**5.4 Generation of oxygen-free radicals**

Among the often-discussed mechanisms, superoxide and other reactive oxygen species (ROS) have been discussed to be an aggravating factor for CIN. Oxygen free radicals are endogenously produced, and levels can increase during oxidative stress. The commonest oxygen radicals are superoxide (O2 − ), hydrogen peroxide (H2O2), and hydroxyl radical (OH<sup>−</sup> ) [58]. O2 − and OH− are more reactive in comparison with H2O2, which is not a radical but shows greater membrane permeability. O2 − rapidly scavenges nitric oxide (NO) and could diminish NO activity in the renal vessels. Since NO decreases oxygen consumption, it is considerable to speculate that decreased (scavenged) NO levels in diabetes increases oxygen consumption, thus leading to reduced partial oxygen pressure values with consequences for endothelial-epithelial structure and function. ROS can play a role in the effects of various vasoconstrictors that are considered necessary for the development of CIN. Because ROS are extracellular signaling molecules, they can have a crucial role in mediating the effects of vasoconstrictors, such as thromboxane A2, angiotensin II, adenosine, endothelin (ET)-1, and norepinephrine. The adverse effects of CM on kidney function can therefore involve the generation of ROS, for example, via adenosine formation. This idea is supported by experiments in which the generation of ROS was inhibited by allopurinol or the amount of ROS was decreased by O2 − dismutase. In these models, CM-induced reductions in glomerular filtration rate are attenuated [59].
