROS, cells also generate reactive nitrogen species (RNS). The major RNS include nitric oxide (•NO), peroxynitrite (ONOO⁻), and nitrogen dioxide (•NO₂). Nitric oxide (•NO) is produced by three isoforms of nitric oxide synthase (NOS), all of which are expressed in the kidney. ROS produced cause oxidative damage, including DNA damage, lipid and protein oxidation, protein nitration, and mitochondrial dysfunction.